LOXHD1 SNPs: Difference between revisions

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'''See also:''' [[USH2A_SNPs|Usher: USH2A]] | [[CDH23_SNPs|Usher: CDH23]] | [[Opsin_evolution:_RBP3_%28IRBP%29|RBP3 (IRBP)]] | [[Opsin_evolution:_RPE65|RPE65]] | [[Opsin_evolution:_transducins|Transducins]]
=== Introduction ===
=== Introduction ===


[[Image:Loxhd1OHC.jpg|left]]
[[Image:LoxConcat.jpg|left]][[Image:Loxhd1OHC.jpg|right]]
LOXHD1, a large mis-annotated gene on chromosome 18 consisting solely of concatenated 120-residue PLAT domains (also seen in polycystin/lipoxygenase/alpha-toxin proteins), recently [http://www.ncbi.nlm.nih.gov/pubmed/19732867? surfaced] as a causative gene for presbycusis or age-progressive postlingual non-syndromic hearing loss type DFNB77. MYO3 (myosin IIIA) and DFNB59 (protein product pejvakin -- echo in Persian) are the only other genes to date with this autosomal recessive progressive phenotype.  
LOXHD1, a large mis-annotated autosomal gene consisting solely of 16 concatenated 120-residue PLAT domains (named for <font color="magenta">p</font>olycystin/<font color="magenta">l</font>ipoxygenase/<font color="magenta">a</font>lpha-<font color="magenta">t</font>oxins), recently [http://www.ncbi.nlm.nih.gov/pubmed/19732867? surfaced] as a causative gene for age-progressive postlingual non-syndromic hearing loss type DFNB77. Of nearly a hundred known deafness genes, only MYO3 (myosin IIIA) and DFNB59 (protein product pejvakin -- echo in Persian) share this autosomal recessive progressive phenotype.  


There is no evidence suggesting that the three encoded proteins physically interact within auditory hair cells or could cause digenic disease (as perhapss seen in the Usher Syndrome complex). Perhaps with larger numbers of pedigrees, these conditions might exhibit syndromic effects (eg on vision or kidney function as well). LOXDH1 is specific to hair cell stereocilia within the cochlea but is also expressed in testis and placenta and other cell types (not including retina or RPE to date).
Howver there is no evidence to suggest that the three encoded proteins physically interact within auditory hair cells nor that heterozygotic combinations give rise to digenic disease (as argued in Usher Syndrome). Further, with larger numbers of pedigrees, each might exhibit syndromic effects (eg affect vision or kidney function).  


Effects are not seen during development but rather in mature stereocilia which degenerate over time. LOXDH1 binds to the inner plasma membrane of stereocilia, perhaps organizing protein binding there. As with other concatenated domain proteins such as [[CDH23_SNPs|CDC23]] and [[USH2A_SNPs|USH2A]], subtle dysfunction in one of many internally repeated domains evidently cannot be compensated for by the others. Here the mouse I1342N disrupts the hydrophobic pocket between two beta sheets of the tenth PLAT domain but the protein is still made and localized properly. The first morphological change is observed at day 21: fused stereocilia and membrane ruffling at the apical hair cell surface in the basal cochlear turn. Secondary effects arise later and include damage to spiral ganglion neurons.
Mouse knockouts have not been studied; delicate auditory hair cells may just be exquisitely sensitive detectors of subtle disruptions of gene function. While LOXDH1 is specific to hair cell stereocilia within the cochlea, GenBank transcripts also imply expression somewhere within testis, placenta, hippocampus, cerebellum cortex, medulla, stomach, liver, lung, and bone marrow. The protein has not been ultrastructurally localized in any of these other tissues.
[[Image:LoxHippocampus.jpg|center]]
Some of these transcripts are exon-skipping, for example AK302484 disables the 12th PLAT domain though retains downstream reading frame. It's unclear whether such transcripts are functional or just splicing error inevitable in a giant protein (41 exons, 2273 amino acids) and merely destined for immediate turnover. The skipped exon, LGHDGASPESCWLVEELCLAVPTQGTKYML NCNCWLAKDRGDGITSRVFDLLDAMVVNIGVK, is still 72% conserved from human to shark; nothing other than functionality could explain such conservation.


The one known human allele R670* would eliminate all but the first five PLAT domains (of 16 total), possibly producing a normal but shortened protein in contrast to mouse, but might not produce protein at all due to nonsense-mediated decay. These individuals do not experience tinnitus, balance problems or vertigo, suggesting normal vestibular function even though LOXHD1 is expressed there too.
Mutations do not surface during cochlear development but rather in mature stereocilia, which degenerate over time. LOXDH1 binds to the inner plasma membrane of stereocilia, perhaps organizing protein binding there or stabilizing some aspect of the membrane. As with other concatenated domain proteins (see [[CDH23_SNPs|CDC23]] and [[USH2A_SNPs|USH2A]], subtle dysfunction in one of many internally repeated domains surprisingly cannot be compensated for by the remaining intact domains.  


One difference between cochlear and vestibular hair cells is retention of the apical kinocilium in the latter. This is lost in developing cochlear hair cells as stereocilia mature. This correlates with peak LOXHD1 expression, suggesting to Grillet et al that LOXDHY might help stabilize the stereociliary bundle in the absence of kinocilium.
Here the mouse I1342N disrupts the hydrophobic pocket between two beta sheets of the tenth PLAT domain but the protein is still made and localized properly. The first morphological change is observed at mouse day 21: fused stereocilia and membrane ruffling at the apical hair cell surface in the basal cochlear turn. Secondary effects arise later and include damage to spiral ganglion neurons.


The kinocilium is a non-motile cilium-like structure present in the crista ampullaris of the semicircular ducts and the sensory maculae of the utricle and saccule but not in the cochlear duct organ of Corti (where they degenerate following maturation of the stereociliary bundle).  
Human allele R670* would eliminate all but the first five PLAT domains (of 16 total), possibly producing a normal but shortened protein, but might not produce protein at all due to nonsense-mediated decay. These individuals do not experience tinnitus, balance problems or vertigo, suggesting normal vestibular function even though LOXHD1 is expressed there too.


Since retinal receptor cells are modified cilia and LOXDH1 acts in hair cells after the kinocilium is gone, a syndromic effect is not expected based on kinocilium/photoreceptor homologization.
One difference between cochlear and vestibular hair cells is retention of the apical kinocilium in the latter. This is lost in developing cochlear hair cells as stereocilia mature. This correlates with peak LOXHD1 expression, suggesting to [http://www.ncbi.nlm.nih.gov/pubmed/19732867? Grillet et al] that LOXDH1 might help stabilize the stereociliary bundle in the absence of kinocilium.  


Recall the kinocilium is a non-motile cilium-like structure present in the crista ampullaris of the semicircular ducts and the sensory maculae of the utricle and saccule but not in the cochlear duct organ of Corti (where in mammals it degenerates following maturation of the stereociliary bundle). Since retinal receptor cells are modified cilia and LOXDH1 functions most critically in microvillar hair cells after the kinocilium is gone, a syndromic effect extending to vision would not arise based on kinocilium/photoreceptor cilia homologization.
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=== Phylogenetic occurence ===
=== Phylogenetic occurence ===


The PLAT domain is quite ancient, readily tracing back to prokaryotes. However in other proteins it occurs only as single copy, often in conjunction with one or more catalytic domains. A common denominator of PLAT domain proteins is their association with lipid or membrane metabolism. This is perhaps mediated by extruded tryptophans which extend out from the standard beta barrel surface.
The PLAT domain is quite ancient, readily tracing back to prokaryotes. However in other proteins it occurs only as single copy, often in conjunction with one or more catalytic domains. A common denominator in PLAT domain proteins is their association with lipid or membrane metabolism. This is perhaps mediated by extruded tryptophans which extend out from the standard beta barrel surface.
 
LOXHD1 itself has highly conserved orthologs throughout vertebrates, indeed deuterostomes (though the Branchiostoma gene model XM_002606291 contains other domains). These species all contain mechanosensory cells with ciliary F-actin based protrusions though expression has not be localized outside of mammals. No counterparts of the gene can be found in Ecdysozoa (strictly non-cilary mechanosensation) yet lophotrochozoa (Schistosoma and likely Aplysia)  have full length counterparts, as can cnidrians (Hydra, Nematostella) though gene models at this time are fragmentary.
 
This establishes gene loss in the ancestral ecdysozoan, rather than gene innovation in Bilatera. However the overall impression is phylogenetically spotty occurence outside of deuterostomes. It's unclear whether some other gene product can compensate for lost LOXHD1 or whether it simply does not play an essential role.
 
Most surprisingly, full length orthologs of LOXHD1 with 17 PLAT domains and very similar intronation patterns are readily recoverable from early eukaryote genomes, notably Trichoplax and the choanflagellate Monosiga. This seems to rule out an obligatory association with F-actin-based mechanosensory organelles as the basal metazoan Trichoplax exhibits only 4 distinct cell types and the early animal Monosiga is unicellular.
 
Thus LOXDH1 is not even a metazoan innovation. Lateral gene transfer makes no sense in this context and is contradicted by the gene tree. The extraordinary conservation Monosiga to human -- surely in the 95th percentile of all genes -- establishes a long-selected intracellular role.
 
In the plant world, occurence is restricted to Chlamydomonas and Micromonas proteins (XM_001703369, XM_002502455) with 20 PLAT domains and numerous WD40 domains (ie not necessarily orthologous to animal pure poly-PLAT proteins). A curious note on the Chlamydomonas genbank entry states "identified by comparative genomics as being present only in organisms having motile cilia." Vertebrate kinocillia are non-motile.
 
Within deuterostomes, the large length of the gene does not sit well with gappy, incomplete and sometimes chaotic assemblies. Chicken, lamprey, amphioxus, tunicate and sea urchin are among the many that do not yield satisfactory full length gene models, in part because transcript support is limited to small regions of large proteins. However these species do contain long poly-PLAT proteins orthologous to human LOXHD1 (based on consecutive domains having consecutive best-blast).
 
Some of these unreliable sequences are provided in the reference sequence compilation below. Ironically, the obscure Monosiga and Trichoplax have better assemblies and more accurate gene models presumably because their genomes are much smaller.
 
Thus within vertebrates it is only feasible to compare selected PLAT motifs. Here there is a risk of using best-blast because significant cross-over matches will occur to other PLAT domains within the same protein, so some additional signature must be used for validation.


LOXHD1 itself has highly conserved orthologs throughout vertebrates, indeed deuterostomes (though the Branchiostoma gene model XM_002606291 contains other domains). These species all contain mechanosensory cells with ciliary F-actin based protrusions. No counterparts of the gene can be found in Ecdysozoa (strictly non-cilary mechanosensation) yet lophotrochozoa (Schistosoma, and perhaps Aplysia) can have full length counterparts, as can cnidrians (Hydra, Nematostella) though gene models here seem fragmentary.
=== PLAT domain structure ===


This establishes gene loss in the ancestral ecdysozoan, rather than gene innovation in Bilatera. However the overall impression is phylogenetically spotty occurence outside of deuterostomes. It's unclear whether some other gene product can compensate for lost LOXHD1 or whether it does not play a central role.
The structure of three proteins containing single PLAT domains have been determined. The best blastp of human LOXHD1 to these is a coral lipoxygenase/allene oxidase natural fusion protein with PDB accession [http://www.jbc.org/cgi/pmidlookup?view=long&pmid=16162493 3DY5]. Lower quality but still useful matches occur with RAB6 (accession [http://www.ncbi.nlm.nih.gov/pubmed/19141279 3CWZ]) and rabbit reticulocyte lipoxygenase (accession [http://www.ncbi.nlm.nih.gov/pubmed/9406550 2P0MA]).  


Most surprisingly, full length orthologs of LOXHD1 with 16 PLAT domains and very similar intronation patterns are readily recoverable from early eukaryote genomes, notably Trichoplax and the choanflagellate Monosiga. This seems to rule out an obligatory association with F-actin-based mechanosensory organelles as the basal metazoan Trichoplax exhibits only 4 distinct cell types and the early animal Monosiga is unicellular. This rules out LOXDH1 as a metazoan innovation. Lateral gene transfer makes no sense in this context and is contradicted by the gene tree. The extraordinary conservation Monosiga to human -- surely in the 95th percentile of all genes -- suggests conservation of some fundamental intracellular role.
The basic structure of a PLAT domain consists of a sandwich of two 2-stranded beta sheets (beta barrel). The lipoxygenases are calcium-binding via extended pairs of acid residues and have conserved hydrophobic residues likely inserting into the plasma membrane but neither these nor the hydrophobic residues are conserved in LOXHD1.


In the plant world, Chlamydomonas and Micromonas have proteins (XM_001703369, XM_002502455) with 20 PLAT domains and numerous WD40 domains (ie are not necessarily orthologous to animal pure poly-PLAT proteins). A curious note on the genbank entry states "identified by comparative genomics as being present only in organisms having motile cilia."
The independently folding PLAT domain is sometimes denoted as LH2 or [http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9632630 'C2-like'] depending on the structural publication and domain tool. This introduces confusion because SMART/Pfam/InterPro utilize very distinct HMM models for C2 and PLAT/LH2.


Within deuterostomes, the large length of the gene does not sit well with gappy, incomplete and sometimes chaotic assemblies. Chicken, lamprey, amphioxus, tunicate and sea urchin are among the many that do not yield satisfactory full length gene models, in part because transcript support is spotty. However these species do contain long poly-PLAT proteins no doubt orthologous to human LOXHD1. Some of these unreliable sequences are provided in the reference sequence compilation below. Ironically, the obscure Monosiga and Trichoplax have better assemblies and more accurate gene models presumably because their genomes are much smaller.
The secondary structure here is so generic that convergent evolution (non-homologous origins) must be considered, as with TIM proteins. Here however significant blastp matches at the primary sequence level unify PLAT and LH2 sequences to the exclusion of the entire C2 family. This agreement cannot have originated repeatedly by chance given the vast combinatorial space available to amino acid sequences.  


Thus within vertebrates it is only feasible to compare selected PLAT motifs that fall with an exon or two. Here there is a risk of using best-blast because many cross-ove matches will occur to other PLAT domains within the same protein, so some additional signature must be used.
Further, all PLAT/LH2 domains share characteristic conserved residues. Thus PLAT and LH2 domains are in fact all homologous (descended from a single source) and so multiplicity of domain names is inappropriate. PLAT is used here rather than LH2 (<font color ="red">l</font>ipoxygenase <font color ="red">h</font>omology) because the former is a more comprehensive acronym of protein classes containing the domain (lacking only lipases).  


=== 3D Structure ===
[http://www.jbc.org/content/273/26/15879.long#ref-2 C2 domains] bear an uncertain relationship to PLAT domains because a resemblance occurs only at the secondary and tertiary structural levels. The lack of convincing blastp of HMM profile matches could be due either to extreme divergence of primary sequence or to convergent evolution resulting in the same basic fold (and perhaps a similarly convergent hydrophobic intermediating function). If ever homologous, PLAT and C2 diverged in prokaryotic times.


The structure of three proteins containing single PLAT domains have been determined. The best blastp of LOXHD1 to these is a coral lipoxygenase called allene oxide synthase 8r-lipoxygenase with PDB accession 3DY5. Lower quality but still useful matches occur with RAB6 (accession CWZ) and rabbit reticulocyte lipoxygenase (accession). The basic structure consists of a sandwich of two 2-stranded beta sheets (beta barrel) with certain conserved hydrophobic residues reaching out to the membrane. The lipoxygenases are calcium-binding via extended acid residues but neither these nor the hydrophobic residues are conserved in LOXHD1.
The name C2 implies calcium binding yet even here some C2 domains function independently of calcium. It isnot clear whether calcium binding is ancestral or derived. If ancestral, it has not been resolved whether binding has been lost once or multiple times in different regions of the domain tree. While PLAT domains can be structurally aligned to C2 domains, that is potentially misleading and unnecessary given three determined structures for bona fide PLAT domains.  


The PLAT domain is sometimes denoted as LH2 or C2 depending on the publication and domain tool (eg Pfam or SMART). The secondary structure is so simple that convergent evolution (independent origins) must be considered, as with TIM proteins. Here however significant blastp matches at the primary sequence level cannot have originated repeatedly by chance given the vast combinatorial space available to amino acid sequences. Further, all PLAT/LH2/C2 domains share characteristic conserved residues. Thus these domains are in fact homologous (descended from a single source) and the multiplicity of domain names is inappropriate. PLAT is used here because it is an acronym of all protein classes containing the domain.
LOXHD1, which tracks back to the earliest unicellular animals, lacks capacity for calcium binding in all 16 of its domains in all descendant clades based on non-conservation of acidic liganding residues relative to coral lipoxygenase, human LOX5 and clostridial alpha-toxin PLAT domains.
 
[[Image:AlleneLox.jpg]]
 
=== PLAT domain evolutionary history ===
[[Image:LoxDomainTree.jpg|left]]
The human genome contains 20 other  proteins with significant blastp matching to the PLAT domain of LOXHD1. These are shown below along with their flanking domains (GPS, RUN etc). After adjusting for gene expansions (paralogy), only 4 classes occur: polycystins, lipoxygenases, lipases, and RAB6-interacting. These all contain a single PLAT domain. The final column shows its best-blastp to LOXHD1; no strong pattern emerges though perhaps PLAT:09 may conserve the most ancestral features and PLAT:15 the least.
 
The first two columns at bottom shows the blastp score of a given human LOXHD1 PLAT domain averaged over it match to the 12 other genes; the second two columns show the average match of other genes over the 16 LOXHD1 PLAT domains.
 
The domain tree thus looks like ((((LOXHD1,RAB6Is),polycystins),lipoxygenases),lipases). A possible parsimonious evolutionary scenario postulates a single standalone PLAT domain originally serving as an auxillary protein to various enzymes with hydrophobic substrates. Later, copies fused with these catalytic domains in separate events with gain in efficiency.
[[Image:PLATrates.jpg|left]]
Observe the PLAT domain is N-terminal to the catalytic domain of lipoxygenases but C-terminal to it in lipases and sandwiched internally by a repeated domain in RAB6I, indicating three separate fusion events. These fusion proteins then expanded copy number to the small paralogous gene families seen today. The individual PLAT domains then evolved at different rates, though they continued to share some common constraints (beta barrel, membrane fingers).
 
The standalone gene eventually expanded to a poly-PLAT protein; today the standalone domain itself is gone (no longer represented in extant species). It is not easy to discern intermediate events: each species seems to generate a unique internal domain tree (above). In other words, individual PLAT domains may have evolved at different rates in different clades, obscuring initial relationships from order of duplication.
 
Intermediate events may have included 1 domain tandemly duplicating to 2 and then to 4, 8, and finally 16 but other scenarios involving inhomogeneous recombination (and even higher multiplicities) are equally plausible. However the number of repeats has been very stable over many billions of years of branch length; each individual repeat seems important too in view of known point mutations.
[[Image:LoxTrees.jpg|center]]
<font color ="blue">PKD1L1  GPS-TM-PLAT-TM  chr07:47780815  polycystin 1-like 1          pdb:3CWZ  PLAT:14 36%
PKD1    GPS-TM-PLAT-TM  chr16: 2078712  polycystin 1                  pdb:3CWZ  PLAT:01 38%
PKD1L2  GPS-TM-PLAT-TM  chr16:79691985  polycystin 1-like 2 signal    pdb:3CWZ  PLAT:11 35%
PKD1L3  GPS-TM-PLAT-TM  chr16:70556160  polycystic kidney disease    pdb:3CWZ  PLAT:01 40%
PKDREJ  GPS-TM-PLAT-TM  chr22:45030224  receptor egg jelly signal    pdb:3CWZ  PLAT:11 32%</font>
<font color ="brown">DENND5A  RUN-PLAT-RUN    chr11: 9116949  RAB6 interacting 1            pdb:3CWZ  PLAT:09 42%
DENND5B  RUN-PLAT-RUN    chr12:31426424  RAB6 interacting 2            pdb:3CWZ  PLAT:09 37%</font>
<font color ="green">ALOX5    NH2-PLAT-lipox  chr10:45189635  arachidonate 5-lipoxygenase  pdb:2P0M  PLAT:01 37%
ALOX15      PLAT-lipox  chr17: 4480963  arachidonate 15-lipoxygenase  pdb:2P0M  PLAT:03 26%
ALOX12      PLAT-lipox  chr17: 6840108  arachidonate 12-lipoxygenase  pdb:2P0M  PLAT:09 30%
ALOX15B      PLAT-lipox  chr17: 7888129  arachidonate 15-lipoxygenase  pdb:2P0M  PLAT:02 34%
ALOX12B      PLAT-lipox  chr17: 7916679  arachidonate 12R-lipoxygenase pdb:2P0M  PLAT:09 29%
ALOXE3      PLAT-lipox  chr17: 7939943  arachidonate lipoxygenase 3  pdb:2P0M  PLAT:16 32%</font>
<font color ="magenta">LIPC    LIP-PLAT        chr15:56511467  lipase C                      pdb:2P0M  PLAT:11 30%
LIPG    LIP-PLAT        chr18:45342425  endothelial lipase          pdb:2P0M  PLAT:09 32%
LPL      LIP-PLAT        chr08:19840862  lipoprotein lipase            pdb:2P0M  PLAT:11 24%
PNLIP    LIP-PLAT        chr10:118295418 pancreatic lipase             pdb:2P0M  PLAT:16 24%
PNLIPRP1 LIP-PLAT        chr10:118340480 pancreatic lipase-related 1   pdb:2P0M  PLAT:16 27%
PNLIPRP2 LIP-PLAT        chr10:118370455 pancreatic lipase-related 2  pdb:2P0M  PLAT:01 31%
PNLIPRP3 LIP-PLAT        chr10:118177414 pancreatic lipase-related 3  pdb:2P0M  PLAT:02 27%</font>
[[Image:Loxtrichmono.jpg]]


Below allPLAT domains found in human proteins are aligned with the 16 domains of human LOXHD1. The coral lipoxygenase is included because it provides the template for beta strand assignment and the problematic calcium binding sites and hydrophobic extended residues. The lower alignment is just with human LOXHD1 domains and uses an optimized seventh PLAT domain (with KE expansion removed).
Below all PLAT domains found in human proteins are aligned with the 16 domains of human LOXHD1. The coral lipoxygenase is included because it provides the template for beta strand assignment and locating the problematic calcium binding and hydrophobic extended residues. The lower alignment is just with human LOXHD1 domains and uses an optimized seventh PLAT domain (the KE expansion is removed).


[[Image:PLATalignments.jpg]]
[[Image:PLATalignments.jpg]]
[[Image:AlleneLox.jpg]]


Individual PLAT domains are quite conserved. That is illustrated by a difference alignment of the fifth PLAT domain in 40 vertebrates (human to lamprey) below. Note columns where human sequence represents a unique change -- such as H->R in column 5 -- may be minor alleles or disease variants rather than the predominate residue in the overall human population.
Individual PLAT domains can be quite conserved over the mammalian time scale. That is illustrated by a difference alignment of the fifth PLAT domain in 40 vertebrates (human to lamprey) below. Note columns where human sequence represents a unique change -- such as H->R in column 5 -- may be minor alleles or disease variants rather than the predominate residue in the overall human population.
<pre>
<pre>
 01.hg18_6  MARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPSDSSATLK
01.hg18_6  MARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPSDSSATLK
 02.panTro  ....R..............................................................................................................................
02.panTro  ....R..............................................................................................................................
 03.gorGor   S..R...........................................................................--------------------------..................G......
03.gorGor   S..R...........................................................................--------------------------..................G......
 04.ponAbe  ....R..............T.....................................................................................-....................N....
04.ponAbe  ....R..............T.....................................................................................-....................N....
 05.rheMac  ....R.........................................................................................................................N....
05.rheMac  ....R.........................................................................................................................N....
 06.calJac  ....R...........................................................K.............C...............................................N....
06.calJac  ....R...........................................................K.............C...............................................N....
 07.micMur  ....R...........................................................M.............................................................N....
07.micMur  ....R...........................................................M.............................................................N....
 08.otoGar  ....R.                                              ............K.................-..........H.P.V.......T....................N....
08.otoGar  ....R.                                             ............K.................-..........H.P.V.......T....................N....
 09.tupBel   ...R...........................................................K............A................................................N....
09.tupBel   ...R...........................................................K............A................................................N....
 10.mm9_6_  ....R...........................................................K.....V.......................................................N....
10.mm9_6_  ....R...........................................................K.....V.......................................................N....
 11.rn4_6_  ....R...........................................................K.....V........................................Q...................
11.rn4_6_  ....R...........................................................K.....V........................................Q...................
 12.dipOrd  ....R.....................Y..................E..................K.....V.......S.S.............................................N....
12.dipOrd  ....R.....................Y..................E..................K.....V.......S.S.............................................N....
 13.cavPor  ....R.......F.............Y...................................L.K.............................................................N....
13.cavPor  ....R.......F.............Y...................................L.K.............................................................N....
 14.speTri  .V..R.....................Y......-.....-------------............K............P......E...L.....................................N....
14.speTri  .V..R.....................Y......-.....-------------............K............P......E...L.....................................N....
 15.oryCun                                          ..........S.............K..........................................................TG.N....
15.oryCun                                          ..........S.............K..........................................................TG.N....
 16.ochPri  ....R...........................................................K.............S....V..........................................N....
16.ochPri  ....R...........................................................K.............S....V..........................................N....
 17.vicPac   ...R.......V.............................I.....................K.................F.E.........................................N....
17.vicPac   ...R.......V.............................I.....................K.................F.E.........................................N....
 18.turTru  ....R...........................................V...............K.....V...........F.......................---------...........N....
18.turTru  ....R...........................................V...............K.....V...........F.......................---------...........N....
 19.bosTau  ....R.....................Y.....................................K.................F.E....................-....................N....
19.bosTau  ....R.....................Y.....................................K.................F.E....................-....................N....
 20.equCab  ....R...........................................................K............A....F.E.........................................N....
20.equCab  ....R...........................................................K............A....F.E.........................................N....
 21.felCat  ....R...........................................................K............G....F.E.........................................N....
21.felCat  ....R...........................................................K............G....F.E.........................................N....
 22.canFam  ....R...........................................................K............G....F.E.........................................N....
22.canFam  ....R...........................................................K............G....F.E.........................................N....
 23.myoLuc  ...HR......D.R......S.....Y............T.K..DEM.Q...............K........T.V.G....F..................Y........................N....
23.myoLuc  ...HR......D.R......S.....Y............T.K..DEM.Q...............K........T.V.G....F..................Y........................N....
 24.pteVam   ...R.........................................M.................K..........R.G....F.E.........................................N....
24.pteVam   ...R.........................................M.................K..........R.G....F.E.........................................N....
 25.eriEur  ....R.....................Y.....................................K............G....F.A..............M..........................N....
25.eriEur  ....R.....................Y.....................................K............G....F.A..............M..........................N....
 26.loxAfr                          ..Y.......-..M.....................A..L.K............G......E.........................................N....
26.loxAfr                          ..Y.......-..M.....................A..L.K............G......E.........................................N....
 27.proCap  ....R.....................Y..A.......M...........R.........A..L.K............A......E..............M...---...................NN....
27.proCap  ....R.....................Y..A.......M...........R.........A..L.K............A......E..............M...---...................NN....
 28.echTel  ....R.....................Y..........MF.....V..............A..L.K......M.....A......-...LKK.........K..G.G....................N...R
28.echTel  ....R.....................Y..........MF.....V..............A..L.K......M.....A......-...LKK.........K..G.G....................N...R
 29.choHof  .V..R.....................Y.........W.........M....S...Y...A..L.K.K.I.VG.....GN...F.E..............M....N...AR.Q.....I......G.N....
29.choHof  .V..R.....................Y.........W.........M....S...Y...A..L.K.K.I.VG.....GN...F.E..............M....N...AR.Q.....I......G.N....
 30.monDom  ..Q.R..L...DI.....N.QAFV.....A......M.......MEICQ..........A..V.K......G.....K....F.VK..................N..F...Q..............NSR..
30.monDom  ..Q.R..L...DI.....N.QAFV.....A......M.......MEICQ..........A..V.K......G.....K....F.VK..................N..F...Q..............NSR..
 31.ornAna  IVK.R...V..D.N......R.FI..I.........I.........T.........FV.A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
31.ornAna  IVK.R...V..D.N......R.FI..I.........I.........T.........FV.A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
 32.galGal  VIK.R......MVS.S......FV..I..Q....D.V..K.I..VNK.........F..A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
32.galGal  VIK.R......MVS.S......FV..I..Q....D.V..K.I..VNK.........F..A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
 33.anoCar   IK.R...H..NVS.S....H.FA..I..Q....D.V.Q.SV.TVNK....S....I..A.NLKQ......G.....GS.....GK.I...D.....EAQ....Y.....NE....II...V.AGR.SL.E
33.anoCar   IK.R...H..NVS.S....H.FA..I..Q....D.V.Q.SV.TVNK....S....I..A.NLKQ......G.....GS.....GK.I...D.....EAQ....Y.....NE....II...V.AGR.SL.E
 34.xenTro                                   ...F.IE.K..MNK.......D.I..A..LKQ.K....G.....G.C...M.K.V...D.K..TEAI....N..F.RNE...HII...V.AGD.QN.R
34.xenTro                                   ...F.IE.K..MNK.......D.I..A..LKQ.K....G.....G.C...M.K.V...D.K..TEAI....N..F.RNE...HII...V.AGD.QN.R
 35.tetNig   LK.RI.I...NVG.G....S.F.NII..L......SMITSK..VNK.....H...L....CLGR.S...VG...R.G.C..F..K.T.........SAI....F....HNE....I....V.AGDGRLF 
35.tetNig   LK.RI.I...NVG.G....S.F.NII..L......SMITSK..VNK.....H...L....CLGR.S...VG...R.G.C..F..K.T.........SAI....F....HNE....I....V.AGDGRLF
 36.fr2_6_  LIK.R..I...NVS.G....S.F.NVI..L.......MIMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M.........SAI....F....HNE....I....V.A       
36.fr2_6_  LIK.R..I...NVS.G....S.F.NVI..L.......MIMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M.........SAI....F....HNE....I....V.A     
 37.gasAcu  LIK.R..I...NVS.S....S.F.NVI..L.......MFMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M...D.....LAT....F....RNE....I....V.AGDGRLF 
37.gasAcu  LIK.R..I...NVS.S....S.F.NVI..L.......MFMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M...D.....LAT....F....RNE....I....V.AGDGRLF
 38.oryLat   IK.R..I...TVS.S....S.F.NVI..L.......M.MSK..VNK.....H...L....WLGQ.....VG...R.G.C..F..K.M.........AAI....N....QNE....II...V.AGEG    
38.oryLat   IK.R..I...TVS.S....S.F.NVI..L.......M.MSK..VNK.....H...L....WLGQ.....VG...R.G.C..F..K.M.........AAI....N....QNE....II...V.AGEG  
 39.danRer   VK.R...Y..DVS.S....H.F...I..L....D.S.I..K..INK..R......I..A.SIGP......G...R.G.C.....K.TI.....A..QA.....S..F.RNE....I....Q.FADGRLY 
39.danRer   VK.R...Y..DVS.S....H.F...I..L....D.S.I..K..INK..R......I..A.SIGP......G...R.G.C.....K.TI.....A..QA.....S..F.RNE....I....Q.FADGRLY
 40.petMar   VK.L..IH..KHG.G......FV..Y.EQ....D.M..TS...VNK..R..V...V..C..LKR.T....G...R.GS...F..KIM.K-D.RRQCEE.....N....D.E....I....VAGGCQMLK 
40.petMar   VK.L..IH..KHG.G......FV..Y.EQ....D.M..TS...VNK..R..V...V..C..LKR.T....G...R.GS...F..KIM.K-D.RRQCEE.....N....D.E....I....VAGGCQMLK
 Consensus  ...yrvt..tg...g.gtda.v..cl.gd.gdtger.ly.crnn...fekgna...t..s.t$rk.r...!r...k.ggs..y$d.!lvre#.qpes.nv...c.r.l.k#k....l!...l.sgsnatlk
Consensus  ...yrvt..tg...g.gtda.v..cl.gd.gdtger.ly.crnn...fekgna...t..s.t$rk.r...!r...k.ggs..y$d.!lvre#.qpes.nv...c.r.l.k#k....l!...l.sgsnatlk
</pre>
</pre>
=== Expansion of the PLAT:07 domain ===
The seventh PLAT domain (human numbering) is unique domains in having a large compositionally simple expansion in the middle of the domain. It is a unique signature of the LOXHD1 orthology class that would distinguish it from other poly-PLAT domain concatenates of independent origin. That issue is completely hypothetical because no other protein in any vertebrate genome contains more than a single PLAT domain. Indeed, the LOXHD1 gene is single-copy in all species that retain it (including teleost fish). Thus even with very ancient eukaryotic divergencs, the corresponding genes can be taken as straightforward human orthologs.
Presumably a loop out of the beta barrel, the expansion consists of an extremely high AG content at the dna level and encodes charged residues, primarily lysine K and glutamate E residues. These are asymmetrically distributed with the lysines N-terminal and the glutamates distal. The region will be called the KE loop of PLAT:07 here.
Despite minimal net charge, this region may not be able to interact with (hydrophobic) membranes. Yet the split PLAT domain retains the potential to form a standard beta barrel. The seventh PLAT domain is quite variable even within mammals and must be hand-annotated to ensure accuracy (because its quasi-repetitive nature wreaks havoc with alignment). This section uses comparative genomics within eukaryotes to answer the following questions:
* when did the high GA section arise in phylogenetic time?  [early eukaryotes]
* what is its source?                                      [internal expansion, replication slippage]
* did it arise from intron or retroposon retention?        [species lacking the repeat also have a single exon]
* can the boundaries of 7th PLAT domain be better located?  [conservation on both sides of the KE region allow definition of the PLAT domain segments]
* is the 44-species alignment accurate in this region?      [corrections are needed when longer than human, eg platypus]
* does the KE domain disrupts PLAT function?                [evidently not: the split domain is highly conserved and can form a normal beta barrel]
* is it a mammalian innovation or an unwanted intrusion?    [this ancient expansion has variable expansion and contraction in different clades]
homSap LEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLRQLLKKERLKAKLQRKKKKRKGSDEEDEGEEEESSSSEESSSEEEEMEEEEEEEE  FGPGMQEVIEQHKFEAHRWLARGKEDNELVVELVPAGKPGPE 1
ornAna LEATDVGEIYKVRLGHSGEGFGSGWFIESLVLKRLVLKEVEPNPEEEKRKAKERERAREQRRKERLKAKQQRKKKKKMKKSSDDEDSEAEDSEEEEGSSEEESSSSSSEEEVEEEFGPGIKEVIDVYKFEAHRWLARDEDDKELIVELEPANRPGPE 1
galGal VEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKMDETD    KKKKKKKKKSEEEEEEEE                                                  TKVEEVMDVYTFVAHRWLAKDEGDKELVVELVPDGESELE 1
taeGut REAADVGKIYKIRIGHDGTGIGDGWFLESVTLKRLATKTEGSD    KKKKKKKKSEEEETKE                                                        EEGMDVYTFVAHRWLAKDEGDKELVVELVPDGESDLE 1
anoCar VEAVDVGKVYKIRIGHDGKGFGDGWFLDSVVVKKLPTKVP        KKKKKKKKKKTPEEEEAEE                                                    GPGIMEVYNFTPCRWLASDEEDKELVVELVPDEGSELE 1
oryLat IEALDVGKIYKIRIYHDGSGIGDGWFLETVDIKRLTMALVQVEV    KKEEAPKKDKKKDKKKKKKEEEEVEIIEE                                          MQEVVETFTFTCNRWLARDEEDGEIVVELLTEENEDLE 1
gasAcu IEAKDVGKIFKIRIGHDGSGIGSGWFLETVDVKRLILALVPKEK    KKEDKKKKKKKKEDVDEEGGEE                                                MQEVVLTYSFPCSRWLAGGEEDGELVVELLPDDAKELE 1
takRub IEAKDVGKIFKIRIGHDGLGIGSGWFLEKVYVKHLIMALVPREN    KKDDKKKKKKKKKDKEDEEEVGGEE                                              MQEVVVTYHFPCSRWLASGEDDDDLVVELLPEDAEELE 1
petMar VEAMDVGKVVKLRVGHDNSGMGSGWFLDSIVIRRLRQSSPHRPQPVDA              EEDEDEEDDEEAEDED                                            VQTYTFPCKRWLARDEDDGEIVRELLPQDCAEME 1
sacKow IEAADVAMLTKIRIGHDNSGRSAGWYLERVIIERFPPKRKM          KRKRSGTPRRRGEYDEEDYDD                                              IPETNVVNFVCNRWFAKDEEDHQIVRELLPTDEEALKGH 1
triAdh VECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKET    DEREEETAKKDADEPEKLDE                                                      NNYLFVANRWLSKEEGDRQTVIEISPVGVDGALA 1
monBre LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQAR                                                                                      IYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDN 1
=== Introns relative to PLAT domains ===
Here it emerges that PLAT domains correspond to 2-3 consecutive exons with conserved phasing, allowing for potential alternative splicing that reduced domain count while not introducing premature stop codons. This may reflect the origin of the 16 PLAT domains by iterated inhomogenous recombination. (to be continued).


=== Reference sequences (intronated) ===
=== Reference sequences (intronated) ===


The sequences below are broken into individual exons with reading phase ([[Opsin_evolution:_ancestral_introns#Intron_location_and_phase_for_dummies|codon overhang]]) indicated by 012. Alternating colors show odd and even numbered PLAT domains. The 7th domain (which contains the charged KE expansion loop in mammals) is shown in red.
The sequences below are broken into individual exons with reading phase ([[Opsin_evolution:_ancestral_introns#Intron_location_and_phase_for_dummies|codon overhang]]) indicated by 012. Alternating colors show odd and even numbered PLAT domains. The 7th domain (which contains the charged KE expansion loop in mammals) is shown in red. In some cases, the PLAT domains are numbered and exon phases are not indicated. In the case of poor quality but phylogenetically important sequences, an approximate sequence is shown.


  >LOXHD1_homSap_full 41 exons|2273 aa|chr18|span 179,559 bp|no signal peptide|no conserved cysteines|16 PLAT domains|EIW --> WNW mouse deafness
  >LOXHD1_homSap_full 41 exons|2273 aa|chr18|span 179,559 bp|no signal peptide|no conserved cysteines|16 PLAT domains|EIW --> WNW mouse deafness
Line 222: Line 314:
  2 K<span style="color: #0066CC;">ITYHLKITTANVKRAGTDCSINLQIFGTNGVTNCYILEKTSNRFAQGITDNISLEMEDVGKLLKMRIGHDNQ 0
  2 K<span style="color: #0066CC;">ITYHLKITTANVKRAGTDCSINLQIFGTNGVTNCYILEKTSNRFAQGITDNISLEMEDVGKLLKMRIGHDNQ 0
  0 GKNKHWNLSCVEVTVANTNQLYRFVYDDWLSLTYGKRKSLWADLPAM</span>IGDTVQLK 1
  0 GKNKHWNLSCVEVTVANTNQLYRFVYDDWLSLTYGKRKSLWADLPAM</span>IGDTVQLK 1
  2 ETCLD<span style="color: #996633;">IFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNS 0
  2 E<span style="color: #996633;">TCLDIFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNS 0
  0 IDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCS</span>EVYMNDSKGHRTIDQESIETLLTTADSMNISDLKDNPEGKL 1
  0 IDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCS</span>EVYMNDSKGHRTIDQESIETLLTTADSMNISDLKDNPEGKL 1
  <span style="color: #0066CC;">2 VYEVVIETGNLKDSGTTCDAWIILEGKHGRSPKLELVNQVGNPILQINQMNTFQ 2
  <span style="color: #0066CC;">2 VYEVVIETGNLKDSGTTCDAWIILEGKHGRSPKLELVNQVGNPILQINQMNTFQ 2
Line 229: Line 321:
  2 ESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVS</span>N* 0
  2 ESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVS</span>N* 0
   
   
  >Trichoplax adhaerens (trichoplax) Metazoa XM_002107971 17 PLAT domains [http://www.ncbi.nlm.nih.gov//genomes/geblast.cgi?bact=off&gi=6008 blast]
  >LOXHD1_triAdh Trichoplax adhaerens (trichoplax) Metazoa XM_002107971 17 PLAT domains [http://www.ncbi.nlm.nih.gov//genomes/geblast.cgi?bact=off&gi=6008 blast]
  0 MSASLAMQELMSDPSGHFAPKPPPGRSKINRKRPQT 1
  0 MSASLAMQELMSDPSGHFAPKPPPGRSKINRKRPQT 1
  2 APGRQITTASKAPKLWRSSTYNEPNLKRRKFIVTLNHKKDISSISRNAPYANRAYTTAMATAARTYSNALNKGQQKEIIPIYNPLCDPHLNDYYARKFGLLNSRD 0
  2 APGRQITTASKAPKLWRSSTYNEPNLKRRKFIVTLNHKKDISSISRNAPYANRAYTTAMATAARTYSNALNKGQQKEIIPIYNPLCDPHLNDYYARKFGLLNSRD 0
Line 264: Line 356:
  2 ASFRSNSTDLGEMVSASGRRASSRKGPVMAPIDEK 1
  2 ASFRSNSTDLGEMVSASGRRASSRKGPVMAPIDEK 1
  2 CVPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVS 1
  2 CVPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVS 1
  2 HNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAANAQVTSYTA 1  
  2 HNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAANAQVTSYTKPYELTIHTGDVQNA 1  
  2 GTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIP 0
  2 GTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIP 0
  0 LELDDVGTIKKIRIGHDGKGSRTDWYLEK 0
  0 LELDDVGTIKKIRIGHDGKGSRTDWYLEK 0
Line 274: Line 366:
  2 ELKPVKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* 0
  2 ELKPVKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* 0
   
   
  >Monosiga brevicollis (monosiga) Eukaryota|Choanoflagellates  XM_001742822 15 PLAT domains
  <span style="color: #0066CC;">>LOXHD1_triAdh Trichoplax adhaerens (trichoplax) Metazoa XM_002107971 17 PLAT domains [http://www.ncbi.nlm.nih.gov//genomes/geblast.cgi?bact=off&gi=6008 blast]
  MADLPVPTTALQRLQLERSRYSFAAADPPPSFVQRYTSADVLSHRLYAQGLASDVGPGSHSSLGMSRRVELPPYNPLNDPALANYFARKFEWNSTRSVGA
    MSASLAMQELMSDPSGHFAPKPPPGRSKINRKRPQT<span style="color: #996633;">APGRQITTASKAPKLWRSSTYNEPNLKRRKFIVTLNHKKDISSISRNAPYANRAYTTAMATAARTYSNALNKGQQKEIIPIYNPLCDPHLNDYYARKFGLLNSRD</span>ESRKNRKQ<span style="color: #996633;">AG
  GSGSRRSASASLTRTRQPVRGASAHGHTKSRTKSSHRKGHASLEIFTSKRSNPVSKSEKYITVVGTKGRSDAIQLAAPGVHFRAGNKDVFQVNLTGIGKP
  01 VAYQFGVKTGDKKGSDTDA</span>VYIQVIGTKDKIPKKRLFKKQETEKTERGNLFKFDKSTVEKFAVQHRDIGDPVKLIVE<span style="color: #996633;">HDGNEKRHGWFLEEITLTNIQSKKSWLFPCHKWLSKYEGDRKLCYE LKPLAKAGK
  TKVILENTGTKRTDGWCVSKVVLVKKTDKGTRRYRFSGPVWLSKHHDEMKLKRVLHIDDEDIGSGNGYRIDCYTGDVANAGTDAVATIQLFGSKGQSPMV
  02 A</span>VYEVSVLTGDKRGAGTDANVSVTLFGKHTSSPKIQLLKS<span style="color: #996633;">SKHKNPFERNNTDEFKIRTRDVGKLSKIRIEHDNAGFGPGWFLDK</span>VIICNLEKPNVKYYCPCNQWLAKDVGDKSISRD LTAYTDPNAAPS<span style="color: #996633;">A
  ELRRSDGQAFQRARVATFTLDDLANLGKLKKLVISHNGHGMASGWFLDKIIVTSLSSNKATVFPCDAWLDRKNGRSKELVARTAAAGAEGMTTFTIRVMT
  03 YVYIVHTFTGNKRGAGTDANVYAVIFGDSGDTGEKRLDNSKNNFEKSR</span>KDTFKLSCSCVGKLERLRIRHDNTGLFAGWYLDKV<span style="color: #996633;">VVEDPQEQQSYTFYCRRWLSKTEDDGEICRDLI VSASGDDGDDSVAPK</span>G
  GDRRGAGTDANVQCTLFGEDGESGPHTLNTSRNDFRRGHTDVFAVSSRKIGTLKRLRIWHDNGGAGPAWFLDAVEVVDEASGQTYRFECNRWLAKDEDDG
  04 YPYHIHVTTSDVKNAGTDAEVYVVMHGEGKKSKELNSGKLVLANSEKKKNTFERAMTDIFHMECAEMLSPLTKLTVGHDNKGLAAGWHLDRa<span style="color: #996633;">IVIDCPTTGIEQTFLCQQWLDRKAGDGLTERELVEA FDMRKTRRP</span>K
  QISRELTCNGDSSWGLKSYKLTIFTGDKRNAGTSANVFCKLVGERGASDNVILENSSKNFQRDRTDIFTVEASDLGSLRHIVLGHDNHGMGAGWYVERFS
  05 QLWFAWIWTSDIRGAGTDANVSMQIYGDKGKSQEIKLGNNTDNFEQATLDKFK<span style="color: #996633;">LEIDQVGVPYKLRIGHDNSNAFPGWHLDKVKLENMNDKEQYLFNCNRWLSRSEEDNEIIRELPAS GPNCPNYP</span>I
  LEVPSEGKLYNVDVKQWFATDMSDGAIERTFRLDNAETLDIAQRLDWKCTIYTSDVANAGTDANVFMQVYGKKGKTDVVPLKNKSDTFERGQTDELRVQL
  06 VIYEVSVHTGNKMGGGTDANVFIKIYGELGDSGYRPLKSSKSHNNKFERNQVDVFHIEAVTLKALKKIKIGHDGNNP<span style="color: #996633;">GAGWFLDKVVIKELNGEASNEFPCNR</span>WLSKSEDDGQIVRELFLK SDTPLLK<span style="color: #996633;">T
  INVGSLRKLRVWHDNKGMASGWHLDRIVLSRDGEEYIFPCAEWLAVSEGDKEIVRELPATGPNVKKPLQLVEYTVRVATGHARFAGTNADVFVMLTGELG
  07 TSYHISVKTGDVRNAGTDANVFIQIFGAKDDTGRVRLKQSLNTSNKFERNRIDKFIIEAAQIGK</span>IEKIIIGHDGKGLGSGWFLDYIELDVPSVGRLYRFSCHQWFDSTEGDRKVERELYPS ECIKSAA<span style="color: #996633;">K
  DSGKRALLRSQTNRNKFERGKEDVFTVAAVDLGKLTSVTVGHNNAGTSAGWFLDKIVVLDPRRGEEEEFPCHRWLAVDADDGQIERELVPKMAEHQAAAT
  08 IPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFK</span>VECEDVGKLRKLRIGHDSAGMGSAWFLDK<span style="color: #996633;">VYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEIS PVGVDGALA</span>E
  TTYIVKIKTGDVRHAGTDANVFVQLFGKTGESTQLKLRNSETYSDAFERNKMDIFKFELLDLGDLSRILVGHDNKGMGAAWFLDYVEVEVPSIRTRWKFP
  09 MTYTIRVITGNKFGCGTNANVFINMYGEEGDSGERQLKKSETHTDKFERNQ<span style="color: #996633;">EDVFKISCLSLGELKKIKIRHDNSGFRPAWFLDKVIIEVGESKYQFMCDRWLAKDEDDGQISRELLPQ SDEQSRAEAIGASKDLQKK</span>VAS
  CSRWFSKSQDDGLTEREIYAEKEAGEPMEEDVSAPYLFRFYTSDVAFAGTDANVSVVLYGDEGKTEELVVNNQSDNFERGKADDFKLACKPVGRPSKIRL
  10 TTYNVSVTTGDIKGAGTDANVHIVLYGEKDDTGLIHLKNSTTHSNKFERNQEDRFVVEAIDIGELKKIK<span style="color: #996633;">IGHDNKGGMAGWFLNKVEIDIPSLGRRLLFPCGRWIDKGKDDGALER ELYPLNEAEETYRP</span>H
  SAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDNGREVVEELALDANKRTYRVKVHTGDQKGAGTDANVYVNLHG
  11 IPYEVTVYTTDKRGASTGANVYVVIYGEENQTEQASLEPDKKRRKQYFKNGAIDKFVLE<span style="color: #996633;">LDDVGEEITKLRIGHDGKGWGAGWHLDKVEICRLLDGGKASKKFTFQCNRWLASDEDDGAIVRELVPS EIVEKSSKDGGQVKTKVTKPTDGLK</span>V
  SLGDSGDRHLKNSLTHTNKFQRKTVDEFDIDAVTLGDINKVKVWHDNAGLGAAWYLEKIEVVDTADDKTYIFPCAQWFAKSMGDGQIARELGVLEEQKPA
  12 KPYTIHVFTGDVDGAGTNANVFLTIFGESGDSGERKLAKSDTHYDKFERNQ<span style="color: #996633;">EDIFHIEAADLGRLFKVKIRHDNTGSLFSPAWFLNRIEIVDDENEETTAFPCERWLAKKKDDGKIDRTLFVK GWEGDTSSVATTRSK</span>ASFRSNSTDLGEMVSASGRRASSRKGPVMAPIDEK<span style="color: #996633;">C
  DFQTKNVGFKYRISVHTSDVKHAGTDANVDIVLYGEKGDTGKIRLAKSETHRDMWERGNCDVFTVSAIELGDLKRVDIMHDGKGVGSGWHLNKVVVDAPQ
  13 VPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVS</span>HNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAA
  AGKTWTFMCDAWLDKATDDGTMAKTLYASADAIEEYSAHVPYEIIIKTSDVRNAGTDANVFIDLYGRDQEERDLTAHHEFKDAVKAHFERNLEDRFNVEL
  14 NAQVTSYTA<span style="color: #996633;">GTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIP</span>LELDDVGTIKKIRIGHDGKGSRTDWYLEK<span style="color: #996633;">ASIQRMDTLDMYMFRANQWFSKKIDDKKLVREI PAETSKEGATTIK</span>K
  PDVGSIYKIRLGHDGKGMSSSWHVASVVVINQRTHERFEFPCDAWLSKDKDDKKLVREFAVGEVKALEGDKVVRRESILSLQEAIYKIHVFTGDIKHAGT
  15 INYVLSTHTSDKRGSGTDANVFVIIFGENGDSGEIALKKSETNWNKFEKGQTDVFLINDRLSLGRLQKLRIWHDNA<span style="color: #996633;">GFGASWHLASVDIVDESTGVKYTFPCDKWLSKSNGDKLILREL PCAETAGNTAASKATKQESKSGK</span>
  DANIYVQIFGDTGDSGEIKLEKSETYRDKFERGHEDIFTHRCLDLGPLRKIKVRSDGKGLMGGDWYLDRVEVHQENDLSEPPVRFVCQDWFKRGKQEGDT
  16 AEYEIAFTTGTEKRAGTNQDVAIVLKGKSEKSREFLIENNEDKKYFSKGKTNKFTYTCKPLGDITKAIVSHRESAIGEEPDSKNSSWYLKVVTVVHKASGTT<span style="color: #996633;">YKFPCNKWIDLDDDEENNSSVTLKC KSADVAASSKAKPV</span>ELKP
  LEREITAQVDAAVAMKEATALEDEAARLQRKATTLSRKSTKGSPLRKGTGTTETNAELEEAQRQANIARRKADEAKERAGLAGADDTQLEYKVTVYTGTD
  17 VKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* </span>
  TQAGTTANVWLQLFGEKDAPLTPAPPSPSKLSRSGSLFGRRRRASSDAQSVSSSLSAGASGPRETSTGRLQLNNAPADLQSGAKTTFTVTGLDVGELVGL
   
  EIGHDDERDKWYLEQVVVEVPKSATHAARRYEFKAGVWLAARADGSTSGSAKGKSKASVRLQPSEIHAGSERILEYTLKVYTASADGAGCTAVPQVQLFG
  <span style="color: #0066CC;">>Monosiga brevicollis (monosiga) Eukaryota|Choanoflagellates XM_001742822 17 PLAT domains [http://www.ncbi.nlm.nih.gov//genomes/geblast.cgi?bact=off&gi=5881 blast] exons colored; PLAT domains numbered
  DKHTTEALPLRAGGDILPASVVETQHRVPDLGALLKVRLMVPRGSSWTVEKVEFGRAGQTPITFVGSDGSAVTLGAERLSFDFLPAAAPASSGGKGKRRG
    MADLPVPTTALQRLQLERSRYSFAAA<span style="color: #996633;">DPPPSFVQRYTSADVLSH</span>RLYAQGLASDVGPGSHSSL<span style="color: #996633;">GMSRRVELPPYNPLNDPALANYFARKFEWNSTRSVGAGSGSRRSASASLTRTRQPVRGASAHGHTKSRTKSSHRK
  STTSSVAVAQQTSYRVYVTTADERGTGTDANVSIILYGAMGDSGEHSLTKSETFDDPFERGNTDVFTLEVPDLGELQRARIWHDGKGMFSSWKLDKIVVV
01 GHASLEIFTSKRSNPVSKSEKYITVVGTKGRSDAIQLAAPGVHFRAGNKDVFQVNLTGIGKPT</span>KVILENTGTKRTDGWCVSKVVLVKKTDKGTRRYRFSGPVWL<span style="color: #996633;">SKHHDEMKLKR        VLHIDDEDIGSG
  VEATQSRYELPCGQWLSKNKGDKQLTRDLAVASKRVNALTGTYKLEVATDSRAGGGCKGPVRIMLLDAEKNQLPLTLEPPGGEFAPGSVEHLVFDNVMLL
  02 NG</span>YRIDCYTGDVANAGTDAVATIQLFGSKGQSPMVELRRSDGQAFQRARVATFTLD<span style="color: #996633;">DLANLGKLKKLVISHNGHGMASGWFLDK</span>IIVTSLSSNKATVFPCDAWLDRKNGRSK<span style="color: #996633;">ELVAR      TAAAGAEGM
  GPLTELRIRRKPSGASSRRGAEDDDEDDNEASGASSQSGSAVSPWHLEHIIVKHLQSGQSFVFKGPSKGLSRSRAKLSVHTEATTEEAVAQATKASVAQY
  03 TTFTIRVMTGDRRGAGT</span>DANVQCTLFGEDGES<span style="color: #996633;">GPHTLNTSRNDFRRGHTDVFAVSSRKIGTLKRLRIWHDNGGAGP</span>AWFLDAVEVVDEASGQTYRFECNRWLAKDEDDGQISRELTCN      GDSSWGL
  EVAVTTGTERGAGTDSNVFVTLFGKNGDSGERALAKSKTFRNMFESGNTDVFDVECQDLGELTKIEVKSDLKGFGAAWQLDKIKVTRTGSQNSWQFKCDQ
  04 KSYKLTIFTGDKRNAGTSANVFCKLVGERGASDNVILENSSKNFQRDRTDIFTVEASDLGSLRHIVLGHDNHGM<span style="color: #996633;">GAGWYVERFSLEVPSEGKLYNVDVKQW</span>FATDMSDGAIERTFRLD      NAETLDIAQR
  WFDKKQGAEHTFSVAS*
  05 LDWKCTIYTSDVANAGTDANVFMQV<span style="color: #996633;">YGKKGKTDVVPLKNKSDTFER</span>GQTDELRVQLINVGSLRKLRVWHDNKGMASGWHLDRIVLSRDGEEY<span style="color: #996633;">IFPCAEWLAVSEGDKEIVRELPAT        GPNVKKPLQL
  06 VEYTVRVATGHARFAGTNADVFVMLTGELGDSGKRALLRSQTNR</span>NKFERGKEDVFTVAAVDLGKLTSVTVGHNNAGTSAGWFLDKIVVLDPRRG<span style="color: #996633;">EEEEFPCHRWLAVDADDGQIERELVPK  MAEHQAAAT
  07 TTYIVKIKTGDVRHAGTDANV</span>FVQLFGKTGESTQLKLRNSETYSDAFERNKMDIFKFELLDLGDLSRILVGHDNKGMGAAWFLDYVEVEVPSIRTRWKFPCSRWFSKSQDDGLTER        EIYAEKEAGEPMEEDVS
  08 APYLFRFYTSDVAFAGTDANV<span style="color: #996633;">SVVLYGDEGKTEELVVNNQSDNFERGKA</span>DDFKLACKPVGRPSKIRLSAHGGGMSADWHLEK<span style="color: #996633;">IEVHELGQARIYTFEHNDWLRKGTKAKPFMVEL        PLRRIETVDDNGREVVEELALDANK
09 RTYRVKVHTGDQKGAGTDAN</span>VYVNLHGSLGDSGDRHLKNSLTHT<span style="color: #996633;">NKFQRKTVDEFDIDAVTLGDINKVKVWHDNA</span>GLGAAWYLEKIEVVDTADDKTYIFPCAQWFAKSMGDGQIAREL      GVLEEQ<span style="color: #996633;">KPADFQTKNVG
10 FKYRISVHTSDVKHAGTDANVDIVLYGEKGDTGKIRLAKSETHRDMW</span>ERGNCDVFTVSAIELGDLKRVDIMHDGKGVGSGWHLNKVVVDAPQAGKTWTFMCDAWLDKATDDGTMAK        TLYASADAIEEYSAH
11 VPYEIIIKTSDVRNAGTDANVFIDLYGRDQEERDLTAHHEFKDAVKAHFERNLEDRFNVELPDVGSIYKIRLGHDGKGMSSSWHVASVVVINQRTHERFEFPCDAWLSKDKDDKKLVREFAVG EVKALEGDKVVRRESILSLQE
12 AIYKIHVFTGDIKHAGTDANIYVQIFGDTGDSGEIKLEKSETYRDKFERGHEDIFTHRCLDLGPLRKIKVRSDGKGLMGGDWYLDRVEVHQENDLSEPPVRFVCQDWFKRGKQEGDTLEREITAQ
    VDAAVAMKEATALEDEAARLQRKATTLSRKSTKGSPLRKGTGTTETNAELEEAQRQANIARRKADEAKERAGLAGADDTQ
13 LEYKVTVYTGTDTQAGTTANVWLQLFGEKDAPLTPAPPSPSKLSRSGSLFGRRRRASSDAQSVSSSLSAGASGPRETSTGRLQLNNAPADLQSGAKTTFTVTGLDVGELVGLEIGHDDERDKWYLEQVVVEVPKSATHAARRYEFKAGVWLAARADGSTSGSAK GKSKASVRLQPSEIHAGSERI
14 LEYTLKVYTASADGAGCTAVPQVQLFGDKHTTEALPLRAGGDILPASVVETQHRVPDLGALLKVRLMVPRGSSWTVEKVEFGRAGQTPITFVGSDGSAVTLGAERLS FDFLPAAAPASSGGKGKRRGSTTSSVAVAQQ
15 TSYRVYVTTADERGTGTDANVSIILYGAMGDSGEHSLTKSETFDDPFERGNTDVFTLEVPDLGELQRARIWHDGKGMFSSWKLDKIVVVVEATQSRYELPCGQWLSKNKGDKQLTRDLAVASKR VNALT
16 GTYKLEVATDSRAGGGCKGPVRIMLLDAEKNQLPLTLEPPGGEFAPGSVEHLVFDNVMLLGPLTELRIRRKPSGASSRRGAEDDDEDDNEASGASSQSGSAVSPWHLEHIIVKHLQSGQSFVFKGPSKGLSRSRAKLSVHTEA TTEEAVAQATKASV
17 AQYEVAVTTGTERGAGTDSN<span style="color: #996633;">VFVTLFGKNGDSGERALAKSKTFRNMFESGNTDVFD</span>VECQDLGELTKIEVK<span style="color: #996633;">SDLKGFGAAWQLDKIKVTRTGSQNSWQFKCDQWFDKKQGAEHTFSVA S*</span></span>


  >LOXHD1_homSap_full dna: each line is an exon
  >LOXHD1_homSap_full dna: each line is an exon
Line 346: Line 451:


=== Reference PLAT domain sets ===
=== Reference PLAT domain sets ===
 
  <span style="color: #990099;">>LOXHD1_homSap_PLAT:01
  <span style="color: #990099;">
>LOXHD1_homSap_LH2:01 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  RVYEVVTATGDVRGAGTDANVFITLFGENGLSPKLQLTSKSKSAFEKGNVDVFRVRTNNVGLIYKVRIEHDNTGLNASWYLDHVIVTDMKRPHLRYYFNCNNWLSKVEGDRQWCRD
  RVYEVVTATGDVRGAGTDANVFITLFGENGLSPKLQLTSKSKSAFEKGNVDVFRVRTNNVGLIYKVRIEHDNTGLNASWYLDHVIVTDMKRPHLRYYFNCNNWLSKVEGDRQWCRD
   
   
  >LOXHD1_homSap_LH2:02 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:02
  NKYEVKVYTGDVIGAGTDADVFINIFGEYGDTGERRLENEKDNFEKGAEDRFILDAPDLGQLMKINVGHNNKGGSAGWFLSQIVIEDIGNKRKYDFPLNRWLALDEDDGKIQRDILVGG
  NKYEVKVYTGDVIGAGTDADVFINIFGEYGDTGERRLENEKDNFEKGAEDRFILDAPDLGQLMKINVGHNNKGGSAGWFLSQIVIEDIGNKRKYDFPLNRWLALDEDDGKIQRDILVGG
   
   
  >LOXHD1_homSap_LH2:03 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:03
  ITYIVTVFTGDVRGAGTKSKIYLVMYGARGNKNSGKIFLEGGVFDRGRTDIFHIELAVLLSPLSRVSVGHGNVGVNRGWFCEKVVILCPFTGIQQTFPCSNWLDEKKADGLIER
  ITYIVTVFTGDVRGAGTKSKIYLVMYGARGNKNSGKIFLEGGVFDRGRTDIFHIELAVLLSPLSRVSVGHGNVGVNRGWFCEKVVILCPFTGIQQTFPCSNWLDEKKADGLIER
   
   
  >LOXHD1_homSap_LH2:04 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:04
  FPWSLWVWTTDLKKAGTNSPIFIQIYGQKGRTDEILLNPNNKWFKPGIIEKFRIELPDLGRFYKIRVWHDKRSSGSGWHLERMTLMNTLNKDKYNFNCNRWLDANEDDNEIVREM
  FPWSLWVWTTDLKKAGTNSPIFIQIYGQKGRTDEILLNPNNKWFKPGIIEKFRIELPDLGRFYKIRVWHDKRSSGSGWHLERMTLMNTLNKDKYNFNCNRWLDANEDDNEIVREM
   
   
  >LOXHD1_homSap_LH2:05 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:05
  ARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPS
  ARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPS
   
   
  >LOXHD1_homSap_LH2:06 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:06
  FRYHISLKTGDVSGASTDSRVYIKLYGDKSDTIKQVLLVSDNNLKDYFERGRVDEFTLETLNIGNINRLVIGHDSTGMHASWFLGSVQIRVPRQGKQYTFPANRWLDKNQADGRLEV
  FRYHISLKTGDVSGASTDSRVYIKLYGDKSDTIKQVLLVSDNNLKDYFERGRVDEFTLETLNIGNINRLVIGHDSTGMHASWFLGSVQIRVPRQGKQYTFPANRWLDKNQADGRLEV
   
   
  >LOXHD1_homSap_LH2:07 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:07
  VHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQLEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLR
  VHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQLEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLR
   
   
  >LOXHD1_homSap_LH2:08 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:08
  NTYEVQVVTGNVPKAGTDANVYLTIYGEEYGDTGERPLKKSDKSNKFEQGQTDTFTIYAIDLGALTKIRIRHDNTGNRAGWFLDRIDITDMNNEITYYFPCQRWLAVEEDDGQLSRELLPV
  NTYEVQVVTGNVPKAGTDANVYLTIYGEEYGDTGERPLKKSDKSNKFEQGQTDTFTIYAIDLGALTKIRIRHDNTGNRAGWFLDRIDITDMNNEITYYFPCQRWLAVEEDDGQLSRELLPV
   
   
  >LOXHD1_homSap_LH2:09 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:09
  TTFSVTIKTGVKKNAGTDANVFITLFGTQDDTGMTLLKSSKTNSDKFERDSIEIFTVETLDLGDLWKVRLGHDNTGKAPGWFVDWVEVDAPSLGKCMTFPCGRWLAKNEDDGSIIRDLFHA
  TTFSVTIKTGVKKNAGTDANVFITLFGTQDDTGMTLLKSSKTNSDKFERDSIEIFTVETLDLGDLWKVRLGHDNTGKAPGWFVDWVEVDAPSLGKCMTFPCGRWLAKNEDDGSIIRDLFHA
   
   
  >LOXHD1_homSap_LH2:10 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:10
  VPYEITLYTSDVFAAGTDANIFIIIYGCDAVCTQQKYLCTNKREQKQFFERKSASRFIVELEDVGEIIEKIRIGHNNTGMNPGWHCSHVDIRRLLPDKDGAETLTFPCDRWLATSEDDKKTIRELVP
  VPYEITLYTSDVFAAGTDANIFIIIYGCDAVCTQQKYLCTNKREQKQFFERKSASRFIVELEDVGEIIEKIRIGHNNTGMNPGWHCSHVDIRRLLPDKDGAETLTFPCDRWLATSEDDKKTIRELVP
   
   
  >LOXHD1_homSap_LH2:11 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:11
  VLYSVQIFTGNIPGAGTDAKVYITIYGDLGDTGERYLGKSENRTNKFERGTADTFIIEAADLGVIYKIKLRHDNSKWCADWYVEKVEIWNDTNEDEFLFLCGRWLSLKKEDGRLERLFYEK
  VLYSVQIFTGNIPGAGTDAKVYITIYGDLGDTGERYLGKSENRTNKFERGTADTFIIEAADLGVIYKIKLRHDNSKWCADWYVEKVEIWNDTNEDEFLFLCGRWLSLKKEDGRLERLFYEK
   
   
  >LOXHD1_homSap_LH2:12 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:12
  IPYYVSVTTGKHKDAATDSRAFIFLIGEDDERSKRIWLDYPRGKRGFSRGSVEEFYVAGLDVGIIKKIELGHDGASPESCWLVEELCLAVPTQGTKYMLNCNCWLAKDRGDGITSRVFD
  IPYYVSVTTGKHKDAATDSRAFIFLIGEDDERSKRIWLDYPRGKRGFSRGSVEEFYVAGLDVGIIKKIELGHDGASPESCWLVEELCLAVPTQGTKYMLNCNCWLAKDRGDGITSRVFD
   
   
  >LOXHD1_homSap_LH2:13 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:13
  VLYEMTVWTGDVVGGGTDSNIFMTLYGINGSTEEMQLDKKKARFEREQNDTFIMEILDIAPFTKMRIRIDGLGSRPEWFLERILLKNMNTGDLTMFYYGDWLSQRKGKKTLVC
  VLYEMTVWTGDVVGGGTDSNIFMTLYGINGSTEEMQLDKKKARFEREQNDTFIMEILDIAPFTKMRIRIDGLGSRPEWFLERILLKNMNTGDLTMFYYGDWLSQRKGKKTLVC
   
   
  >LOXHD1_homSap_LH2:14 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:14
  TSYTVAVKTSDILGAGTDANVFIIIFGENGDSGTLALKQSANWNKFERNNTDTFNFPDMLSLGHLCKLRVWHDNKGIFPGWHLSYVDVKDNSRDETFHFQCDCWLSKSEGDGQTVRDFAC
  TSYTVAVKTSDILGAGTDANVFIIIFGENGDSGTLALKQSANWNKFERNNTDTFNFPDMLSLGHLCKLRVWHDNKGIFPGWHLSYVDVKDNSRDETFHFQCDCWLSKSEGDGQTVRDFAC
   
   
  >LOXHD1_homSap_LH2:15 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:15
  TTYEIVIETGNGGETRENVWLILEGRKNRSKEFLMENSSRQRAFRKGTTDTFEFDSIYLGDIASLCVGHLAREDRFIPKRELAWHVKTITITEMEYGNVYFFNCDCLIPLKRKRKYFKVF
  TTYEIVIETGNGGETRENVWLILEGRKNRSKEFLMENSSRQRAFRKGTTDTFEFDSIYLGDIASLCVGHLAREDRFIPKRELAWHVKTITITEMEYGNVYFFNCDCLIPLKRKRKYFKVF
   
   
  >LOXHD1_homSap_LH2:16 chr18: 42343528 Lipoxygenase homology no other domains  pdb:3DY5
  >LOXHD1_homSap_PLAT:16
  VKYEVIVTTGYEPGAGTDANVFVTIFGANGDTGKRELKQKMRNLFERGSTDRFFLETLELGELRKVRLEHDSSGYCSGWLVEKVEVTNTSTGVATIFNCGRWLDKKRGDGLTWRDLFPS
  VKYEVIVTTGYEPGAGTDANVFVTIFGANGDTGKRELKQKMRNLFERGSTDRFFLETLELGELRKVRLEHDSSGYCSGWLVEKVEVTNTSTGVATIFNCGRWLDKKRGDGLTWRDLFPS
</span>
</span><font color="green">
<span style="color: #996633;">
  >PKD1L1_homSap_PLAT chr7: 47780815 polycystin-1L1 GPS-TM-LH2-TM pdb:3CWZ
  >PKD1L2_homSap_LH2:01 chr16: 79691985 polycystin 1-like 2 signal...GPS-TM-LH2-TM  pdb:3CWZ
QLYAVVIDTGFRAPARLTSKVYIVLCGDNGLSETKELSCPEKPLFERNSRHTFILSAPAQLGLLRKIRLWHDSRGPSPGWFISHVMVKELHTGQGWFFPAQCWLSAGRHDGRVERELTC
>PKD1_homSap_PLAT chr16: 2078712 polycystin 1 GPS-TM-LH2-TM pdb:3CWZ
FKYEILVKTGWGRGSGTTAHVGIMLYGVDSRSGHRHLDGDRAFHRNSLDIFRIATPHSLGSVWKIRVWHDNKGLSPAWFLQHVIVRDLQTARSAFFLVNDWLSVETEANGGLVEK
>PKD1L2_homSap_PLAT chr16: 79691985 polycystin 1-like 2 signal...GPS-TM-LH2-TM pdb:3CWZ  
  YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSWYVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA
  YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSWYVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA
   
   
  >PKDREJ_homSap_LH2:01 chr22: 45030224 receptor for egg jelly-like signal...GPS-TM-LH2-TM  pdb:3CWZ
  >PKD1L3_homSap chr16:70,556,160 GPS-TM-LH2-TM polycystic kidney disease 1-like 3
FHYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHHLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSWYVSQVIVCDMAVKRKWHFLCNCWLAVDLGDCELDRVFIPV
>PKDREJ_homSap_PLAT chr22: 45030224 receptor for egg jelly-like signal...GPS-TM-LH2-TM pdb:3CWZ
  CYLVTIFTGSRWGSGTRANVFVQLRGTVSTSDVHCLSHPHFTTLYRGSINTFLLTTKSDLGDIHSIRVWHNNEGRSPSWYLSRIKVENLFSRHIWLFICQKWLSVDTTLDRTFHVT
  CYLVTIFTGSRWGSGTRANVFVQLRGTVSTSDVHCLSHPHFTTLYRGSINTFLLTTKSDLGDIHSIRVWHNNEGRSPSWYLSRIKVENLFSRHIWLFICQKWLSVDTTLDRTFHVT
   
   
  >PKD1L1_homSap_LH2:01 chr7: 47780815 polycystin-1L1 GPS-TM-LH2-TM  pdb:3CWZ
  >DENND5A_homSap_PLAT chr11: 9116949 RAB6 interacting 1 RUN-LH2-RUN pdb:3CWZ
  QLYAVVIDTGFRAPARLTSKVYIVLCGDNGLSETKELSCPEKPLFERNSRHTFILSAPAQLGLLRKIRLWHDSRGPSPGWFISHVMVKELHTGQGWFFPAQCWLSAGRHDGRVERELTC
LIHILIVPSKKLGGSMFTANPWICISGELGETQIMQIPRNVLEMTFECQNLGKLTTVQIGHDNSGLYAKWLVEYVMVRNEITGHTYKFPCGRWLGKGMDDGSLER
>DENND5B_homSap_PLAT chr12: 31426424 RAB6 interacting 2 RUN-LH2-RUN pdb:3CWZ
PYRSVIIPIKKLSNAIITSNPWICVSGELGDTGVMQIPKNLLEMTFECQNLGKLTTVQIGHDNSGLLAKWLVDCVMVRNEITGHTYRFPCGRWLGKGIDDGSLER
>ALOX5_homSap_PLAT chr10: 45189635 arachidonate 5-lipoxygenase NH2-LH2-lipox pdb:2P0M
  PSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDG
   
   
  >PKD1_homSap_LH2:01 chr16: 2078712 polycystin 1 GPS-TM-LH2-TM  pdb:3CWZ
  >ALOX15_homSap_PLAT chr17: 4480963 arachidonate 15-lipoxygenase NH2-LH2-lipox pdb:2P0M
  FKYEILVKTGWGRGSGTTAHVGIMLYGVDSRSGHRHLDGDRAFHRNSLDIFRIATPHSLGSVWKIRVWHDNKGLSPAWFLQHVIVRDLQTARSAFFLVNDWLSVETEANGGLVEK
  GLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPLLFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEG
   
   
  >DENND5B_homSap_LH2:01 chr12: 31426424 DENN/MADD domain 5B RUN-LH2-RUN  pdb:3CWZ
  >ALOX15_oryCun Oryctolagus cuniculus (rabbit) arachidonate 15-lipoxygenase 15S-LOX1 PDB:P0M
  RSVIIPIKKLSNAIITSNPWICVSGELGDTGVMQIPKNLLEMTFECQNLGKLTTVQIGHDNSGLLAKWLVDCVMVRNEITGHTYRFPCGRWLGKGIDDGSLER
  GVYRVCVSTGASIYAGSKNKVELWLVGQHGEVELGSCLRPTRNKEEEFKVNVSKYLGSLLFVRLRKKHFLKEDAWFCNWISVQALGAAEDKYWFPCYRWVVGDGVQSLPVG
   
   
  >DENND5A_homSap_LH2:01 chr11: 9116949 RAB6 interacting protein 1 RUN-LH2-RUN  pdb:3CWZ
  >ALOX12_homSap_PLAT chr17: 6840108 arachidonate 12-lipoxygenase NH2-LH2-lipox pdb:2P0M
  HILIVPSKKLGGSMFTANPWICISGELGETQIMQIPRNVLEMTFECQNLGKLTTVQIGHDNSGLYAKWLVEYVMVRNEITGHTYKFPCGRWLGKGMDDGSLER
  GRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLLQFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEG
   
   
  >ALOX5_homSap_LH2:01 chr10: 45189635 arachidonate 5-lipoxygenase NH2-LH2-lipox  pdb:2P0M
  >ALOX15B_homSap_PLAT chr17 7,888,129 arachidonate 15-lipoxygenase NH2-LH2-lipox pdb:2P0M
  PSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDG
AEFRVRVSTGEAFGAGTWDKVSVSIVGTRGESPPLPLDNLGKEFTAGAEEDFQVTLPEDVGRVLLLRVHKAPPVLPLLGPLAPDAWFCRWFQLTPPRGGHLLFPCYQWLEGAGTLVLQEG
>ALOX12B_homSap_PLAT chr17: 7916679 arachidonate 12R-lipoxygenase NH2-LH2-lipox pdb:2P0M
  ATYKVRVATGTDLLSGTRDSISLTIVGTQGESHKQLLNHFGRDFATGAVGQYTVQCPQDLGELIIIRLHKERYAFFPKDPWYCNYVQICAPNGRIYHFPAYQWMDGYETLALREA
   
   
  >ALOXE3_homSap_LH2:01 chr17: 7939943 arachidonate lipoxygenase 3 NH2-LH2-lipox  pdb:2P0M
  >ALOXE3_homSap_PLAT chr17: 7939943 arachidonate lipoxygenase 3 NH2-LH2-lipox pdb:2P0M
  AVYRLCVTTGPYLRAGTLDNISVTLVGTCGESPKQRLDRMGRDFAPGSVQKYKVRCTAELGELLLLRVHKERYAFFRKDSWYCSRICVTEPDGSVSHFPCYQWIEGYCTVELRPG
  AVYRLCVTTGPYLRAGTLDNISVTLVGTCGESPKQRLDRMGRDFAPGSVQKYKVRCTAELGELLLLRVHKERYAFFRKDSWYCSRICVTEPDGSVSHFPCYQWIEGYCTVELRPG
   
   
  >ALOX15_homSap_LH2:01 chr17: 4480963 arachidonate 15-lipoxygenase NH2-LH2-lipox  pdb:2P0M
  >LIPC_homSap LIP-PLAT chr15:56511467 lipase C
  GLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPLLFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEG
YHYQLKIQFINQTETPIQTTFTMSLLGTKEKMQKIPITLGKGIASNKTYSFLITLDVDIGELIMIKFKWENSAVWANVWDTVQTIIPWSTGPRHSGLVLKTIRVKAGETQQRMTFCSEN
>LIPG_homSap LIP-PLAT chr18:45342425 endothelial lipase
YHYQMKIHVFSYKNMGEIEPTFYVTLYGTNADSQTLPLEIVERIEQNATNTFLVYTEEDLGDLLKIQLTWEGASQSWYNLWKEFRSYLSQPRNPGRELNIRRIRVKSGETQRKLTFCTEDPEN
>LPL_homSap LIP-PLAT chr8:19840862 lipoprotein lipase
FHYQVKIHFSGTESETHTNQAFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIQKIRVKAGETQKKVIFCSREKVSHLQKGKAPAVFVKC
>PNLIP_homSap LIP-PLAT chr10:118295418 pancreatic lipase
WRYKVSVTLSGKKVTGHILVSLFGNKGNSKQYEIFKGTLKPDSTHSNEFDSDVDVGDLQMVKFIWYNNVINPTLPRVGASKIIVETNVGKQFNFCSPETVREEVLLTLTPC
>PNLIPRP1_homSap LIP-PLAT chr10:118340480 pancreatic lipase-related 1
WRYGVSITLSGRTATGQIKVALFGNKGNTHQYSIFRGILKPGSTHSYEFDAKLDVGTIEKVKFLWNNNVINPTLPKVGATKITVQKGEEKTVYNFCSEDTVREDTLLTLTPC
>PNLIPRP2_homSap LIP-PLAT chr10:118370455 pancreatic lipase-related 2
WRYKVSVTLSGKEKVNGYIRIALYGSNENSKQYEIFKGSLKPDASHTCAIDVDFNVGKIQKVKFLWNKRGINLSEPKLGASQITVQSGEDGTEYNFCSSDTVEENVLQSLYPC
>PNLIPRP3_homSap LIP-PLAT chr10:118177414 pancreatic lipase-related protein 3  chr16:70520943
WRHKLSVKLSGSEVTQGTVFLRVGGAVRKTGEFAIVSGKLEPGMTYTKLIDADVNVGNITSVQFIWKKHLFEDSQNKLGAEMVINTSGKYGYKSTFCSQDIMGPNILQNLKPC</font>
>PLAT_cloPer Clostridium perfringens phospholipase toxin DQ183948
KELVAYISTSGEKDAGTDDYMYFGIKTKDGKTQEWEMDNPGNDFMTGSKDTYTFKLKDENLKIDDIQNMWIRKRKYTAFPDAYKPENIKVIANGKVVVDKDINEWISGNSTYNIK
>ALOX_8R_pleHom Plexaura homomalla (coral) 8R-Lipoxygenase LOX-8R beta calcium membrane
AIYNVEVETGDREHAGTDATITIRITGAKGRTDYLKLDKWFHNDFEAGSKEQYTVQGFDVGDIQLIELHSDGGGYWSGDPDWFVNRVIIISSTQDRVYSFPCFRWVIKDMVLFPGEA
<font color="purple">>LOXHD1_galGal_PLAT:01
KVYEVVTVTGDVRGAGTDANVFVTLFGEFGITPKTHLTSKSSTAFERSKTDVFRVKTNNVGQIKKIRIEHDNTGLNAGWFLDRVIVTDMNRPhLRFYFPCNNWLSKEDGDGLYVRDLI
>LOXHD1_galGal_PLAT:02
NKYVVRVFTGEVSGSGTDADVFINIFGEKGDTGVRKLDNDKDNFEKGAEDKFTLDAPNLGRLRKINIGHNNKGGSAGWFLAKVIIEDIGNKCVYQFPVGRWFALDEDDGKIQRDIL
>LOXHD1_galGal_PLAT:03
IVYNVAVVTGDIRGAGTNSKIHVILHGSKglKNSGTIFLEGGEFERARTDLFNVEIASLLSPLSRVTIGHDNCGVSSGWYCEKVVVYCPFTGIEQTFPCGKWLDEDEGDGLIERELY
>LOXHD1_galGal_PLAT:04
NPWSLWIWTSDIKNAGTDATIFFQIYGDKGKSDEMKLDNNSDNFEAGQTDKFMIELPDLGTFYKLRIWHEKRNPFAGWHLDKVTLLKTLTKDKYSFNCGRWLDINEDDNEIVRELP
>LOXHD1_galGal_PLAT:05
IKYRVTVCTGMVSGSGTDANVFVCLIGDQGDTGDRVLYKCinNVNKFEKGNADEFFVEAVTLKQVRRVRIGHDGKGGSSGWYLAKVIVREEGQPesEAVEFPCYRWLDKNEDDGQIVRELV
>LOXHD1_galGal_PLAT:06
VSYHISVKTGDIPGASSDSKVFIKLYGEKADTSKETLLVSdndLGNYFERGRVDEFTIDTMDIGKINRILIGHDNVGLRSGWFLASVQITVPVQGRQYMFPCNRWLDKDEADGRVEVEVY
>LOXHD1_galGal_PLAT:07
INYEVSVVTGDVRAAGTNAKVFMQIYGETGKTELIILENRSNNFERGATDIFEVEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKmdetdkkkkkkkkkseeeeeeeetkveevmDVYTFVAHRWLAKDEGDKELVVELV
>LOXHD1_galGal_PLAT:08
NTYEVHVLTGSVWGSGTDANVFLSIYGIErGDTGERQLKRSnNLNKFEKGQVDVFTIKAIDLGELKKLRIRHDNSGSSPSWFLERVEIVDLKESTTYYFPCQRWLAVEEDDGQIVRELV
>LOXHD1_galGal_PLAT:09
TTYIVKVKTGDKKNAGTDANVFITLYGSKDDTGIVSLKASklNKNKFERGKIDEFTVESVDIGDLKKIKIGHDNAGNSNGWFLEWVEIDAPSLGQCLKFPCGRWLDKSEDDGAIERFIF
>LOXHD1_galGal_PLAT:10
VPYEITVYTSDIFGAGTDADVFIVLYGSDgicTQQKSLCLNKReQRMYFERNSVNQFIVELEDVGDIIEKIRIGHNGGGLNSGWHLDRVAIRRLLPNgkgsETITFPCERWLAKSEDDGEIIRELV
>LOXHD1_galGal_PLAT:12
IPYHITVTTGTEYDSSTDSRVFIIIMGPQkVRTERLWLDLPeGKDEFADGSVEKFSVWGLDVGEIKKVEVGHDGATPESCWLMEELTIVVPTKGVMYNFVCKCWLARDKGDGLTSRILN
>LOXHD1_galGal_PLAT:13
ILYEVTVVTGDIESGGTDAGIFMTVFGSNGNTEEMQLDKNGDRFERGQEDSFIMEIADIAPLRKMRIRTDAKGTRPDWFLERIVMRNLTNQEVATFTYGDWLSKVKNAKGSLVCEM
>LOXHD1_galGal_PLAT:14
  TTYTIQVKTSDIGGAGTDANVSLILFGENGDSGTLALKESnKSNKFERNQMDEFNFPNMLSLGDLCKVRIWHDNKAY
   
   
  >ALOX12B_homSap_LH2:01 chr17: 7916679 arachidonate 12R-lipoxygenase NH2-LH2-lipox  pdb:2P0M
  >LOXHD1_galGal_PLAT:15
  ATYKVRVATGTDLLSGTRDSISLTIVGTQGESHKQLLNHFGRDFATGAVGQYTVQCPQDLGELIIIRLHKERYAFFPKDPWYCNYVQICAPNGRIYHFPAYQWMDGYETLALREA
  KAYEIVTVTSNREDAETKENIWIILEGKLGRSKEFLMENSskKRRFERRGSTDTFQFSSKNLGDIAAICVGHCPKDgkkssakADVYWHVKEIIITEMELCNKYFFRCNGKIPLRYKRRDYKVFEC
   
   
  >ALOX12_homSap_LH2:01 chr17: 6840108 arachidonate 12-lipoxygenase NH2-LH2-lipox  pdb:2P0M
  >LOXHD1_galGal_PLAT:16
  GRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLLQFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEG
  VKYETIVVTGFEKGAGTDANVFITIFGLNGDSGKRALKQKFRNLFERGKTNRFYLETLD
</span>
MGELKKVRIEHDNSGLAPGWLVERVEITNSATGVTTIFPCGKWLDENRGDGLTWRELF</font>
  <span style="color: #0066CC;">
  <span style="color: #0066CC;">
  >LOXHD1_schMan_PLAT:01 Schistosoma mansoni (flatworm) Bilatera; Platyhelminthes; Trematoda XP_002576380 from contig NS_000200
  >LOXHD1_schMan_PLAT:01 Schistosoma mansoni (flatworm) Bilatera; Platyhelminthes; Trematoda XP_002576380 from contig NS_000200
Line 471: Line 654:
   
   
  >LOXHD1_schMan_PLAT:14
  >LOXHD1_schMan_PLAT:14
  IFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNSIDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCS
  TCLDIFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNSIDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCS
   
   
  >LOXHD1_schMan_PLAT:15
  >LOXHD1_schMan_PLAT:15
Line 477: Line 660:
   
   
  >LOXHD1_schMan_PLAT:16
  >LOXHD1_schMan_PLAT:16
  VMYKVSIYTGTKGCANTDANIFITMFSTTPGLNSGRIALKRENNNLFDRKQLDEFYVESIDLESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVS
  VMYKVSIYTGTKGCANTDANIFITMFSTTPGLNSGRIALKRENNNLFDRKQLDEFYVESIDLESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVS</span>
  </span>
  <font color="red">
>LOXHD1_triAdh_PLAT:01
VAYQFGVKTGDKKGSDTDAVYIQVIGTKDKIPKKRLFKKQETEKTERGNLFKFDKSTVEKFAVQHRDIGDPVKLIVEHDGNEKRHGWFLEEITLTNIQSKKSWLFPCHKWLSKYEGDRKLCYE LKPLAKAGK
>LOXHD1_triAdh_PLAT:02
AVYEVSVLTGDKRGAGTDANVSVTLFGKHTSSPKIQLLKSSKHKNPFERNNTDEFKIRTRDVGKLSKIRIEHDNAGFGPGWFLDKVIICNLEKPNVKYYCPCNQWLAKDVGDKSISRD LTAYTDPNAAPSA
>LOXHD1_triAdh_PLAT:03
YVYIVHTFTGNKRGAGTDANVYAVIFGDSGDTGEKRLDNSKNNFEKSRKDTFKLSCSCVGKLERLRIRHDNTGLFAGWYLDKVVVEDPQEQQSYTFYCRRWLSKTEDDGEICRDLI VSASGDDGDDSVAPKG
>LOXHD1_triAdh_PLAT:04
YPYHIHVTTSDVKNAGTDAEVYVVMHGEGKKSKELNSGKLVLANSEKKKNTFERAMTDIFHMECAEMLSPLTKLTVGHDNKGLAAGWHLDRaIVIDCPTTGIEQTFLCQQWLDRKAGDGLTERELVEA FDMRKTRRPK
>LOXHD1_triAdh_PLAT:05
QLWFAWIWTSDIRGAGTDANVSMQIYGDKGKSQEIKLGNNTDNFEQATLDKFKLEIDQVGVPYKLRIGHDNSNAFPGWHLDKVKLENMNDKEQYLFNCNRWLSRSEEDNEIIRELPAS GPNCPNYPI
>LOXHD1_triAdh_PLAT:06
VIYEVSVHTGNKMGGGTDANVFIKIYGELGDSGYRPLKSSKSHNNKFERNQVDVFHIEAVTLKALKKIKIGHDGNNPGAGWFLDKVVIKELNGEASNEFPCNRWLSKSEDDGQIVRELFLK SDTPLLKT
>LOXHD1_triAdh_PLAT:07
TSYHISVKTGDVRNAGTDANVFIQIFGAKDDTGRVRLKQSLNTSNKFERNRIDKFIIEAAQIGKIEKIIIGHDGKGLGSGWFLDYIELDVPSVGRLYRFSCHQWFDSTEGDRKVERELYPS ECIKSAAK
>LOXHD1_triAdh_PLAT:08
IPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFKVECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEIS PVGVDGALAE
>LOXHD1_triAdh_PLAT:09
MTYTIRVITGNKFGCGTNANVFINMYGEEGDSGERQLKKSETHTDKFERNQEDVFKISCLSLGELKKIKIRHDNSGFRPAWFLDKVIIEVGESKYQFMCDRWLAKDEDDGQISRELLPQ SDEQSRAEAIGASKDLQKKVAS
>LOXHD1_triAdh_PLAT:10
TTYNVSVTTGDIKGAGTDANVHIVLYGEKDDTGLIHLKNSTTHSNKFERNQEDRFVVEAIDIGELKKIKIGHDNKGGMAGWFLNKVEIDIPSLGRRLLFPCGRWIDKGKDDGALER ELYPLNEAEETYRPH
>LOXHD1_triAdh_PLAT:11
IPYEVTVYTTDKRGASTGANVYVVIYGEENQTEQASLEPDKKRRKQYFKNGAIDKFVLELDDVGEEITKLRIGHDGKGWGAGWHLDKVEICRLLDGGKASKKFTFQCNRWLASDEDDGAIVRELVPS EIVEKSSKDGGQVKTKVTKPTDGLKV
>LOXHD1_triAdh_PLAT:12
KPYTIHVFTGDVDGAGTNANVFLTIFGESGDSGERKLAKSDTHYDKFERNQEDIFHIEAADLGRLFKVKIRHDNTGSLFSPAWFLNRIEIVDDENEETTAFPCERWLAKKKDDGKIDRTLFVK
>LOXHD1_triAdh_PLAT:13
VPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVSHNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAA
>LOXHD1_triAdh_PLAT:14
KPYELTIHTGDVQNAGTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIPLELDDVGTIKKIRIGHDGKGSRTDWYLEKASIQRMDTLDMYMFRANQWFSKKIDDKKLVREI PAETSKEGATTIKK
>LOXHD1_triAdh_PLAT:15
INYVLSTHTSDKRGSGTDANVFVIIFGENGDSGEIALKKSETNWNKFEKGQTDVFLINDRLSLGRLQKLRIWHDNAGFGASWHLASVDIVDESTGVKYTFPCDKWLSKSNGDKLILREL PCAETAGNTAASKATKQESKSGK
>LOXHD1_triAdh_PLAT:16
AEYEIAFTTGTEKRAGTNQDVAIVLKGKSEKSREFLIENNEDKKYFSKGKTNKFTYTCKPLGDITKAIVSHRESAIGEEPDSKNSSWYLKVVTVVHKASGTTYKFPCNKWIDLDDDEENNSSVTLKC KSADVAASSKAKPVELKP
>LOXHD1_triAdh_PLAT:17
VKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* </font>
<span style="color: #00CC66;">
>LOXHD1_monBre_PLAT:01 Monosiga brevicollis (monosiga)
GHASLEIFTSKRSNPVSKSEKYITVVGTKGRSDAIQLAAPGVHFRAGNKDVFQVNLTGIGKPTKVILENTGTKRTDGWCVSKVVLVKKTDKGTRRYRFSGPVWLSKHHDEMKLKR
>LOXHD1_monBre_PLAT:02 Monosiga brevicollis (monosiga)
NGYRIDCYTGDVANAGTDAVATIQLFGSKGQSPMVELRRSDGQAFQRARVATFTLDDLANLGKLKKLVISHNGHGMASGWFLDKIIVTSLSSNKATVFPCDAWLDRKNGRSKELVAR
>LOXHD1_monBre_PLAT:03 Monosiga brevicollis (monosiga)
TTFTIRVMTGDRRGAGTDANVQCTLFGEDGESGPHTLNTSRNDFRRGHTDVFAVSSRKIGTLKRLRIWHDNGGAGPAWFLDAVEVVDEASGQTYRFECNRWLAKDEDDGQISRELTCN
>LOXHD1_monBre_PLAT:04 Monosiga brevicollis (monosiga)
KSYKLTIFTGDKRNAGTSANVFCKLVGERGASDNVILENSSKNFQRDRTDIFTVEASDLGSLRHIVLGHDNHGMGAGWYVERFSLEVPSEGKLYNVDVKQWFATDMSDGAIERTFRLD
>LOXHD1_monBre_PLAT:05 Monosiga brevicollis (monosiga)
LDWKCTIYTSDVANAGTDANVFMQVYGKKGKTDVVPLKNKSDTFERGQTDELRVQLINVGSLRKLRVWHDNKGMASGWHLDRIVLSRDGEEYIFPCAEWLAVSEGDKEIVRELPAT
>LOXHD1_monBre_PLAT:06 Monosiga brevicollis (monosiga)
VEYTVRVATGHARFAGTNADVFVMLTGELGDSGKRALLRSQTNRNKFERGKEDVFTVAAVDLGKLTSVTVGHNNAGTSAGWFLDKIVVLDPRRGEEEEFPCHRWLAVDADDGQIERELVPK
>LOXHD1_monBre_PLAT:07 Monosiga brevicollis (monosiga)
TTYIVKIKTGDVRHAGTDANVFVQLFGKTGESTQLKLRNSETYSDAFERNKMDIFKFELLDLGDLSRILVGHDNKGMGAAWFLDYVEVEVPSIRTRWKFPCSRWFSKSQDDGLTER
>LOXHD1_monBre_PLAT:08 Monosiga brevicollis (monosiga)
APYLFRFYTSDVAFAGTDANVSVVLYGDEGKTEELVVNNQSDNFERGKADDFKLACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVEL
>LOXHD1_monBre_PLAT:09 Monosiga brevicollis (monosiga)
RTYRVKVHTGDQKGAGTDANVYVNLHGSLGDSGDRHLKNSLTHTNKFQRKTVDEFDIDAVTLGDINKVKVWHDNAGLGAAWYLEKIEVVDTADDKTYIFPCAQWFAKSMGDGQIAREL
>LOXHD1_monBre_PLAT:10 Monosiga brevicollis (monosiga)
FKYRISVHTSDVKHAGTDANVDIVLYGEKGDTGKIRLAKSETHRDMWERGNCDVFTVSAIELGDLKRVDIMHDGKGVGSGWHLNKVVVDAPQAGKTWTFMCDAWLDKATDDGTMAK
>LOXHD1_monBre_PLAT:11 Monosiga brevicollis (monosiga)
VPYEIIIKTSDVRNAGTDANVFIDLYGRDQEERDLTAHHEFKDAVKAHFERNLEDRFNVELPDVGSIYKIRLGHDGKGMSSSWHVASVVVINQRTHERFEFPCDAWLSKDKDDKKLVREFAVG
>LOXHD1_monBre_PLAT:12 Monosiga brevicollis (monosiga)
AIYKIHVFTGDIKHAGTDANIYVQIFGDTGDSGEIKLEKSETYRDKFERGHEDIFTHRCLDLGPLRKIKVRSDGKGLMGGDWYLDRVEVHQENDLSEPPVRFVCQDWFKRGKQEGDTLEREITAQ
>LOXHD1_monBre_PLAT:13 Monosiga brevicollis (monosiga)
LEYKVTVYTGTDTQAGTTANVWLQLFGEKDAPLTPAPPSPSKLSRSGSLFGRRRRASSDAQSVSSSLSAGASGPRETSTGRLQLNNAPADLQSGAKTTFTVTGLDVGELVGLEIGHDDERDKWYLEQVVVEVPKSATHAARRYEFKAGVWLAARADGSTSGSAK
>LOXHD1_monBre_PLAT:14 Monosiga brevicollis (monosiga)
LEYTLKVYTASADGAGCTAVPQVQLFGDKHTTEALPLRAGGDILPASVVETQHRVPDLGALLKVRLMVPRGSSWTVEKVEFGRAGQTPITFVGSDGSAVTLGAERLS
>LOXHD1_monBre_PLAT:15 Monosiga brevicollis (monosiga)
TSYRVYVTTADERGTGTDANVSIILYGAMGDSGEHSLTKSETFDDPFERGNTDVFTLEVPDLGELQRARIWHDGKGMFSSWKLDKIVVVVEATQSRYELPCGQWLSKNKGDKQLTRDLAVASKR
>LOXHD1_monBre_PLAT:16 Monosiga brevicollis (monosiga)
GTYKLEVATDSRAGGGCKGPVRIMLLDAEKNQLPLTLEPPGGEFAPGSVEHLVFDNVMLLGPLTELRIRRKPSGASSRRGAEDDDEDDNEASGASSQSGSAVSPWHLEHIIVKHLQSGQSFVFKGPSKGLSRSRAKLSVHTEA
>LOXHD1_monBre_PLAT:17 Monosiga brevicollis (monosiga)
AQYEVAVTTGTERGAGTDSNVFVTLFGKNGDSGERALAKSKTFRNMFESGNTDVFDVECQDLGELTKIEVKSDLKGFGAAWQLDKIKVTRTGSQNSWQFKCDQWFDKKQGAEHTFSVA</span>


=== Reference PLAT:07 domains ===
=== Reference PLAT:07 domains ===
The seventh PLAT domain (human numbering) is unique among PLAT domains in having a large expansion in the middle of the domain. It is a unique signature of the LOXHD1 orthology class that would distinguish it from other poly-PLAT domain concatenates of independent origin. That issue is completely hypothetical because no other protein in any vertebrate genome contains more than a single PLAT domain. Indeed, the LOXHD1 gene is single-copy in all species that retain it (including teleost fish). Thus even with very ancient eukaryotic divergencs, the corresponding genes can be taken as straightforward human orthologs.
These other proteins consist of 10 genes, namely four polycystins (PKD1L2, PKDREJ, PKD1L1, PKD1), two RAB6 (DENND5B, DENND5A), and five arachidonate 5-lipoxygenases (ALOX5, ALOXE3, ALOX15, ALOX12B, ALOX12) plus three bogus misannotations (AK310228, FLJ00285 and NPIP) found in many database compilations. In these other genes the PLAT domain occurs in the context of GPS-TM-PLAT-TM (polycystins), RUN-LH2-RUN (RAB6), and N-terminally (lipoxygenases).
Presumably a loop out of the beta barrel, it consists of an extremely high AG content at the dna level and encodes charged residues, primarily lysine K and glutamate E residues. These are asymmetrically distributed with the lysines N-terminal and the glutamates distal. The region is called the KE loop of PLAT:07 in this article.
Despite minimal net charge, this region may not be able to interact with (hydrophobic) membranes. Yet the split PLAT domain retains the potential to form a standard beta barrel. The region is quite variable even within mammals and must be hand-annotated to ensure accuracy (because its quasi-repetitive nature wreaks havoc with alignment). This section uses comparative genomics within eukaryotes to answer the following questions:
* when did the high GA section arise in phylogenetic time?  [early eukaryotes]
* what is its source?                                      [internal expansion, replication slippage]
* did it arise from intron or retroposon retention?        [species lacking the repeat also have a single exon]
* can the boundaries of 7th PLAT domain be better located?  [conservation on both sides of the KE region allow definition of the PLAT domain segments]
* is the 44-species alignment accurate in this region?      [corrections are needed when longer than human, eg platypus]
* does the KE domain disrupts PLAT function?                [evidently not: the split domain is highly conserved and can form a normal beta barrel]
* is it a mammalian innovation or an unwanted intrusion?    [this ancient expansion has variable expansion and contraction in different clades]
homSap LEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLRQLLKKERLKAKLQRKKKKRKGSDEEDEGEEEESSSSEESSSEEEEMEEEEEEEE  FGPGMQEVIEQHKFEAHRWLARGKEDNELVVELVPAGKPGPE 1
ornAna LEATDVGEIYKVRLGHSGEGFGSGWFIESLVLKRLVLKEVEPNPEEEKRKAKERERAREQRRKERLKAKQQRKKKKKMKKSSDDEDSEAEDSEEEEGSSEEESSSSSSEEEVEEEFGPGIKEVIDVYKFEAHRWLARDEDDKELIVELEPANRPGPE 1
galGal VEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKMDETD    KKKKKKKKKSEEEEEEEE                                                  TKVEEVMDVYTFVAHRWLAKDEGDKELVVELVPDGESELE 1
taeGut REAADVGKIYKIRIGHDGTGIGDGWFLESVTLKRLATKTEGSD    KKKKKKKKSEEEETKE                                                        EEGMDVYTFVAHRWLAKDEGDKELVVELVPDGESDLE 1
anoCar VEAVDVGKVYKIRIGHDGKGFGDGWFLDSVVVKKLPTKVP        KKKKKKKKKKTPEEEEAEE                                                    GPGIMEVYNFTPCRWLASDEEDKELVVELVPDEGSELE 1
oryLat IEALDVGKIYKIRIYHDGSGIGDGWFLETVDIKRLTMALVQVEV    KKEEAPKKDKKKDKKKKKKEEEEVEIIEE                                          MQEVVETFTFTCNRWLARDEEDGEIVVELLTEENEDLE 1
gasAcu IEAKDVGKIFKIRIGHDGSGIGSGWFLETVDVKRLILALVPKEK    KKEDKKKKKKKKEDVDEEGGEE                                                MQEVVLTYSFPCSRWLAGGEEDGELVVELLPDDAKELE 1
takRub IEAKDVGKIFKIRIGHDGLGIGSGWFLEKVYVKHLIMALVPREN    KKDDKKKKKKKKKDKEDEEEVGGEE                                              MQEVVVTYHFPCSRWLASGEDDDDLVVELLPEDAEELE 1
petMar VEAMDVGKVVKLRVGHDNSGMGSGWFLDSIVIRRLRQSSPHRPQPVDA              EEDEDEEDDEEAEDED                                            VQTYTFPCKRWLARDEDDGEIVRELLPQDCAEME 1
sacKow IEAADVAMLTKIRIGHDNSGRSAGWYLERVIIERFPPKRKM          KRKRSGTPRRRGEYDEEDYDD                                              IPETNVVNFVCNRWFAKDEEDHQIVRELLPTDEEALKGH 1
triAdh VECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKET    DEREEETAKKDADEPEKLDE                                                      NNYLFVANRWLSKEEGDRQTVIEISPVGVDGALA 1
monBre LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQAR                                                                                      IYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDN 1
  >PLAT:07_homSap Homo sapiens (human)
  >PLAT:07_homSap Homo sapiens (human)
  2 LVHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQ 0
  2 LVHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQ 0
Line 566: Line 820:
  0 LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDNGREVVEELALDANKRTYR 1
  0 LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDNGREVVEELALDANKRTYR 1


'''See also:''' [[USH2A_SNPs|Usher: USH2A]] | [[CDH23_SNPs|Usher: CDH23]] | [[Opsin_evolution:_RBP3_%28IRBP%29|RBP3 (IRBP)]] | [[Opsin_evolution:_RPE65|RPE65]] | [[Opsin_evolution:_transducins|Transducins]]


[[Category:Comparative Genomics]]
[[Category:Comparative Genomics]]

Latest revision as of 16:44, 27 December 2009

See also: Usher: USH2A | Usher: CDH23 | RBP3 (IRBP) | RPE65 | Transducins

Introduction

LoxConcat.jpg
Loxhd1OHC.jpg

LOXHD1, a large mis-annotated autosomal gene consisting solely of 16 concatenated 120-residue PLAT domains (named for polycystin/lipoxygenase/alpha-toxins), recently surfaced as a causative gene for age-progressive postlingual non-syndromic hearing loss type DFNB77. Of nearly a hundred known deafness genes, only MYO3 (myosin IIIA) and DFNB59 (protein product pejvakin -- echo in Persian) share this autosomal recessive progressive phenotype.

Howver there is no evidence to suggest that the three encoded proteins physically interact within auditory hair cells nor that heterozygotic combinations give rise to digenic disease (as argued in Usher Syndrome). Further, with larger numbers of pedigrees, each might exhibit syndromic effects (eg affect vision or kidney function).

Mouse knockouts have not been studied; delicate auditory hair cells may just be exquisitely sensitive detectors of subtle disruptions of gene function. While LOXDH1 is specific to hair cell stereocilia within the cochlea, GenBank transcripts also imply expression somewhere within testis, placenta, hippocampus, cerebellum cortex, medulla, stomach, liver, lung, and bone marrow. The protein has not been ultrastructurally localized in any of these other tissues.

LoxHippocampus.jpg

Some of these transcripts are exon-skipping, for example AK302484 disables the 12th PLAT domain though retains downstream reading frame. It's unclear whether such transcripts are functional or just splicing error inevitable in a giant protein (41 exons, 2273 amino acids) and merely destined for immediate turnover. The skipped exon, LGHDGASPESCWLVEELCLAVPTQGTKYML NCNCWLAKDRGDGITSRVFDLLDAMVVNIGVK, is still 72% conserved from human to shark; nothing other than functionality could explain such conservation.

Mutations do not surface during cochlear development but rather in mature stereocilia, which degenerate over time. LOXDH1 binds to the inner plasma membrane of stereocilia, perhaps organizing protein binding there or stabilizing some aspect of the membrane. As with other concatenated domain proteins (see CDC23 and USH2A, subtle dysfunction in one of many internally repeated domains surprisingly cannot be compensated for by the remaining intact domains.

Here the mouse I1342N disrupts the hydrophobic pocket between two beta sheets of the tenth PLAT domain but the protein is still made and localized properly. The first morphological change is observed at mouse day 21: fused stereocilia and membrane ruffling at the apical hair cell surface in the basal cochlear turn. Secondary effects arise later and include damage to spiral ganglion neurons.

Human allele R670* would eliminate all but the first five PLAT domains (of 16 total), possibly producing a normal but shortened protein, but might not produce protein at all due to nonsense-mediated decay. These individuals do not experience tinnitus, balance problems or vertigo, suggesting normal vestibular function even though LOXHD1 is expressed there too.

One difference between cochlear and vestibular hair cells is retention of the apical kinocilium in the latter. This is lost in developing cochlear hair cells as stereocilia mature. This correlates with peak LOXHD1 expression, suggesting to Grillet et al that LOXDH1 might help stabilize the stereociliary bundle in the absence of kinocilium.

Recall the kinocilium is a non-motile cilium-like structure present in the crista ampullaris of the semicircular ducts and the sensory maculae of the utricle and saccule but not in the cochlear duct organ of Corti (where in mammals it degenerates following maturation of the stereociliary bundle). Since retinal receptor cells are modified cilia and LOXDH1 functions most critically in microvillar hair cells after the kinocilium is gone, a syndromic effect extending to vision would not arise based on kinocilium/photoreceptor cilia homologization.

Phylogenetic occurence

The PLAT domain is quite ancient, readily tracing back to prokaryotes. However in other proteins it occurs only as single copy, often in conjunction with one or more catalytic domains. A common denominator in PLAT domain proteins is their association with lipid or membrane metabolism. This is perhaps mediated by extruded tryptophans which extend out from the standard beta barrel surface.

LOXHD1 itself has highly conserved orthologs throughout vertebrates, indeed deuterostomes (though the Branchiostoma gene model XM_002606291 contains other domains). These species all contain mechanosensory cells with ciliary F-actin based protrusions though expression has not be localized outside of mammals. No counterparts of the gene can be found in Ecdysozoa (strictly non-cilary mechanosensation) yet lophotrochozoa (Schistosoma and likely Aplysia) have full length counterparts, as can cnidrians (Hydra, Nematostella) though gene models at this time are fragmentary.

This establishes gene loss in the ancestral ecdysozoan, rather than gene innovation in Bilatera. However the overall impression is phylogenetically spotty occurence outside of deuterostomes. It's unclear whether some other gene product can compensate for lost LOXHD1 or whether it simply does not play an essential role.

Most surprisingly, full length orthologs of LOXHD1 with 17 PLAT domains and very similar intronation patterns are readily recoverable from early eukaryote genomes, notably Trichoplax and the choanflagellate Monosiga. This seems to rule out an obligatory association with F-actin-based mechanosensory organelles as the basal metazoan Trichoplax exhibits only 4 distinct cell types and the early animal Monosiga is unicellular.

Thus LOXDH1 is not even a metazoan innovation. Lateral gene transfer makes no sense in this context and is contradicted by the gene tree. The extraordinary conservation Monosiga to human -- surely in the 95th percentile of all genes -- establishes a long-selected intracellular role.

In the plant world, occurence is restricted to Chlamydomonas and Micromonas proteins (XM_001703369, XM_002502455) with 20 PLAT domains and numerous WD40 domains (ie not necessarily orthologous to animal pure poly-PLAT proteins). A curious note on the Chlamydomonas genbank entry states "identified by comparative genomics as being present only in organisms having motile cilia." Vertebrate kinocillia are non-motile.

Within deuterostomes, the large length of the gene does not sit well with gappy, incomplete and sometimes chaotic assemblies. Chicken, lamprey, amphioxus, tunicate and sea urchin are among the many that do not yield satisfactory full length gene models, in part because transcript support is limited to small regions of large proteins. However these species do contain long poly-PLAT proteins orthologous to human LOXHD1 (based on consecutive domains having consecutive best-blast).

Some of these unreliable sequences are provided in the reference sequence compilation below. Ironically, the obscure Monosiga and Trichoplax have better assemblies and more accurate gene models presumably because their genomes are much smaller.

Thus within vertebrates it is only feasible to compare selected PLAT motifs. Here there is a risk of using best-blast because significant cross-over matches will occur to other PLAT domains within the same protein, so some additional signature must be used for validation.

PLAT domain structure

The structure of three proteins containing single PLAT domains have been determined. The best blastp of human LOXHD1 to these is a coral lipoxygenase/allene oxidase natural fusion protein with PDB accession 3DY5. Lower quality but still useful matches occur with RAB6 (accession 3CWZ) and rabbit reticulocyte lipoxygenase (accession 2P0MA).

The basic structure of a PLAT domain consists of a sandwich of two 2-stranded beta sheets (beta barrel). The lipoxygenases are calcium-binding via extended pairs of acid residues and have conserved hydrophobic residues likely inserting into the plasma membrane but neither these nor the hydrophobic residues are conserved in LOXHD1.

The independently folding PLAT domain is sometimes denoted as LH2 or 'C2-like' depending on the structural publication and domain tool. This introduces confusion because SMART/Pfam/InterPro utilize very distinct HMM models for C2 and PLAT/LH2.

The secondary structure here is so generic that convergent evolution (non-homologous origins) must be considered, as with TIM proteins. Here however significant blastp matches at the primary sequence level unify PLAT and LH2 sequences to the exclusion of the entire C2 family. This agreement cannot have originated repeatedly by chance given the vast combinatorial space available to amino acid sequences.

Further, all PLAT/LH2 domains share characteristic conserved residues. Thus PLAT and LH2 domains are in fact all homologous (descended from a single source) and so multiplicity of domain names is inappropriate. PLAT is used here rather than LH2 (lipoxygenase homology) because the former is a more comprehensive acronym of protein classes containing the domain (lacking only lipases).

C2 domains bear an uncertain relationship to PLAT domains because a resemblance occurs only at the secondary and tertiary structural levels. The lack of convincing blastp of HMM profile matches could be due either to extreme divergence of primary sequence or to convergent evolution resulting in the same basic fold (and perhaps a similarly convergent hydrophobic intermediating function). If ever homologous, PLAT and C2 diverged in prokaryotic times.

The name C2 implies calcium binding yet even here some C2 domains function independently of calcium. It isnot clear whether calcium binding is ancestral or derived. If ancestral, it has not been resolved whether binding has been lost once or multiple times in different regions of the domain tree. While PLAT domains can be structurally aligned to C2 domains, that is potentially misleading and unnecessary given three determined structures for bona fide PLAT domains.

LOXHD1, which tracks back to the earliest unicellular animals, lacks capacity for calcium binding in all 16 of its domains in all descendant clades based on non-conservation of acidic liganding residues relative to coral lipoxygenase, human LOX5 and clostridial alpha-toxin PLAT domains.

AlleneLox.jpg

PLAT domain evolutionary history

LoxDomainTree.jpg

The human genome contains 20 other proteins with significant blastp matching to the PLAT domain of LOXHD1. These are shown below along with their flanking domains (GPS, RUN etc). After adjusting for gene expansions (paralogy), only 4 classes occur: polycystins, lipoxygenases, lipases, and RAB6-interacting. These all contain a single PLAT domain. The final column shows its best-blastp to LOXHD1; no strong pattern emerges though perhaps PLAT:09 may conserve the most ancestral features and PLAT:15 the least.

The first two columns at bottom shows the blastp score of a given human LOXHD1 PLAT domain averaged over it match to the 12 other genes; the second two columns show the average match of other genes over the 16 LOXHD1 PLAT domains.

The domain tree thus looks like ((((LOXHD1,RAB6Is),polycystins),lipoxygenases),lipases). A possible parsimonious evolutionary scenario postulates a single standalone PLAT domain originally serving as an auxillary protein to various enzymes with hydrophobic substrates. Later, copies fused with these catalytic domains in separate events with gain in efficiency.

PLATrates.jpg

Observe the PLAT domain is N-terminal to the catalytic domain of lipoxygenases but C-terminal to it in lipases and sandwiched internally by a repeated domain in RAB6I, indicating three separate fusion events. These fusion proteins then expanded copy number to the small paralogous gene families seen today. The individual PLAT domains then evolved at different rates, though they continued to share some common constraints (beta barrel, membrane fingers).

The standalone gene eventually expanded to a poly-PLAT protein; today the standalone domain itself is gone (no longer represented in extant species). It is not easy to discern intermediate events: each species seems to generate a unique internal domain tree (above). In other words, individual PLAT domains may have evolved at different rates in different clades, obscuring initial relationships from order of duplication.

Intermediate events may have included 1 domain tandemly duplicating to 2 and then to 4, 8, and finally 16 but other scenarios involving inhomogeneous recombination (and even higher multiplicities) are equally plausible. However the number of repeats has been very stable over many billions of years of branch length; each individual repeat seems important too in view of known point mutations.

LoxTrees.jpg
PKD1L1   GPS-TM-PLAT-TM  chr07:47780815  polycystin 1-like 1           pdb:3CWZ  PLAT:14 36%
PKD1     GPS-TM-PLAT-TM  chr16: 2078712  polycystin 1                  pdb:3CWZ  PLAT:01 38%
PKD1L2   GPS-TM-PLAT-TM  chr16:79691985  polycystin 1-like 2 signal    pdb:3CWZ  PLAT:11 35%
PKD1L3   GPS-TM-PLAT-TM  chr16:70556160  polycystic kidney disease     pdb:3CWZ  PLAT:01 40%
PKDREJ   GPS-TM-PLAT-TM  chr22:45030224  receptor egg jelly signal     pdb:3CWZ  PLAT:11 32%
DENND5A  RUN-PLAT-RUN    chr11: 9116949  RAB6 interacting 1            pdb:3CWZ  PLAT:09 42%
DENND5B  RUN-PLAT-RUN    chr12:31426424  RAB6 interacting 2            pdb:3CWZ  PLAT:09 37%
ALOX5    NH2-PLAT-lipox  chr10:45189635  arachidonate 5-lipoxygenase   pdb:2P0M  PLAT:01 37%
ALOX15       PLAT-lipox  chr17: 4480963  arachidonate 15-lipoxygenase  pdb:2P0M  PLAT:03 26%
ALOX12       PLAT-lipox  chr17: 6840108  arachidonate 12-lipoxygenase  pdb:2P0M  PLAT:09 30%
ALOX15B      PLAT-lipox  chr17: 7888129  arachidonate 15-lipoxygenase  pdb:2P0M  PLAT:02 34%
ALOX12B      PLAT-lipox  chr17: 7916679  arachidonate 12R-lipoxygenase pdb:2P0M  PLAT:09 29%
ALOXE3       PLAT-lipox  chr17: 7939943  arachidonate lipoxygenase 3   pdb:2P0M  PLAT:16 32%
LIPC     LIP-PLAT        chr15:56511467  lipase C                      pdb:2P0M  PLAT:11 30%
LIPG     LIP-PLAT        chr18:45342425  endothelial lipase            pdb:2P0M  PLAT:09 32%
LPL      LIP-PLAT        chr08:19840862  lipoprotein lipase            pdb:2P0M  PLAT:11 24%
PNLIP    LIP-PLAT        chr10:118295418 pancreatic lipase             pdb:2P0M  PLAT:16 24%
PNLIPRP1 LIP-PLAT        chr10:118340480 pancreatic lipase-related 1   pdb:2P0M  PLAT:16 27%
PNLIPRP2 LIP-PLAT        chr10:118370455 pancreatic lipase-related 2   pdb:2P0M  PLAT:01 31%
PNLIPRP3 LIP-PLAT        chr10:118177414 pancreatic lipase-related 3   pdb:2P0M  PLAT:02 27%

Loxtrichmono.jpg

Below all PLAT domains found in human proteins are aligned with the 16 domains of human LOXHD1. The coral lipoxygenase is included because it provides the template for beta strand assignment and locating the problematic calcium binding and hydrophobic extended residues. The lower alignment is just with human LOXHD1 domains and uses an optimized seventh PLAT domain (the KE expansion is removed).

PLATalignments.jpg

Individual PLAT domains can be quite conserved over the mammalian time scale. That is illustrated by a difference alignment of the fifth PLAT domain in 40 vertebrates (human to lamprey) below. Note columns where human sequence represents a unique change -- such as H->R in column 5 -- may be minor alleles or disease variants rather than the predominate residue in the overall human population. 

 01.hg18_6  MARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPSDSSATLK
 02.panTro  ....R..............................................................................................................................
 03.gorGor   S..R...........................................................................--------------------------..................G......
 04.ponAbe  ....R..............T.....................................................................................-....................N....
 05.rheMac  ....R.........................................................................................................................N....
 06.calJac  ....R...........................................................K.............C...............................................N....
 07.micMur  ....R...........................................................M.............................................................N....
 08.otoGar  ....R.                                              ............K.................-..........H.P.V.......T....................N....
 09.tupBel   ...R...........................................................K............A................................................N....
 10.mm9_6_  ....R...........................................................K.....V.......................................................N....
 11.rn4_6_  ....R...........................................................K.....V........................................Q...................
 12.dipOrd  ....R.....................Y..................E..................K.....V.......S.S.............................................N....
 13.cavPor  ....R.......F.............Y...................................L.K.............................................................N....
 14.speTri  .V..R.....................Y......-.....-------------............K............P......E...L.....................................N....
 15.oryCun                                          ..........S.............K..........................................................TG.N....
 16.ochPri  ....R...........................................................K.............S....V..........................................N....
 17.vicPac   ...R.......V.............................I.....................K.................F.E.........................................N....
 18.turTru  ....R...........................................V...............K.....V...........F.......................---------...........N....
 19.bosTau  ....R.....................Y.....................................K.................F.E....................-....................N....
 20.equCab  ....R...........................................................K............A....F.E.........................................N....
 21.felCat  ....R...........................................................K............G....F.E.........................................N....
 22.canFam  ....R...........................................................K............G....F.E.........................................N....
 23.myoLuc  ...HR......D.R......S.....Y............T.K..DEM.Q...............K........T.V.G....F..................Y........................N....
 24.pteVam   ...R.........................................M.................K..........R.G....F.E.........................................N....
 25.eriEur  ....R.....................Y.....................................K............G....F.A..............M..........................N....
 26.loxAfr                          ..Y.......-..M.....................A..L.K............G......E.........................................N....
 27.proCap  ....R.....................Y..A.......M...........R.........A..L.K............A......E..............M...---...................NN....
 28.echTel  ....R.....................Y..........MF.....V..............A..L.K......M.....A......-...LKK.........K..G.G....................N...R
 29.choHof  .V..R.....................Y.........W.........M....S...Y...A..L.K.K.I.VG.....GN...F.E..............M....N...AR.Q.....I......G.N....
 30.monDom  ..Q.R..L...DI.....N.QAFV.....A......M.......MEICQ..........A..V.K......G.....K....F.VK..................N..F...Q..............NSR..
 31.ornAna  IVK.R...V..D.N......R.FI..I.........I.........T.........FV.A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
 32.galGal  VIK.R......MVS.S......FV..I..Q....D.V..K.I..VNK.........F..A..LKQ......G.....GS.....AK.I.........EA.....Y.....NE....I....V.AGE.PL..
 33.anoCar   IK.R...H..NVS.S....H.FA..I..Q....D.V.Q.SV.TVNK....S....I..A.NLKQ......G.....GS.....GK.I...D.....EAQ....Y.....NE....II...V.AGR.SL.E
 34.xenTro                                   ...F.IE.K..MNK.......D.I..A..LKQ.K....G.....G.C...M.K.V...D.K..TEAI....N..F.RNE...HII...V.AGD.QN.R
 35.tetNig   LK.RI.I...NVG.G....S.F.NII..L......SMITSK..VNK.....H...L....CLGR.S...VG...R.G.C..F..K.T.........SAI....F....HNE....I....V.AGDGRLF 
 36.fr2_6_  LIK.R..I...NVS.G....S.F.NVI..L.......MIMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M.........SAI....F....HNE....I....V.A       
 37.gasAcu  LIK.R..I...NVS.S....S.F.NVI..L.......MFMSK..VNK.....H...L....SLGQ.....VG...R.G.C..F..K.M...D.....LAT....F....RNE....I....V.AGDGRLF 
 38.oryLat   IK.R..I...TVS.S....S.F.NVI..L.......M.MSK..VNK.....H...L....WLGQ.....VG...R.G.C..F..K.M.........AAI....N....QNE....II...V.AGEG    
 39.danRer   VK.R...Y..DVS.S....H.F...I..L....D.S.I..K..INK..R......I..A.SIGP......G...R.G.C.....K.TI.....A..QA.....S..F.RNE....I....Q.FADGRLY 
 40.petMar   VK.L..IH..KHG.G......FV..Y.EQ....D.M..TS...VNK..R..V...V..C..LKR.T....G...R.GS...F..KIM.K-D.RRQCEE.....N....D.E....I....VAGGCQMLK 
 Consensus  ...yrvt..tg...g.gtda.v..cl.gd.gdtger.ly.crnn...fekgna...t..s.t$rk.r...!r...k.ggs..y$d.!lvre#.qpes.nv...c.r.l.k#k....l!...l.sgsnatlk

Expansion of the PLAT:07 domain

The seventh PLAT domain (human numbering) is unique domains in having a large compositionally simple expansion in the middle of the domain. It is a unique signature of the LOXHD1 orthology class that would distinguish it from other poly-PLAT domain concatenates of independent origin. That issue is completely hypothetical because no other protein in any vertebrate genome contains more than a single PLAT domain. Indeed, the LOXHD1 gene is single-copy in all species that retain it (including teleost fish). Thus even with very ancient eukaryotic divergencs, the corresponding genes can be taken as straightforward human orthologs.

Presumably a loop out of the beta barrel, the expansion consists of an extremely high AG content at the dna level and encodes charged residues, primarily lysine K and glutamate E residues. These are asymmetrically distributed with the lysines N-terminal and the glutamates distal. The region will be called the KE loop of PLAT:07 here.

Despite minimal net charge, this region may not be able to interact with (hydrophobic) membranes. Yet the split PLAT domain retains the potential to form a standard beta barrel. The seventh PLAT domain is quite variable even within mammals and must be hand-annotated to ensure accuracy (because its quasi-repetitive nature wreaks havoc with alignment). This section uses comparative genomics within eukaryotes to answer the following questions:

  • when did the high GA section arise in phylogenetic time? [early eukaryotes]
  • what is its source? [internal expansion, replication slippage]
  • did it arise from intron or retroposon retention? [species lacking the repeat also have a single exon]
  • can the boundaries of 7th PLAT domain be better located? [conservation on both sides of the KE region allow definition of the PLAT domain segments]
  • is the 44-species alignment accurate in this region? [corrections are needed when longer than human, eg platypus]
  • does the KE domain disrupts PLAT function? [evidently not: the split domain is highly conserved and can form a normal beta barrel]
  • is it a mammalian innovation or an unwanted intrusion? [this ancient expansion has variable expansion and contraction in different clades]
homSap LEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLRQLLKKERLKAKLQRKKKKRKGSDEEDEGEEEESSSSEESSSEEEEMEEEEEEEE   FGPGMQEVIEQHKFEAHRWLARGKEDNELVVELVPAGKPGPE 1
ornAna LEATDVGEIYKVRLGHSGEGFGSGWFIESLVLKRLVLKEVEPNPEEEKRKAKERERAREQRRKERLKAKQQRKKKKKMKKSSDDEDSEAEDSEEEEGSSEEESSSSSSEEEVEEEFGPGIKEVIDVYKFEAHRWLARDEDDKELIVELEPANRPGPE 1
galGal VEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKMDETD     KKKKKKKKKSEEEEEEEE                                                   TKVEEVMDVYTFVAHRWLAKDEGDKELVVELVPDGESELE 1
taeGut REAADVGKIYKIRIGHDGTGIGDGWFLESVTLKRLATKTEGSD     KKKKKKKKSEEEETKE                                                        EEGMDVYTFVAHRWLAKDEGDKELVVELVPDGESDLE 1
anoCar VEAVDVGKVYKIRIGHDGKGFGDGWFLDSVVVKKLPTKVP        KKKKKKKKKKTPEEEEAEE                                                    GPGIMEVYNFTPCRWLASDEEDKELVVELVPDEGSELE 1
oryLat IEALDVGKIYKIRIYHDGSGIGDGWFLETVDIKRLTMALVQVEV    KKEEAPKKDKKKDKKKKKKEEEEVEIIEE                                          MQEVVETFTFTCNRWLARDEEDGEIVVELLTEENEDLE 1
gasAcu IEAKDVGKIFKIRIGHDGSGIGSGWFLETVDVKRLILALVPKEK    KKEDKKKKKKKKEDVDEEGGEE                                                 MQEVVLTYSFPCSRWLAGGEEDGELVVELLPDDAKELE 1
takRub IEAKDVGKIFKIRIGHDGLGIGSGWFLEKVYVKHLIMALVPREN    KKDDKKKKKKKKKDKEDEEEVGGEE                                              MQEVVVTYHFPCSRWLASGEDDDDLVVELLPEDAEELE 1
petMar VEAMDVGKVVKLRVGHDNSGMGSGWFLDSIVIRRLRQSSPHRPQPVDA               EEDEDEEDDEEAEDED                                            VQTYTFPCKRWLARDEDDGEIVRELLPQDCAEME 1
sacKow IEAADVAMLTKIRIGHDNSGRSAGWYLERVIIERFPPKRKM           KRKRSGTPRRRGEYDEEDYDD                                               IPETNVVNFVCNRWFAKDEEDHQIVRELLPTDEEALKGH 1
triAdh VECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKET    DEREEETAKKDADEPEKLDE                                                      NNYLFVANRWLSKEEGDRQTVIEISPVGVDGALA 1
monBre LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQAR                                                                                      IYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDN 1

Introns relative to PLAT domains

Here it emerges that PLAT domains correspond to 2-3 consecutive exons with conserved phasing, allowing for potential alternative splicing that reduced domain count while not introducing premature stop codons. This may reflect the origin of the 16 PLAT domains by iterated inhomogenous recombination. (to be continued).

Reference sequences (intronated)

The sequences below are broken into individual exons with reading phase (codon overhang) indicated by 012. Alternating colors show odd and even numbered PLAT domains. The 7th domain (which contains the charged KE expansion loop in mammals) is shown in red. In some cases, the PLAT domains are numbered and exon phases are not indicated. In the case of poor quality but phylogenetically important sequences, an approximate sequence is shown. 

>LOXHD1_homSap_full 41 exons|2273 aa|chr18|span 179,559 bp|no signal peptide|no conserved cysteines|16 PLAT domains|EIW --> WNW mouse deafness
0 MMPQKKRRRKKDIDFLALYEAELLNYASEDDEGELEHEYYKAR 1
2 VYEVVTATGDVRGAGTDANVFITLFGENGLSPKLQLTSK 2
1 SKSAFEKGNVDVFRVRTNNVGLIYKVR 2
1 IEHDNTGLNASWYLDHVIVTDMKRPHLRYYFNCNNWLSKVEGDRQWCRDLLASFNPMDMPR 1
2 GNKYEVKVYTGDVIGAGTDADVFINIFGEYGDT 1
2 GERRLENEKDNFEKGAEDRFILDAPDLGQLMKINVGHNNKGGSAGWFLSQ 0
0 IVIEDIGNKRKYDFPLNRWLALDEDDGKIQRDILVGGAETT 1
2 AITYIVTVFTGDVRGAGTKSKIYLVMYGARGNKNSGKIFLEGGVFDRGRTDIFHIELAVLLSPLSRVSVGHGNVGVNRGWFCEK 0
0 VVILCPFTGIQQTFPCSNWLDEKKADGLIERQLYEMVSLRKKRLK 1
2 KFPWSLWVWTTDLKKAGTNSPIFIQIYGQKGRTDEILLNPNNKWFKPGIIEKFR 0
0 IELPDLGRFYKIRVWHDKRSSGSGWHLER 0
0 MTLMNTLNKDKYNFNCNRWLDANEDDNEIVREMTAEGPTVRRIMG 1
2 MARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGN 0
0 ADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLR 2
1 WLDKDKDDGQLVRELLPSDSSATLK 1
2 NFRYHISLKTGDVSGASTDSRVYIKLYGDKSDTIKQVLLVSDNNLKDYFERGRVDEFTLETLNIGN 0
0 INRLVIGHDSTGMHASWFLGSVQIRVPRQGKQYTFPANRWLDKNQADGRLEVELYPSEVVEIQK 1
2 LVHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQ 0
0 LEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLRQLLKKERLKAKLQRKKKKRKGSDEEDEGEEEESSSSEESSSEEEEMEEEEEEEEFGPGMQEVIEQHKFEAHRWLARGKEDNELVVELVPAGKPGPE 1
2 RNTYEVQVVTGNVPKAGTDANVYLTIYGEEYGDTGERPLKKSDKSNKFEQGQ 0
0 TDTFTIYAIDLGALTKIRIRHDNTGNRAGWFLDRIDITDMNNEIT 2
1 YYFPCQRWLAVEEDDGQLSRELLPVDESYVLPQSEEGRGGGDNNPLDNLALEQK 1
2 DKSTTFSVTIKTGVKKNAGTDANVFITLFGTQDDT 1
2 GMTLLKSSKTNSDKFERDSIEIFTVETLDLGDLWKVRLGHDNT 1
2 GKAPGWFVDWVEVDAPSLGKCMTFPCGRWLAKNEDDGSIIRDLFHAELQTRLYTP 1
2 FVPYEITLYTSDVFAAGTDANIFIIIYGCDAVCTQQKYLCTNKREQKQFFERKSASRFIVE 0
0 LEDVGEIIEKIRIGHNNTGMNPGWHCSHVDIRRLLPDKD 0
0 GAETLTFPCDRWLATSEDDKKTIRELVPYDIFTEKYMKDGSLRQVYKEVEEPLD 1
2 IVLYSVQIFTGNIPGAGTDAKVYITIYGDLGDTGERYLGKSENRTNKFERGT 0
0 ADTFIIEAADLGVIYKIKLRHDNSKWCADWYVEKVEIWNDTNEDEFLFLCGRWLSLKKEDGRLERLFYEK 0
0 EYTGDRSSNCSSPADFWEIALSSKMADVDISTVTGPMADYVQEGP 1
2 IIPYYVSVTTGKHKDAATDSRAFIFLIGEDDERSKRIWLDYPRGKRGFSRGSVEEFYVAGLDVGIIKKIE 0
0 LGHDGASPESCWLVEELCLAVPTQGTKYMLNCNCWLAKDRGDGITSRVFDLLDAMVVNIGVK 0
0 VLYEMTVWTGDVVGGGTDSNIFMTLYGINGSTEEMQLDKKKAR 2
1 FEREQNDTFIMEILDIAPFTKMRIRIDGLGSRPEWFLER 0
0 ILLKNMNTGDLTMFYYGDWLSQRKGKKTLVCEMCAVIDEEEMMEWTSYTVAVKTSDIL 1
2 GAGTDANVFIIIFGENGDSGTLALKQSANWNKFERNNTDTFNFPDMLSLGHLCKLRVWHDNK 1
2 GIFPGWHLSYVDVKDNSRDETFHFQCDCWLSKSEGDGQTVRDFACANNKICDELEET 1
2 TYEIVIETGNGGETRENVWLILEGRKNRSKEFLMENSSRQRAFRK 2
1 GTTDTFEFDSIYLGDIASLCVGHLAREDRFIPKRELAWHVKTITITEMEYGNV 2
1 YFFNCDCLIPLKRKRKYFKVFEVTKTTESFASKVQSLVPVKYEVIVTTGYEPGAGTDANVFVTIFGANGDTGKRELKQKMRNLFERGSTDRFFLETLELGELRKVRLEHDSSGYCSGWLVEKVEVTNTSTGVATIFNCGRWLDKKRGDGLTWRDLFPSV* 0

>Gallus gallus gappy genome,flawed XM_425221 15 PLAT domains
MKETKKNKAEEEEEEEEEEEEENEEVVEDVVEEAVEEDGEDESQQKKSKKKSKSEDSEDDGEVKKKKKKKKKTKRKEYSSEEEDDYERRKKKKKKGKKSK
EKKKKKGDKSKKGKKEDNFLELYEQELRDYHSDSSNATEDEYNKKKVYEVVTVTGDVRGAGTDANVFVTLFGEFGITPKTHLTSKSSTAFERSKTDVFRV
KTNNVGQIKKIRIEHDNTGLNAGWFLDRVIVTDMNRPHLRFYFPCNNWLSKEDGDGLYVRDLIGSLNPMDVPKINKYVVRVFTGEVSGSGTDADVFINIF
GEKGDTGVRKLDNDKDNFEKGAEDKFTLDAPNLGRLRKINIGHNNKGGSAGWFLAKVIIEDIGNKCVYQFPVGRWFALDEDDGKIQRDILVGGTEATGIV
YNVAVVTGDIRGAGTNSKIHVILHGSKGLKNSGTIFLEGGEFERARTDLFNVEIASLLSPLSRVTIGHDNCGVSSGWYCEKVVVYCPFTGIEQTFPCGKW
LDEDEGDGLIERELYEMVSLRQRRLKKNPWSLWIWTSDIKNAGTDATIFFQIYGDKGKSDEMKLDNNSDNFEAGQTDKFMIELPDLGTFYKLRIWHEKRN
PFAGWHLDKVTLLKTLTKDKYSFNCGRWLDINEDDNEIVRELPAEGSLVTEVMPVIKYRVTVCTGMVSGSGTDANVFVCLIGDQGDTGDRVLYKCINNVN
KFEKGNADEFFVEAVTLKQVRRVRIGHDGKGGSSGWYLAKVIVREEGQPESEAVEFPCYRWLDKNEDDGQIVRELVPAGESPLLKNVSYHISVKTGDIPG
ASSDSKVFIKLYGEKADTSKETLLVSDNDLGNYFERGRVDEFTIDTMDIGKINRILIGHDNVGLRSGWFLASVQITVPVQGRQYMFPCNRWLDKDEADGR
VEVEVYPSEILPIEKLINYEVSVVTGDVRAAGTNAKVFMQIYGETGKTELIILENRSNNFERGATDIFEVEAADVGKIYKIRIGHDGKGIGDGWFLESVT
LKRLATKMDETDKKKKKKKKKSEEEEEEEETKVEEVMDVYTFVAHRWLAKDEGDKELVVELVPDGESELEENTYEVHVLTGSVWGSGTDANVFLSIYGIE
RGDTGERQLKRSNNLNKFEKGQVDVFTIKAIDLGELKKLRIRHDNSGSSPSWFLERVEIVDLKESTTYYFPCQRWLAVEEDDGQIVRELVPVDEAFVKKD
SENDGQSLATLGLEQKAKSTTYIVKVKTGDKKNAGTDANVFITLYGSKDDTGIVSLKASKLNKNKFERGKIDEFTVESVDIGDLKKIKIGHDNAGNSNGW
FLEWVEIDAPSLGQCLKFPCGRWLDKSEDDGAIERFIFPAELQTTEYIPFVPYEITVYTSDIFGAGTDADVFIVLYGSDGICTQQKSLCLNKREQRMYFE
RNSVNQFIVELEDVGDIIEKIRIGHNGGGLNSGWHLDRVAIRRLLPNGKGSETITFPCERWLAKSEDDGEIIRELVPSDIFTEKLMKDGTLKQIEEEVED
PLEVHTYKISVFTGDIYGAGTDANVFLNIYGDLGDTGERKLSKSETNFNKFERGQSYDGERRSLSESSVSLSSLDSSGNPKEKKSRLVKSAEEGLLIPYH
ITVTTGTEYDSSTDSRVFIIIMGPQKVRTERLWLDLPEGKDEFADGSVEKFSVWGLDVGEIKKVEVGHDGATPESCWLMEELTIVVPTKGVMYNFVCKCW
LARDKGDGLTSRILNILDADCVNVGIKILYEVTVVTGDIESGGTDAGIFMTVFGSNGNTEEMQLDKNGDRFERGQEDSFIMEIADIAPLRKMRIRTDAKG
TRPDWFLERIVMRNLTNQEVATFTYGDWLSKVKNAKGSLVCEMPAMVNDEQMMEDTTYTIQVKTSDIGGAGTDANVSLILFGENGDSGTLALKESNKSNK
FERNQMDEFNFPNMLSLGDLCKVRIWHDNKAYEIVTVTSNREDAETKENIWIILEGKLGRSKEFLMENSSKKRRFERRGSTDTFQFSSKNLGDIAAICVG
HCPKDGKKSSAKADVYWHVKEIIITEMELCNKYFFRCNGKIPLRYKRRDYKVFECAKVIESFASKARSLVPVKYETIVVTGFEKGAGTDANVFITIFGLN
GDSGKRALKQKFRNLFERGKTNRFYLETLDMGELKKVRIEHDNSGLAPGWLVERVEITNSATGVTTIFPCGKWLDENRGDGLTWRELFPRY*

>LOXHD1_cioSav Ciona savigny approx gene model 15 PLAT domains 
0                                                                                             EVIVEDTKYDRTYTFPCDRWLSLYKEDCQLTRHLMAVSGRQS
1  KRTTFEITTVTGNGEKRGAGTDANVFLTMRGSKGVSPKLQLKSEYCSRRNTFERGQSDVFRVKSVNVGNLKRIRMEIDDTGFAPAWFLELQVVVVDLANPSQRIYFPCGQWLSDDEQLFRDL VGSSNPLAR
2  PKSVNAYVVHTFTGDVRGAGTDATVKITLFGDHGDSGQLVLDDSKNNFERARKDTFSLQCPHLGKIKKIRIGKGHDNGGVSPGWYLDKVVVDDTMMDCVYSFPCQRWFAK
3  DEDDGRITRELVAGVGEAGIPYQVQVFTGRFTSSCMGGRRVKSVQGKSILDGKFQRNRVDICDIESTTMLSPLDHIEIGHDNSGTGPGWYLEKVVITCPTNGCEQVFSCRKWLATDEGDGLISR QLYESKSLRK
4  QVVQSAWNCLIWTSDVRNAGTDANVFIQVYGENGKSDELPLDNETDNFETGQKDKFKINLPEIGCIYKLRVWHDDSNPFSGWHLDKIELEPIGGKKGDLYTFKCGKWLDTNEGDGEVIREIPST GPGVKR
5  PQPLVRYSVSVVTGDKRGAGTDANVSCCLYGRQGDTGNRPLTASKNNRNKFERGQLHLMLIIQTQHHRWLATDEDDGAIVRELTSEGSP
6  QLLNTSYHVAVKTGDIRGAGTDADVYIQIYGSDGDTGRLKLTRGENIRNKFERGRTDKFKLEATDIGRLERIYIGHSDSGIGAGWFLDGIEIDVPSSGMHYTFKANRWLASDEGDGKTEIELYPT QTR
7  QQDKLPYEITVATGDTLNAGTDAQVVLQLYGEDGKSEVMKLRNKTDNFERKAIDKFKIEAPDIGPITKIRIGHDGRGVGSGWFLDSVKIQRFVHKTSKRKKRRRGQNQSEVETYWFVCKRWFDKSEDDGQ
8  IIRELEYTVDVYTGDKYGAGTDSNVFLTLYGENGDSGERKLDKSVNINKFERNQVDSFKLKAADLSTLKKLKIRHDNSEIGSSWFVDRVEVKVKGETWVFPCQRWLSTKEDDGQIERTLVPV DATYQRLQQQKQGRKASIAVRDAIALET
9  KAQLTTYEVSVKTGDVWGSGTDANVYLTLFGEKDDSGINLKTSKTYRDKFERNHIDVFTVESADLGVLKKIKIGHDNAGLSPGWYLEYVEVDAASLGMKWRFPCGRWIAKDKDDGKLEKELHLAT DETVG
10 YAAKVPYEITVYTSEISGAGTDADVYVVLYGREGIATEQTSLCSSKDERKSRFNKKGIDTFVLELDDIGEVIEKLRIGHDGKGWGAGWHLDKVEVRRLLEGVKGSETSTFTCGRWLARDEDDGEIVRELVPT KIVKEQVTKSGKLKRSESKLD
11 DALKQQYKVHVFTGDVFRGGTDANVFITIFGENGDTGERKLLKSETNTDKFERGKEDIFKLDAVDLGKLFKVHIRHDNALIQPAWFLDRVEIEDTDTGSIYVFHCERWLAKNKEDGKIARSLYVV GYDGETSTRRSLATTKSGGSLGKKSILSDTIP
12 EGPAIPYTVKIETGSEEGSSCKAPAFIKIFGPSKKGTVSRRIPLEPYSGKFKRGTIETFNIEAIDVGSIKKIEIGHSSVDEEWFVESVMVNQPTLGKSYTFKCHKWFARSKDDGLVSRIFTTD DAEKLS
13 FKAKIPYEITLHTGNVDNAGTDCTITLSVYGSKGNSPDITVKKSEEDGVLLERGSIDTINVELDEIAPLKMVRVGHDGRGQRADWFCDKKTLSRELSASVGGRS
14 VLKKTNYKINVKTSNLRSAGTNANVSCIVFGTFGETGELKLKVSETHKNKFERDAMDTFTFQDKLSVGEPQKLRVWHDSKGFSSGWHLDHIEVCDESTQQKYMFPCGRWLADDEDDKQTIREL TCSNLDQ
15 AKEGGQYTATVRTSDKRDAAPNSDGWVILHGKMGKSRRMKLREGKLGRGKASTFKLDSNDLGALQKITLGLEGDNMGRWHVDDVVIENPSGGQFKFDCHAWVSNEDGTNTRGSNFDC TATKGRTISMS
16 SLLPVKYEVTVVTADEKGSGTDSNVSLTIYGTNGDSGKRPLKQRFRDLFERKQTDKFTLEILDLGDLTKVQIRLEHDDAGFNADWLCDNVTIRNPVSGQSWTFICREWIGLKKANQLFREVLPR

>LOXHD1_cioInt Ciona intestinalis XM_002122635 defective assembly; frag gene model 16 PLAT domains
EVIVEDTKYDRTYTFPCDRWLSLYKEDCQLTRHLMAVSGRQSKRTTFEITTVTGNF 
GEKRGAGTDANVFITLRGSKGVSPKLQLKSD 21 RHNTFERGNSDVFRLKSANVGNLKRVRVEIDENGFAPAWFLERVVVVDMSKPSQRIFFPCGQWLSDDEQLFRDLVGSTDPLARPKM     
NAYVVHVFTGDMRGAGTDAEVFITLYGGKKGQLSSGKIVLDGKFQRNRVDICDVESASMLSPLDHIEIGHDNSGSGPGWFLDKVVVTCPTNGCEQVFSCRKWFATDEGDGLTSRELYESKSLRKQVMQK
SAWNCLIWTSDVRNAGTDANVFIQVYGENGKSDEIALDNETDNFETGQKDKFKINIPEVGRMYKLRVWHDDSNPFSGWHLDKIVLEPVGGKKGSSYTFNCQKWLDTNEGDGQIIREIPATGPGVKRPQPL
VRYQVTVVTGDKRNAGTDANVFCCLYGRQGDTGNRPLEASKSNRNKFERGQSDEFTIEAVDLKSVNKVKIGHDDSGSGWHLKEIIVRDETNGESTVFPCDRWLATDEDDGAIVRELTSEGSPQLLNT
TSYHVSVKTGDMRGAGTDADVYIQIYGSDGDGRLKLHQGENIRNKFERGRTDRFKLEATDIGRIERIYIGHNDSGVGAGWFLDGVEIDVPSSGMHYTFKSNRWLASDEGDGKTEVELYPTQTRQQDKLL
PYEITVTTGDIMNGGTDAQVVVQLYGEDGKSEVIRLRNKTDNFERKAVDKFKIEAPDIGPITKIRIGHDGRGVGSGWFLDSVKIQRFVRKTSKRKKRRRESMVSNDQNEVETYWFVCRRWFDKSEDDGQIIRELVPTDESGKPIDEALQE
LEYSVDVYTGDKYGAGTDSNVFITLYGENGDSGERKLDKSDNINKFERNQVDGFKLKAADLSNLKKLKIRHDNSELGSSWFVDRVEVKVKGQTWVFPCQRWLSTNEDDGQIERTLVPVDVATYQRLQQKQGSGRKASVAVRDAIALETKAQL
TTYEVSVKTGDIRGSGTDANVYLVLFGENDDSGMINLKTSKTHRDKFERNHTDVFTVESADLGNLKKVKIGHDNAGLSPGWYLEYVEVDAPSLGMKWRFPSGRWIAKDKDDGKLEKELFLAMDETVGYAAK
VPYEITVYTSEVSGAGTDADVYVVLYGRDGMSTEKTSLCPTKDERKSKFNKKSVDTFVLELDDVGEVIEKLRIGHDGKGWGAGWHLDKVEIRRLLEGAKGSETYSFTCGRWLARDEDDGEIVRELVPTQLVQEKVTKS
QQYKVHVYTGDVFNAGTDANVYITIYGENGDTGERKLLKSETNTDKFERGKEDIFKIDAVDLGKLFKVHIRHDNALLNPSWNLNRVEVEDTDTGNRYVFHCERWLAKGKDDGKIVHVYTGDVF
IPYTVKIETGSDEGSSSTASAFIKIYGPSKKGKVSRRITLDPPSGKFKKGTVESFNIDAIDVGTIKKIEIGHTGVDDEWFIESVMINQPTLGKSFTFKCHKWLARSKDDGLTTRIFTIDDAEKLTYKAK
IPYEVTIHTGNVPNAGTDCLITMSVYGTKGNAPDITIKKSEEEGILLERGSVDVFNVEMEEIAPLKMIRISHDGRGQRQDWFCDKIELRNLNSGKVTVFPCDSWLSKKLGEKTLSRELSASVGGRSVLKK
TTYKLNVKTSNMRSAGTNANVSCIVFGTFGDTGELRLKESETHKNKFERDSLDVFTYQDKLSIGQLQKLRVWHDSKGFSSGWHLEYIEVVDESTQQKFMFPCNRWLADDEDDKQTIRELTCSNLDQATEGHTV
GQYTATITTGDKRDAASSCDGWIILHGKMGKSRRLKIRSGKMGRGKKSEVKLDAGDVGKMEAITLGLHDMGRWYVEDVTIETGNGGQYKFDCHAWVSNEDGTNTRGRTFECSATKGRTVSMSSLIP
IKYEVTVVTADEKGAGTDANVKLTIYGENGDSGSRALKQRFRDLFERKQTDKFTLEILDLGELTKIRLEHDDGGFNADWLCDHVIVRNPVIGQSWTFVCREWIGTKKAGQLFREVMPRSTG*

>Schistosoma mansoni (flatworm) XP_002576380 2301aa Bilatera|Platyhelminthes blast
0 MNLEDSTNDDYLKNSKSRFSFHRKEEKEHKGIICCGHNTCHLDRYNLISSVKPFTARPYTLYKVVLTTADVPGAGTSAQ 1
2 IYITLKGEWGSSTRQKLRKEKVPTRNLRFYFYPGSTNTFSVVSPDLGGLHSVFIE 0
0 HDSLRKSDSWLLESVQVFHPLTKKRYMFMCNHWFSLYKEDGLIARELFGIRSAKT 1
2 KYSIVTVTGDQEGSGTNSKVYITIYGRTGITPRIELSQENKSTGKDILCAPFGRGTSTKFIVKAPNVGAITNIRIKQDESGNEPHWFLERVVVTDMSYPQWTYYFHLSCWLSSKYGDGKSCRLVRGYREPTGTGV 1
2 ETEYKLTFYTSDQKDAGTTGEVYVKLYGEKDSSREIWVNSINQKNRRQPTSYHFTRGSTVEVYLPPCPQLGEITKLKVGHNRAGSSPSWFLNK 0
0 VIVDDLRMNRVFEFPCYAWITKPSETIIVCQKSIKKEEKEIIWQ 1
2 KIPLEIRLYTGDVPNAGTTAKVYL 12 HQKTTSENKEDVYTTPYIWLEDGNYDRNGVTLFSIDLPVPKFISPLSQLVIGHDNTGHSPSWFFDK 0
0 VQIYCPLNGVEQTFLYRKWLTSSKPGMKVEQILCEEKSLRKCTDK 1
2 KIPWEISVKTSPIANSYVTAAVSIIIFGSKDKTMKIQLDRSNLEVSSEWTKVSGNEVVEMFRPNVESKFRIYIKDIGIPCKLRIQHDNKGSNPNWHLQE 0
0 IVLTNLRTHEQYEFYCNRWLSTREDDGSILREIPAKGPGITNPLP 1
2 LYHYIIQIFTGNKPNSGTNANIFINIFGEKGDCGERWLGRSVNRNSELFQQNQ 00 MDEFVIEAVQLGSINKICIGHEERSPGYGWYLAKIVLTIKENPKYKLTFECYR 21 WFDVGEDDGQIVRELFAHSSLS 1
2 AIAYNVTVLTGTCRNAGTVANVFVHLYGLQGESKDMQLKHKETEITKFEAGKSEEFILACGKLGE 0
0 IKKIKIWHDSIAPHSGWFLDEVVVIDYFLGRRYVFHVNRWLAKNEADGLISLDLQPTSIINIER 1
2 KSSYEVIVKTGGRKYAGTDSHVYITMFGINSESKEYHLANSKTHNNKFEQNHEDLFN 0
0 LNAVGLGSLKKIRVRHTNTGIAPGWFLDYILIRESIEQKKMEYFFPCYQWLSATRLDGLVIRELSVASENIFERWKSGHDISDDSRLILE 1
2 DQSTIYHVRIHTGSQSNISSDANVQIQLYGDKDFTGNIRLYKAYYGKEDILVNKFQAGQIANFIVKAINIGNIKKIR 2
1 IEHDTAVGSARWFVERVEVEARKLGLLWKFECNRFITPQQPELILYPEPKDISFVKP 1
2 MTNYQIKTFTSDISGAETTSSVYIQLYGNDSLPSSIRRLHQNNDSEQRFQRNKIDTFYVELEELQEPFSKLRIWHNDKGSSTDWHLNKVEIRKIKTNQY 0
0 VFVTYIFPCNKWLSRNMDQAALERELIPSHMLQDQNGVLQFERQLSPKWLMNTYEVRITTGDKAYAGTDASVYITLFGENGDSGERKLTKSLTHRNKFERGQ 0
0 TDVFQLEIVDLGKINKVRIRHDNSGVNPSWYLSTIEVFNISKSQSVHGLKDQPNETHHLVKYIFNCEAWLSTEHDEKVLDRFFSAEIIKPQDLPGIVPKTSKDIVPHKLIQDLSQGKKALE 1
2 TIPYLITVITGSDRKAGTPGPVWISCVDKDKMNSEKFILCDCYNRTMLKRGTTRYFRFAGVKLNDLTEIQ 0
0 VGNDAPESPSMGWYIQSLYLSFPTIGKMYLFDCKEWLSTNRGNKKRTCNLKISNTNIVKFKP 1
2 KITYHLKITTANVKRAGTDCSINLQIFGTNGVTNCYILEKTSNRFAQGITDNISLEMEDVGKLLKMRIGHDNQ 0
0 GKNKHWNLSCVEVTVANTNQLYRFVYDDWLSLTYGKRKSLWADLPAMIGDTVQLK 1
2 ETCLDIFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNS 0
0 IDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCSEVYMNDSKGHRTIDQESIETLLTTADSMNISDLKDNPEGKL 1
2 VYEVVIETGNLKDSGTTCDAWIILEGKHGRSPKLELVNQVGNPILQINQMNTFQ 2
1 LPSFPLGDLETIRLGIQERNINKQTNPNDIQSQKWFCEKVSIKDPVSKRTYIFTIHQWLSVTPTSNLKKDVLVNYSKIIEDPYKKAFNELK 1
2 NKQTVMYKVSIYTGTKGCANTDANIFITMFSTTPGLNSGRIALKRENNNLFDRKQLDEFYVESIDL 1
2 ESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVSN* 0

>LOXHD1_triAdh Trichoplax adhaerens (trichoplax) Metazoa XM_002107971 17 PLAT domains blast
0 MSASLAMQELMSDPSGHFAPKPPPGRSKINRKRPQT 1
2 APGRQITTASKAPKLWRSSTYNEPNLKRRKFIVTLNHKKDISSISRNAPYANRAYTTAMATAARTYSNALNKGQQKEIIPIYNPLCDPHLNDYYARKFGLLNSRD 0
0 ESRKNRKQ 1
2 AGVAYQFGVKTGDKKGSDTDA 2
1 VYIQVIGTKDKIPKKRLFKKQETEKTERGNLFKFDKSTVEKFAVQHRDIGDPVKLIVE 0
0 HDGNEKRHGWFLEEITLTNIQSKKSWLFPCHKWLSKYEGDRKLCYELKPLAKAGKA 1
2 VYEVSVLTGDKRGAGTDANVSVTLFGKHTSSPKIQLLKS 2
1 SKHKNPFERNNTDEFKIRTRDVGKLSKIRIEHDNAGFGPGWFLDK 0
0 VIICNLEKPNVKYYCPCNQWLAKDVGDKSISRDLTAYTDPNAAPS 1
2 AYVYIVHTFTGNKRGAGTDANVYAVIFGDSGDTGEKRLDNSKNNFEKSR 2
1 KDTFKLSCSCVGKLERLRIRHDNTGLFAGWYLDKV 1
2 VVEDPQEQQSYTFYCRRWLSKTEDDGEICRDLIVSASGDDGDDSVAPK 1
2 GYPYHIHVTTSDVKNAGTDAEVYVVMHGEGKKSKELNSGKLVLANSEKKKNTFERAMTDIFHMECAEMLSPLTKLTVGHDNKGLAAGWHLDR 0
0 IVIDCPTTGIEQTFLCQQWLDRKAGDGLTERELVEAFDMRKTRRP 1
2 KQLWFAWIWTSDIRGAGTDANVSMQIYGDKGKSQEIKLGNNTDNFEQATLDKFK 0
0 LEIDQVGVPYKLRIGHDNSNAFPGWHLDKVKLENMNDKEQYLFNCNRWLSRSEEDNEIIRELPASGPNCPNYP 1
2 IVIYEVSVHTGNKMGGGTDANVFIKIYGELGDSGYRPLKSSKSHNNKFERNQVDVFHIEAVTLKALKKIKIGHDGNNP 1
2 GAGWFLDKVVIKELNGEASNEFPCNR 2
1 WLSKSEDDGQIVRELFLKSDTPLLK 1
2 TTSYHISVKTGDVRNAGTDANVFIQIFGAKDDTGRVRLKQSLNTSNKFERNRIDKFIIEAAQIGK 0
0 IEKIIIGHDGKGLGSGWFLDYIELDVPSVGRLYRFSCHQWFDSTEGDRKVERELYPSECIKSAA 1
2 KIPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFK 0
0 VECEDVGKLRKLRIGHDSAGMGSAWFLDK 0
0 VYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEISPVGVDGALA 1
2 EMTYTIRVITGNKFGCGTNANVFINMYGEEGDSGERQLKKSETHTDKFERNQ 0
0 EDVFKISCLSLGELKKIKIRHDNSGFRPAWFLDKVIIEVGESKYQFMCDRWLAKDEDDGQISRELLPQSDEQSRAEAIGASKDLQKK 1
2 VASTTYNVSVTTGDIKGAGTDANVHIVLYGEKDDTGLIHLKNSTTHSNKFERNQEDRFVVEAIDIGELKKIK 2
1 IGHDNKGGMAGWFLNKVEIDIPSLGRRLLFPCGRWIDKGKDDGALERELYPLNEAEETYRP 1
2 HIPYEVTVYTTDKRGASTGANVYVVIYGEENQTEQASLEPDKKRRKQYFKNGAIDKFVLE 0
0 LDDVGEEITKLRIGHDGKGWGAGWHLDKVEICRLLDGGKASKKFTFQCNRWLASDEDDGAIVRELVPSEIVEKSSKDGGQVKTKVTKPTDGLK 1
2 VKPYTIHVFTGDVDGAGTNANVFLTIFGESGDSGERKLAKSDTHYDKFERNQ 0
0 EDIFHIEAADLGRLFKVKIRHDNTGSLFSPAWFLNRIEIVDDENEETTAFPCERWLAKKKDDGKIDRTLFVKGWEGDTSSVATTRSK 1
2 ASFRSNSTDLGEMVSASGRRASSRKGPVMAPIDEK 1
2 CVPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVS 1
2 HNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAANAQVTSYTKPYELTIHTGDVQNA 1 
2 GTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIP 0
0 LELDDVGTIKKIRIGHDGKGSRTDWYLEK 0
0 ASIQRMDTLDMYMFRANQWFSKKIDDKKLVREIPAETSKEGATTIK 1
2 KINYVLSTHTSDKRGSGTDANVFVIIFGENGDSGEIALKKSETNWNKFEKGQTDVFLINDRLSLGRLQKLRIWHDNA 1
2 GFGASWHLASVDIVDESTGVKYTFPCDKWLSKSNGDKLILRELPCAETAGNTAASKATKQESKSGKA 1
2 EYEIAFTTGTEKRAGTNQDVAIVLKGKSEKSREFLIENNEDKKYFSKGKTNKFTYTCKPLGDITKAIVSHRESAIGEEPDSKNSSWYLKVVTVVHKASGTT 2
1 YKFPCNKWIDLDDDEENNSSVTLKCKSADVAASSKAKPV 1
2 ELKPVKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* 0

>LOXHD1_triAdh Trichoplax adhaerens (trichoplax) Metazoa XM_002107971 17 PLAT domains blast
   MSASLAMQELMSDPSGHFAPKPPPGRSKINRKRPQTAPGRQITTASKAPKLWRSSTYNEPNLKRRKFIVTLNHKKDISSISRNAPYANRAYTTAMATAARTYSNALNKGQQKEIIPIYNPLCDPHLNDYYARKFGLLNSRDESRKNRKQAG
01 VAYQFGVKTGDKKGSDTDAVYIQVIGTKDKIPKKRLFKKQETEKTERGNLFKFDKSTVEKFAVQHRDIGDPVKLIVEHDGNEKRHGWFLEEITLTNIQSKKSWLFPCHKWLSKYEGDRKLCYE LKPLAKAGK
02 AVYEVSVLTGDKRGAGTDANVSVTLFGKHTSSPKIQLLKSSKHKNPFERNNTDEFKIRTRDVGKLSKIRIEHDNAGFGPGWFLDKVIICNLEKPNVKYYCPCNQWLAKDVGDKSISRD LTAYTDPNAAPSA
03 YVYIVHTFTGNKRGAGTDANVYAVIFGDSGDTGEKRLDNSKNNFEKSRKDTFKLSCSCVGKLERLRIRHDNTGLFAGWYLDKVVVEDPQEQQSYTFYCRRWLSKTEDDGEICRDLI VSASGDDGDDSVAPKG
04 YPYHIHVTTSDVKNAGTDAEVYVVMHGEGKKSKELNSGKLVLANSEKKKNTFERAMTDIFHMECAEMLSPLTKLTVGHDNKGLAAGWHLDRaIVIDCPTTGIEQTFLCQQWLDRKAGDGLTERELVEA FDMRKTRRPK
05 QLWFAWIWTSDIRGAGTDANVSMQIYGDKGKSQEIKLGNNTDNFEQATLDKFKLEIDQVGVPYKLRIGHDNSNAFPGWHLDKVKLENMNDKEQYLFNCNRWLSRSEEDNEIIRELPAS GPNCPNYPI
06 VIYEVSVHTGNKMGGGTDANVFIKIYGELGDSGYRPLKSSKSHNNKFERNQVDVFHIEAVTLKALKKIKIGHDGNNPGAGWFLDKVVIKELNGEASNEFPCNRWLSKSEDDGQIVRELFLK SDTPLLKT
07 TSYHISVKTGDVRNAGTDANVFIQIFGAKDDTGRVRLKQSLNTSNKFERNRIDKFIIEAAQIGKIEKIIIGHDGKGLGSGWFLDYIELDVPSVGRLYRFSCHQWFDSTEGDRKVERELYPS ECIKSAAK
08 IPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFKVECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEIS PVGVDGALAE
09 MTYTIRVITGNKFGCGTNANVFINMYGEEGDSGERQLKKSETHTDKFERNQEDVFKISCLSLGELKKIKIRHDNSGFRPAWFLDKVIIEVGESKYQFMCDRWLAKDEDDGQISRELLPQ SDEQSRAEAIGASKDLQKKVAS
10 TTYNVSVTTGDIKGAGTDANVHIVLYGEKDDTGLIHLKNSTTHSNKFERNQEDRFVVEAIDIGELKKIKIGHDNKGGMAGWFLNKVEIDIPSLGRRLLFPCGRWIDKGKDDGALER ELYPLNEAEETYRPH
11 IPYEVTVYTTDKRGASTGANVYVVIYGEENQTEQASLEPDKKRRKQYFKNGAIDKFVLELDDVGEEITKLRIGHDGKGWGAGWHLDKVEICRLLDGGKASKKFTFQCNRWLASDEDDGAIVRELVPS EIVEKSSKDGGQVKTKVTKPTDGLKV
12 KPYTIHVFTGDVDGAGTNANVFLTIFGESGDSGERKLAKSDTHYDKFERNQEDIFHIEAADLGRLFKVKIRHDNTGSLFSPAWFLNRIEIVDDENEETTAFPCERWLAKKKDDGKIDRTLFVK GWEGDTSSVATTRSKASFRSNSTDLGEMVSASGRRASSRKGPVMAPIDEKC
13 VPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVSHNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAA 
14 NAQVTSYTAGTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIPLELDDVGTIKKIRIGHDGKGSRTDWYLEKASIQRMDTLDMYMFRANQWFSKKIDDKKLVREI PAETSKEGATTIKK
15 INYVLSTHTSDKRGSGTDANVFVIIFGENGDSGEIALKKSETNWNKFEKGQTDVFLINDRLSLGRLQKLRIWHDNAGFGASWHLASVDIVDESTGVKYTFPCDKWLSKSNGDKLILREL PCAETAGNTAASKATKQESKSGK
16 AEYEIAFTTGTEKRAGTNQDVAIVLKGKSEKSREFLIENNEDKKYFSKGKTNKFTYTCKPLGDITKAIVSHRESAIGEEPDSKNSSWYLKVVTVVHKASGTTYKFPCNKWIDLDDDEENNSSVTLKC KSADVAASSKAKPVELKP
17 VKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* 

>Monosiga brevicollis (monosiga) Eukaryota|Choanoflagellates XM_001742822 17 PLAT domains blast exons colored; PLAT domains numbered
   MADLPVPTTALQRLQLERSRYSFAAADPPPSFVQRYTSADVLSHRLYAQGLASDVGPGSHSSLGMSRRVELPPYNPLNDPALANYFARKFEWNSTRSVGAGSGSRRSASASLTRTRQPVRGASAHGHTKSRTKSSHRK
01 GHASLEIFTSKRSNPVSKSEKYITVVGTKGRSDAIQLAAPGVHFRAGNKDVFQVNLTGIGKPTKVILENTGTKRTDGWCVSKVVLVKKTDKGTRRYRFSGPVWLSKHHDEMKLKR         VLHIDDEDIGSG
02 NGYRIDCYTGDVANAGTDAVATIQLFGSKGQSPMVELRRSDGQAFQRARVATFTLDDLANLGKLKKLVISHNGHGMASGWFLDKIIVTSLSSNKATVFPCDAWLDRKNGRSKELVAR       TAAAGAEGM
03 TTFTIRVMTGDRRGAGTDANVQCTLFGEDGESGPHTLNTSRNDFRRGHTDVFAVSSRKIGTLKRLRIWHDNGGAGPAWFLDAVEVVDEASGQTYRFECNRWLAKDEDDGQISRELTCN      GDSSWGL
04 KSYKLTIFTGDKRNAGTSANVFCKLVGERGASDNVILENSSKNFQRDRTDIFTVEASDLGSLRHIVLGHDNHGMGAGWYVERFSLEVPSEGKLYNVDVKQWFATDMSDGAIERTFRLD      NAETLDIAQR
05 LDWKCTIYTSDVANAGTDANVFMQVYGKKGKTDVVPLKNKSDTFERGQTDELRVQLINVGSLRKLRVWHDNKGMASGWHLDRIVLSRDGEEYIFPCAEWLAVSEGDKEIVRELPAT        GPNVKKPLQL
06 VEYTVRVATGHARFAGTNADVFVMLTGELGDSGKRALLRSQTNRNKFERGKEDVFTVAAVDLGKLTSVTVGHNNAGTSAGWFLDKIVVLDPRRGEEEEFPCHRWLAVDADDGQIERELVPK   MAEHQAAAT
07 TTYIVKIKTGDVRHAGTDANVFVQLFGKTGESTQLKLRNSETYSDAFERNKMDIFKFELLDLGDLSRILVGHDNKGMGAAWFLDYVEVEVPSIRTRWKFPCSRWFSKSQDDGLTER        EIYAEKEAGEPMEEDVS
08 APYLFRFYTSDVAFAGTDANVSVVLYGDEGKTEELVVNNQSDNFERGKADDFKLACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVEL         PLRRIETVDDNGREVVEELALDANK
09 RTYRVKVHTGDQKGAGTDANVYVNLHGSLGDSGDRHLKNSLTHTNKFQRKTVDEFDIDAVTLGDINKVKVWHDNAGLGAAWYLEKIEVVDTADDKTYIFPCAQWFAKSMGDGQIAREL      GVLEEQKPADFQTKNVG
10 FKYRISVHTSDVKHAGTDANVDIVLYGEKGDTGKIRLAKSETHRDMWERGNCDVFTVSAIELGDLKRVDIMHDGKGVGSGWHLNKVVVDAPQAGKTWTFMCDAWLDKATDDGTMAK        TLYASADAIEEYSAH
11 VPYEIIIKTSDVRNAGTDANVFIDLYGRDQEERDLTAHHEFKDAVKAHFERNLEDRFNVELPDVGSIYKIRLGHDGKGMSSSWHVASVVVINQRTHERFEFPCDAWLSKDKDDKKLVREFAVG EVKALEGDKVVRRESILSLQE
12 AIYKIHVFTGDIKHAGTDANIYVQIFGDTGDSGEIKLEKSETYRDKFERGHEDIFTHRCLDLGPLRKIKVRSDGKGLMGGDWYLDRVEVHQENDLSEPPVRFVCQDWFKRGKQEGDTLEREITAQ
   VDAAVAMKEATALEDEAARLQRKATTLSRKSTKGSPLRKGTGTTETNAELEEAQRQANIARRKADEAKERAGLAGADDTQ
13 LEYKVTVYTGTDTQAGTTANVWLQLFGEKDAPLTPAPPSPSKLSRSGSLFGRRRRASSDAQSVSSSLSAGASGPRETSTGRLQLNNAPADLQSGAKTTFTVTGLDVGELVGLEIGHDDERDKWYLEQVVVEVPKSATHAARRYEFKAGVWLAARADGSTSGSAK GKSKASVRLQPSEIHAGSERI
14 LEYTLKVYTASADGAGCTAVPQVQLFGDKHTTEALPLRAGGDILPASVVETQHRVPDLGALLKVRLMVPRGSSWTVEKVEFGRAGQTPITFVGSDGSAVTLGAERLS FDFLPAAAPASSGGKGKRRGSTTSSVAVAQQ
15 TSYRVYVTTADERGTGTDANVSIILYGAMGDSGEHSLTKSETFDDPFERGNTDVFTLEVPDLGELQRARIWHDGKGMFSSWKLDKIVVVVEATQSRYELPCGQWLSKNKGDKQLTRDLAVASKR VNALT
16 GTYKLEVATDSRAGGGCKGPVRIMLLDAEKNQLPLTLEPPGGEFAPGSVEHLVFDNVMLLGPLTELRIRRKPSGASSRRGAEDDDEDDNEASGASSQSGSAVSPWHLEHIIVKHLQSGQSFVFKGPSKGLSRSRAKLSVHTEA TTEEAVAQATKASV
17 AQYEVAVTTGTERGAGTDSNVFVTLFGKNGDSGERALAKSKTFRNMFESGNTDVFDVECQDLGELTKIEVKSDLKGFGAAWQLDKIKVTRTGSQNSWQFKCDQWFDKKQGAEHTFSVA S*

>LOXHD1_homSap_full dna: each line is an exon
ATGATGCCCCAGAAGAAAAGGCGGAGGAAGAAGGACATCGACTTCCTGGCCCTGTACGAAGCGGAGCTGCTGAACTACGCCTCGGAGGACGACGAGGGGGAGCTGGAACACGAGTACTACAAGGCCAGAG
TGTATGAAGTGGTCACAGCCACGGGGGATGTTCGCGGTGCAGGGACGGATGCCAATGTCTTCATCACGCTTTTTGGAGAGAATGGGCTCTCTCCCAAGCTCCAGCTCACCAGCAA
GAGCAAGTCTGCCTTTGAGAAGGGCAACGTCGATGTGTTCCGGGTGAGAACCAACAATGTGGGCCTCATCTATAAAGTCAG
GATTGAGCATGACAACACGGGCTTGAATGCCAGCTGGTACCTGGACCATGTGATTGTGACCGACATGAAGAGGCCTCATCTCCGTTACTACTTCAACTGCAACAACTGGCTGAGCAAGGTGGAAGGTGACCGCCAGTGGTGCCGTGACCTGCTGGCCAGCTTCAACCCCATGGACATGCCCAGAG
GTAATAAGTATGAAGTCAAGGTATACACTGGTGATGTAATTGGTGCAGGGACAGATGCTGATGTCTTCATCAATATTTTTGGAGAGTATGGAGACACAG
GGGAGCGTAGGCTAGAAAATGAAAAGGACAACTTTGAAAAGGGAGCTGAAGACAGGTTCATCCTGGATGCCCCGGATTTGGGGCAGCTGATGAAGATCAATGTTGGCCACAACAATAAGGGGGGCTCTGCAGGTTGGTTCCTGTCCCAG
ATAGTCATTGAAGATATTGGGAACAAAAGAAAATATGACTTCCCCCTTAACCGCTGGCTGGCCTTGGACGAAGACGATGGCAAAATCCAAAGGGATATCTTAGTGGGCGGAGCTGAGACCACAG
CTATTACGTATATTGTCACCGTCTTCACTGGGGATGTCCGGGGGGCTGGTACCAAATCCAAAATCTACTTGGTCATGTATGGGGCCAGAGGGAATAAGAACAGTGGGAAAATCTTCCTGGAGGGCGGCGTGTTTGACCGAGGCCGCACGGACATCTTCCACATCGAGCTGGCTGTCCTCCTTAGCCCCCTGAGTCGGGTCTCCGTCGGGCATGGCAATGTGGGTGTCAACAGAGGCTGGTTCTGTGAGAAG
GTGGTGATTCTGTGCCCCTTCACTGGTATCCAGCAGACCTTCCCTTGTAGCAACTGGCTGGATGAGAAGAAAGCGGATGGGTTGATTGAGAGGCAGCTCTATGAGATGGTGTCTCTCAGGAAGAAGCGGCTGAAAA
AATTCCCTTGGTCCCTGTGGGTCTGGACAACCGACCTAAAGAAAGCTGGTACCAACTCTCCCATCTTCATCCAGATTTATGGGCAGAAGGGGCGGACAGATGAGATTCTCCTGAATCCCAACAACAAGTGGTTCAAACCCGGCATAATCGAGAAGTTTAGG
ATTGAGCTCCCGGATCTTGGCAGGTTTTATAAGATTCGAGTATGGCATGATAAAAGGAGTTCTGGTTCTGGATGGCATTTAGAAAGG
ATGACCCTGATGAACACTCTGAACAAAGACAAGTACAACTTCAATTGCAACCGCTGGCTGGATGCCAATGAGGATGACAATGAGATAGTGAGGGAAATGACTGCAGAAGGCCCAACAGTGCGCAGGATCATGGGCA
TGGCCCGGTACCATGTGACTGTGTGCACAGGTGAACTTGAAGGTGCTGGGACCGATGCCAACGTCTATCTCTGCCTTTTTGGTGATGTGGGGGACACGGGGGAACGGCTGCTCTACAACTGCAGGAATAACACAGACCTGTTTGAAAAGGGCAAT
GCTGACGAGTTCACTATCGAGTCTGTCACCATGCGGAATGTGAGGCGGGTGAGGATCAGACACGATGGCAAAGGCTCCGGCAGCGGCTGGTACCTGGACAGAGTGCTGGTGAGAGAGGAGGGGCAGCCTGAGAGCGACAACGTGGAGTTCCCATGTCTCAG
GTGGTTGGACAAGGATAAGGATGATGGGCAGCTGGTCCGAGAGTTGCTACCCAGTGACAGCAGCGCGACACTGAAGA
ACTTTCGCTATCACATCAGCTTGAAGACTGGGGATGTCTCTGGGGCCAGCACGGATTCTAGAGTCTACATCAAGCTCTATGGGGATAAATCTGACACCATCAAGCAAGTTCTTCTTGTCTCTGACAACAACCTCAAAGACTACTTTGAACGTGGCCGGGTGGATGAGTTCACCCTCGAGACCCTGAACATTGGAAAT
ATCAACCGGCTGGTGATTGGGCATGACAGCACTGGCATGCATGCCAGCTGGTTCCTGGGCAGCGTTCAGATCCGTGTGCCCCGTCAAGGCAAGCAGTACACCTTTCCCGCCAACCGCTGGCTGGACAAGAACCAGGCTGACGGGCGCCTGGAGGTGGAGCTGTATCCCAGCGAGGTGGTGGAGATCCAGAAAT
TGGTCCACTATGAGGTTGAGATTTGGACAGGAGATGTGGGTGGCGCAGGCACCAGTGCCCGAGTCTACATGCAGATCTATGGAGAGAAAGGCAAGACAGAAGTGCTCTTCCTCTCCAGCCGCTCAAAAGTTTTTGAACGGGCGTCCAAGGACACATTCCAG
CTTGAGGCGGCCGACGTGGGCGAGGTCTATAAGCTCCGGCTCGGGCACACGGGCGAGGGCTTTGGGCCCAGCTGGTTCGTGGACACCGTGTGGCTGCGGCACCTGGTGGTGCGGGAGGTGGACCTCACGCCGGAGGAGGAGGCCCGGAAGAAGAAGGAGAAGGACAAGCTGCGGCAGCTGCTCAAGAAGGAGCGGCTGAAGGCCAAGCTGCAGAGGAAGAAGAAGAAGAGGAAGGGCAGCGACGAAGAGGACGAGGGGGAGGAAGAGGAGTCGTCCTCATCAGAGGAGTCCTCGTCAGAGGAGGAGGAGATGGAAGAAGAGGAGGAAGAGGAGGAGTTTGGGCCGGGGATGCAGGAGGTGATTGAGCAGCACAAGTTCGAAGCCCACCGCTGGCTGGCCCGGGGCAAGGAGGACAACGAACTTGTCGTGGAGTTGGTGCCAGCTGGCAAGCCGGGTCCTGAGC
GAAACACCTATGAGGTTCAGGTGGTCACGGGGAATGTGCCCAAGGCCGGCACTGATGCTAACGTCTACCTAACCATCTACGGCGAGGAGTATGGAGACACGGGCGAACGACCCCTGAAGAAGTCAGACAAGTCCAACAAATTTGAGCAGGGGCAG
ACAGACACCTTCACCATCTATGCCATTGACCTGGGGGCCCTGACCAAGATTCGGATTCGCCACGACAACACAGGCAACAGAGCAGGCTGGTTCCTGGACAGAATAGACATTACTGACATGAACAACGAGATCAC
GTACTACTTTCCATGCCAACGTTGGCTGGCAGTGGAGGAAGATGATGGCCAGCTGTCCAGGGAGCTGTTGCCAGTGGATGAGTCCTATGTGCTGCCACAGAGCGAGGAGGGTAGGGGAGGCGGTGACAACAACCCCCTCGACAACCTGGCCCTGGAGCAGAAAG
ATAAATCTACCACATTCTCAGTGACCATAAAGACTGGGGTTAAGAAGAATGCGGGCACAGATGCTAATGTCTTCATCACACTCTTTGGCACACAGGATGACACTG
GAATGACCCTCCTGAAGTCCTCCAAGACAAACAGCGATAAGTTTGAGAGGGACAGCATTGAAATCTTCACGGTGGAGACGCTGGATCTGGGAGACCTGTGGAAAGTCCGGCTTGGCCATGACAACACAG
GCAAGGCCCCAGGCTGGTTTGTAGACTGGGTAGAGGTGGATGCCCCATCTCTTGGGAAGTGCATGACGTTTCCCTGTGGCCGCTGGCTGGCCAAAAACGAAGACGACGGGTCCATCATCAGAGACCTCTTCCATGCAGAGCTTCAGACGAGGCTGTACACACCAT
TTGTTCCTTACGAGATCACCCTCTACACCAGTGATGTCTTTGCTGCTGGGACAGATGCCAACATCTTCATCATCATCTATGGCTGCGATGCCGTGTGCACCCAGCAGAAGTATCTGTGTACCAACAAGAGGGAACAGAAGCAGTTCTTTGAGAGGAAGTCTGCCTCCCGCTTCATCGTAGAG
TTAGAAGATGTGGGAGAAATCATTGAAAAAATTCGGATTGGCCATAATAACACGGGCATGAATCCTGGGTGGCACTGCTCTCACGTGGACATCCGCAGGCTCCTCCCGGATAAAGAC
GGTGCAGAGACCTTGACTTTCCCATGCGATCGGTGGCTTGCCACCTCTGAGGATGACAAAAAGACCATTCGAGAACTGGTTCCATATGACATCTTCACTGAGAAATACATGAAAGATGGGTCCTTACGGCAAGTCTACAAGGAAGTAGAAGAGCCTCTGGACa
TTGTGCTGTACTCGGTGCAGATCTTCACAGGGAACATTCCTGGGGCAGGGACGGATGCCAAGGTGTACATCACCATCTATGGAGACCTCGGGGACACTGGGGAGCGATACCTTGGCAAGTCAGAGAACCGGACCAACAAGTTCGAGAGAGGAACG
GCTGACACCTTCATCATCGAGGCCGCTGACCTAGGCGTCATCTACAAGATCAAGCTCCGCCATGACAACTCCAAGTGGTGCGCAGACTGGTACGTGGAGAAGGTGGAGATCTGGAATGACACCAACGAGGACGAGTTCCTGTTCCTATGCGGGCGCTGGCTCTCCCTGAAGAAGGAGGATGGGCGACTCGAGAGGCTCTTTTACGAGAAG
GAGTACACTGGGGACCGCAGCAGCAACTGCAGCAGCCCTGCTGACTTCTGGGAGATCGCCCTGAGCTCCAAGATGGCCGATGTCGACATCAGCACAGTGACCGGGCCCATGGCTGACTACGTTCAAGAGGGCCCAA
TTATTCCCTACTATGTGTCAGTCACCACTGGGAAGCACAAGGACGCGGCCACTGACAGCCGAGCCTTCATCTTTCTCATCGGGGAGGATGATGAACGTAGTAAGCGCATCTGGTTGGACTACCCCCGAGGGAAGAGGGGCTTCAGCCGTGGCTCTGTGGAGGAGTTCTACGTCGCAGGCTTGGATGTGGGCATCATCAAGAAAATAGAG
CTGGGCCATGACGGGGCCTCCCCTGAGAGCTGCTGGCTGGTGGAAGAGTTGTGTTTGGCAGTGCCCACCCAGGGCACCAAGTACATGTTGAACTGTAACTGCTGGCTGGCCAAGGACAGAGGCGACGGCATCACCTCCCGTGTCTTCGACCTCTTGGATGCCATGGTGGTGAACATTGGGGTGAAG
GTTCTCTATGAAATGACGGTGTGGACAGGGGATGTGGTTGGCGGGGGCACTGACTCCAACATCTTCATGACCCTCTACGGCATCAACGGGAGCACAGAGGAGATGCAGCTGGACAAAAAGAAAGCCAG
GTTTGAGCGGGAGCAGAACGACACCTTCATCATGGAGATCCTAGACATTGCTCCATTCACCAAGATGCGGATCCGGATTGATGGCCTGGGCAGTCGGCCGGAGTGGTTCCTGGAGAGG
ATCCTACTGAAGAACATGAACACTGGAGACCTGACCATGTTCTACTATGGAGACTGGCTGTCCCAGCGGAAGGGCAAGAAGACCCTGGTGTGTGAAATGTGTGCCGTTATCGATGAGGAAGAAATGATGGAGTGGACCTCCTACACCGTCGCAGTTAAGACCAGCGACATCCTGG
GAGCAGGCACTGATGCCAACGTGTTCATCATCATCTTCGGGGAGAACGGGGATAGTGGGACACTGGCCCTGAAGCAGTCGGCAAACTGGAACAAGTTTGAGCGGAACAACACGGACACATTCAACTTCCCTGACATGCTGAGCTTGGGCCACCTCTGCAAGCTGAGGGTCTGGCACGACAACAAAG
GGATATTTCCTGGCTGGCATCTGAGCTATGTCGATGTGAAGGACAACTCCCGCGACGAGACCTTCCACTTCCAGTGTGACTGCTGGCTCTCCAAGAGTGAGGGTGACGGGCAGACGGTCCGCGACTTTGCCTGTGCCAACAACAAGATCTGTGATGAGCTGGAAGAGACCA
CCTACGAGATCGTCATAGAAACGGGCAACGGAGGCGAAACCAGGGAGAACGTCTGGCTCATCCTGGAGGGCAGGAAGAACCGATCCAAAGAGTTTCTCATGGAAAATTCTTCTAGGCAGCGGGCCTTTAGGAA
GGGGACCACAGACACGTTTGAGTTTGACAGCATCTACTTGGGGGACATTGCCTCCCTCTGTGTGGGCCACCTTGCCAGGGAAGACCGGTTTATCCCCAAGAGAGAACTTGCCTGGCATGTCAAGACCATCACCATCACCGAGATGGAGTACGGCAATGT
GTACTTCTTTAACTGTGACTGCCTCATCCCCCTCAAGAGGAAGAGGAAGTACTTCAAGGTATTCGAGGTTACCAAGACGACAGAGAGCTTTGCCAGCAAGGTCCAGAGCCTGGTGCCCGTCAAGTACGAAGTCATCGTGACAACAGGCTATGAGCCAGGGGCAGGCACTGATGCCAACGTCTTCGTGACCATCTTTGGGGCCAACGGAGACACAGGCAAGCGGGAGCTGAAGCAGAAAATGCGCAACCTCTTCGAGCGGGGCAGCACAGACCGCTTCTTCCTGGAGACGCTGGAGCTGGGTGAGCTGCGCAAGGTGCGCCTGGAGCACGACAGCAGTGGCTACTGCTCAGGCTGGCTGGTGGAGAAGGTGGAGGTCACCAACACCAGCACCGGCGTGGCCACCATCTTCAACTGTGGCAGGTGGCTGGACAAGAAGCGGGGGGATGGACTCACCTGGAGAGACCTCTTCCCTTCTGTC

Reference PLAT domain sets

>LOXHD1_homSap_PLAT:01
RVYEVVTATGDVRGAGTDANVFITLFGENGLSPKLQLTSKSKSAFEKGNVDVFRVRTNNVGLIYKVRIEHDNTGLNASWYLDHVIVTDMKRPHLRYYFNCNNWLSKVEGDRQWCRD

>LOXHD1_homSap_PLAT:02
NKYEVKVYTGDVIGAGTDADVFINIFGEYGDTGERRLENEKDNFEKGAEDRFILDAPDLGQLMKINVGHNNKGGSAGWFLSQIVIEDIGNKRKYDFPLNRWLALDEDDGKIQRDILVGG

>LOXHD1_homSap_PLAT:03
ITYIVTVFTGDVRGAGTKSKIYLVMYGARGNKNSGKIFLEGGVFDRGRTDIFHIELAVLLSPLSRVSVGHGNVGVNRGWFCEKVVILCPFTGIQQTFPCSNWLDEKKADGLIER

>LOXHD1_homSap_PLAT:04
FPWSLWVWTTDLKKAGTNSPIFIQIYGQKGRTDEILLNPNNKWFKPGIIEKFRIELPDLGRFYKIRVWHDKRSSGSGWHLERMTLMNTLNKDKYNFNCNRWLDANEDDNEIVREM

>LOXHD1_homSap_PLAT:05
ARYHVTVCTGELEGAGTDANVYLCLFGDVGDTGERLLYNCRNNTDLFEKGNADEFTIESVTMRNVRRVRIRHDGKGSGSGWYLDRVLVREEGQPESDNVEFPCLRWLDKDKDDGQLVRELLPS

>LOXHD1_homSap_PLAT:06
FRYHISLKTGDVSGASTDSRVYIKLYGDKSDTIKQVLLVSDNNLKDYFERGRVDEFTLETLNIGNINRLVIGHDSTGMHASWFLGSVQIRVPRQGKQYTFPANRWLDKNQADGRLEV

>LOXHD1_homSap_PLAT:07
VHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQLEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLR

>LOXHD1_homSap_PLAT:08
NTYEVQVVTGNVPKAGTDANVYLTIYGEEYGDTGERPLKKSDKSNKFEQGQTDTFTIYAIDLGALTKIRIRHDNTGNRAGWFLDRIDITDMNNEITYYFPCQRWLAVEEDDGQLSRELLPV

>LOXHD1_homSap_PLAT:09
TTFSVTIKTGVKKNAGTDANVFITLFGTQDDTGMTLLKSSKTNSDKFERDSIEIFTVETLDLGDLWKVRLGHDNTGKAPGWFVDWVEVDAPSLGKCMTFPCGRWLAKNEDDGSIIRDLFHA

>LOXHD1_homSap_PLAT:10
VPYEITLYTSDVFAAGTDANIFIIIYGCDAVCTQQKYLCTNKREQKQFFERKSASRFIVELEDVGEIIEKIRIGHNNTGMNPGWHCSHVDIRRLLPDKDGAETLTFPCDRWLATSEDDKKTIRELVP

>LOXHD1_homSap_PLAT:11
VLYSVQIFTGNIPGAGTDAKVYITIYGDLGDTGERYLGKSENRTNKFERGTADTFIIEAADLGVIYKIKLRHDNSKWCADWYVEKVEIWNDTNEDEFLFLCGRWLSLKKEDGRLERLFYEK

>LOXHD1_homSap_PLAT:12
IPYYVSVTTGKHKDAATDSRAFIFLIGEDDERSKRIWLDYPRGKRGFSRGSVEEFYVAGLDVGIIKKIELGHDGASPESCWLVEELCLAVPTQGTKYMLNCNCWLAKDRGDGITSRVFD

>LOXHD1_homSap_PLAT:13
VLYEMTVWTGDVVGGGTDSNIFMTLYGINGSTEEMQLDKKKARFEREQNDTFIMEILDIAPFTKMRIRIDGLGSRPEWFLERILLKNMNTGDLTMFYYGDWLSQRKGKKTLVC

>LOXHD1_homSap_PLAT:14
TSYTVAVKTSDILGAGTDANVFIIIFGENGDSGTLALKQSANWNKFERNNTDTFNFPDMLSLGHLCKLRVWHDNKGIFPGWHLSYVDVKDNSRDETFHFQCDCWLSKSEGDGQTVRDFAC

>LOXHD1_homSap_PLAT:15
TTYEIVIETGNGGETRENVWLILEGRKNRSKEFLMENSSRQRAFRKGTTDTFEFDSIYLGDIASLCVGHLAREDRFIPKRELAWHVKTITITEMEYGNVYFFNCDCLIPLKRKRKYFKVF

>LOXHD1_homSap_PLAT:16
VKYEVIVTTGYEPGAGTDANVFVTIFGANGDTGKRELKQKMRNLFERGSTDRFFLETLELGELRKVRLEHDSSGYCSGWLVEKVEVTNTSTGVATIFNCGRWLDKKRGDGLTWRDLFPS

>PKD1L1_homSap_PLAT chr7: 47780815 polycystin-1L1 GPS-TM-LH2-TM pdb:3CWZ
QLYAVVIDTGFRAPARLTSKVYIVLCGDNGLSETKELSCPEKPLFERNSRHTFILSAPAQLGLLRKIRLWHDSRGPSPGWFISHVMVKELHTGQGWFFPAQCWLSAGRHDGRVERELTC

>PKD1_homSap_PLAT chr16: 2078712 polycystin 1 GPS-TM-LH2-TM pdb:3CWZ
FKYEILVKTGWGRGSGTTAHVGIMLYGVDSRSGHRHLDGDRAFHRNSLDIFRIATPHSLGSVWKIRVWHDNKGLSPAWFLQHVIVRDLQTARSAFFLVNDWLSVETEANGGLVEK

>PKD1L2_homSap_PLAT chr16: 79691985 polycystin 1-like 2 signal...GPS-TM-LH2-TM pdb:3CWZ 
YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSWYVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA

>PKD1L3_homSap chr16:70,556,160 GPS-TM-LH2-TM polycystic kidney disease 1-like 3
FHYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHHLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSWYVSQVIVCDMAVKRKWHFLCNCWLAVDLGDCELDRVFIPV

>PKDREJ_homSap_PLAT chr22: 45030224 receptor for egg jelly-like signal...GPS-TM-LH2-TM pdb:3CWZ
CYLVTIFTGSRWGSGTRANVFVQLRGTVSTSDVHCLSHPHFTTLYRGSINTFLLTTKSDLGDIHSIRVWHNNEGRSPSWYLSRIKVENLFSRHIWLFICQKWLSVDTTLDRTFHVT

>DENND5A_homSap_PLAT chr11: 9116949 RAB6 interacting 1 RUN-LH2-RUN pdb:3CWZ
LIHILIVPSKKLGGSMFTANPWICISGELGETQIMQIPRNVLEMTFECQNLGKLTTVQIGHDNSGLYAKWLVEYVMVRNEITGHTYKFPCGRWLGKGMDDGSLER

>DENND5B_homSap_PLAT chr12: 31426424 RAB6 interacting 2 RUN-LH2-RUN pdb:3CWZ
PYRSVIIPIKKLSNAIITSNPWICVSGELGDTGVMQIPKNLLEMTFECQNLGKLTTVQIGHDNSGLLAKWLVDCVMVRNEITGHTYRFPCGRWLGKGIDDGSLER

>ALOX5_homSap_PLAT chr10: 45189635 arachidonate 5-lipoxygenase NH2-LH2-lipox pdb:2P0M
PSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDG

>ALOX15_homSap_PLAT chr17: 4480963 arachidonate 15-lipoxygenase NH2-LH2-lipox pdb:2P0M
GLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPLLFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEG

>ALOX15_oryCun Oryctolagus cuniculus (rabbit) arachidonate 15-lipoxygenase 15S-LOX1 PDB:P0M
GVYRVCVSTGASIYAGSKNKVELWLVGQHGEVELGSCLRPTRNKEEEFKVNVSKYLGSLLFVRLRKKHFLKEDAWFCNWISVQALGAAEDKYWFPCYRWVVGDGVQSLPVG

>ALOX12_homSap_PLAT chr17: 6840108 arachidonate 12-lipoxygenase NH2-LH2-lipox pdb:2P0M
GRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLLQFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEG

>ALOX15B_homSap_PLAT chr17 7,888,129 arachidonate 15-lipoxygenase NH2-LH2-lipox pdb:2P0M 
AEFRVRVSTGEAFGAGTWDKVSVSIVGTRGESPPLPLDNLGKEFTAGAEEDFQVTLPEDVGRVLLLRVHKAPPVLPLLGPLAPDAWFCRWFQLTPPRGGHLLFPCYQWLEGAGTLVLQEG

>ALOX12B_homSap_PLAT chr17: 7916679 arachidonate 12R-lipoxygenase NH2-LH2-lipox pdb:2P0M
ATYKVRVATGTDLLSGTRDSISLTIVGTQGESHKQLLNHFGRDFATGAVGQYTVQCPQDLGELIIIRLHKERYAFFPKDPWYCNYVQICAPNGRIYHFPAYQWMDGYETLALREA

>ALOXE3_homSap_PLAT chr17: 7939943 arachidonate lipoxygenase 3 NH2-LH2-lipox pdb:2P0M
AVYRLCVTTGPYLRAGTLDNISVTLVGTCGESPKQRLDRMGRDFAPGSVQKYKVRCTAELGELLLLRVHKERYAFFRKDSWYCSRICVTEPDGSVSHFPCYQWIEGYCTVELRPG

>LIPC_homSap LIP-PLAT chr15:56511467 lipase C 
YHYQLKIQFINQTETPIQTTFTMSLLGTKEKMQKIPITLGKGIASNKTYSFLITLDVDIGELIMIKFKWENSAVWANVWDTVQTIIPWSTGPRHSGLVLKTIRVKAGETQQRMTFCSEN

>LIPG_homSap LIP-PLAT chr18:45342425 endothelial lipase 
YHYQMKIHVFSYKNMGEIEPTFYVTLYGTNADSQTLPLEIVERIEQNATNTFLVYTEEDLGDLLKIQLTWEGASQSWYNLWKEFRSYLSQPRNPGRELNIRRIRVKSGETQRKLTFCTEDPEN

>LPL_homSap LIP-PLAT chr8:19840862 lipoprotein lipase
FHYQVKIHFSGTESETHTNQAFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIQKIRVKAGETQKKVIFCSREKVSHLQKGKAPAVFVKC

>PNLIP_homSap LIP-PLAT chr10:118295418 pancreatic lipase
WRYKVSVTLSGKKVTGHILVSLFGNKGNSKQYEIFKGTLKPDSTHSNEFDSDVDVGDLQMVKFIWYNNVINPTLPRVGASKIIVETNVGKQFNFCSPETVREEVLLTLTPC

>PNLIPRP1_homSap LIP-PLAT chr10:118340480 pancreatic lipase-related 1
WRYGVSITLSGRTATGQIKVALFGNKGNTHQYSIFRGILKPGSTHSYEFDAKLDVGTIEKVKFLWNNNVINPTLPKVGATKITVQKGEEKTVYNFCSEDTVREDTLLTLTPC

>PNLIPRP2_homSap LIP-PLAT chr10:118370455 pancreatic lipase-related 2
WRYKVSVTLSGKEKVNGYIRIALYGSNENSKQYEIFKGSLKPDASHTCAIDVDFNVGKIQKVKFLWNKRGINLSEPKLGASQITVQSGEDGTEYNFCSSDTVEENVLQSLYPC

>PNLIPRP3_homSap LIP-PLAT chr10:118177414 pancreatic lipase-related protein 3  chr16:70520943
WRHKLSVKLSGSEVTQGTVFLRVGGAVRKTGEFAIVSGKLEPGMTYTKLIDADVNVGNITSVQFIWKKHLFEDSQNKLGAEMVINTSGKYGYKSTFCSQDIMGPNILQNLKPC

>PLAT_cloPer Clostridium perfringens phospholipase toxin DQ183948
KELVAYISTSGEKDAGTDDYMYFGIKTKDGKTQEWEMDNPGNDFMTGSKDTYTFKLKDENLKIDDIQNMWIRKRKYTAFPDAYKPENIKVIANGKVVVDKDINEWISGNSTYNIK

>ALOX_8R_pleHom Plexaura homomalla (coral) 8R-Lipoxygenase LOX-8R beta calcium membrane
AIYNVEVETGDREHAGTDATITIRITGAKGRTDYLKLDKWFHNDFEAGSKEQYTVQGFDVGDIQLIELHSDGGGYWSGDPDWFVNRVIIISSTQDRVYSFPCFRWVIKDMVLFPGEA

>LOXHD1_galGal_PLAT:01
KVYEVVTVTGDVRGAGTDANVFVTLFGEFGITPKTHLTSKSSTAFERSKTDVFRVKTNNVGQIKKIRIEHDNTGLNAGWFLDRVIVTDMNRPhLRFYFPCNNWLSKEDGDGLYVRDLI

>LOXHD1_galGal_PLAT:02
NKYVVRVFTGEVSGSGTDADVFINIFGEKGDTGVRKLDNDKDNFEKGAEDKFTLDAPNLGRLRKINIGHNNKGGSAGWFLAKVIIEDIGNKCVYQFPVGRWFALDEDDGKIQRDIL

>LOXHD1_galGal_PLAT:03
IVYNVAVVTGDIRGAGTNSKIHVILHGSKglKNSGTIFLEGGEFERARTDLFNVEIASLLSPLSRVTIGHDNCGVSSGWYCEKVVVYCPFTGIEQTFPCGKWLDEDEGDGLIERELY

>LOXHD1_galGal_PLAT:04
NPWSLWIWTSDIKNAGTDATIFFQIYGDKGKSDEMKLDNNSDNFEAGQTDKFMIELPDLGTFYKLRIWHEKRNPFAGWHLDKVTLLKTLTKDKYSFNCGRWLDINEDDNEIVRELP

>LOXHD1_galGal_PLAT:05
IKYRVTVCTGMVSGSGTDANVFVCLIGDQGDTGDRVLYKCinNVNKFEKGNADEFFVEAVTLKQVRRVRIGHDGKGGSSGWYLAKVIVREEGQPesEAVEFPCYRWLDKNEDDGQIVRELV

>LOXHD1_galGal_PLAT:06
VSYHISVKTGDIPGASSDSKVFIKLYGEKADTSKETLLVSdndLGNYFERGRVDEFTIDTMDIGKINRILIGHDNVGLRSGWFLASVQITVPVQGRQYMFPCNRWLDKDEADGRVEVEVY

>LOXHD1_galGal_PLAT:07
INYEVSVVTGDVRAAGTNAKVFMQIYGETGKTELIILENRSNNFERGATDIFEVEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKmdetdkkkkkkkkkseeeeeeeetkveevmDVYTFVAHRWLAKDEGDKELVVELV

>LOXHD1_galGal_PLAT:08
NTYEVHVLTGSVWGSGTDANVFLSIYGIErGDTGERQLKRSnNLNKFEKGQVDVFTIKAIDLGELKKLRIRHDNSGSSPSWFLERVEIVDLKESTTYYFPCQRWLAVEEDDGQIVRELV

>LOXHD1_galGal_PLAT:09
TTYIVKVKTGDKKNAGTDANVFITLYGSKDDTGIVSLKASklNKNKFERGKIDEFTVESVDIGDLKKIKIGHDNAGNSNGWFLEWVEIDAPSLGQCLKFPCGRWLDKSEDDGAIERFIF

>LOXHD1_galGal_PLAT:10
VPYEITVYTSDIFGAGTDADVFIVLYGSDgicTQQKSLCLNKReQRMYFERNSVNQFIVELEDVGDIIEKIRIGHNGGGLNSGWHLDRVAIRRLLPNgkgsETITFPCERWLAKSEDDGEIIRELV

>LOXHD1_galGal_PLAT:12
IPYHITVTTGTEYDSSTDSRVFIIIMGPQkVRTERLWLDLPeGKDEFADGSVEKFSVWGLDVGEIKKVEVGHDGATPESCWLMEELTIVVPTKGVMYNFVCKCWLARDKGDGLTSRILN

>LOXHD1_galGal_PLAT:13
ILYEVTVVTGDIESGGTDAGIFMTVFGSNGNTEEMQLDKNGDRFERGQEDSFIMEIADIAPLRKMRIRTDAKGTRPDWFLERIVMRNLTNQEVATFTYGDWLSKVKNAKGSLVCEM

>LOXHD1_galGal_PLAT:14
TTYTIQVKTSDIGGAGTDANVSLILFGENGDSGTLALKESnKSNKFERNQMDEFNFPNMLSLGDLCKVRIWHDNKAY

>LOXHD1_galGal_PLAT:15
KAYEIVTVTSNREDAETKENIWIILEGKLGRSKEFLMENSskKRRFERRGSTDTFQFSSKNLGDIAAICVGHCPKDgkkssakADVYWHVKEIIITEMELCNKYFFRCNGKIPLRYKRRDYKVFEC

>LOXHD1_galGal_PLAT:16
VKYETIVVTGFEKGAGTDANVFITIFGLNGDSGKRALKQKFRNLFERGKTNRFYLETLD
MGELKKVRIEHDNSGLAPGWLVERVEITNSATGVTTIFPCGKWLDENRGDGLTWRELF

>LOXHD1_schMan_PLAT:01 Schistosoma mansoni (flatworm) Bilatera; Platyhelminthes; Trematoda XP_002576380 from contig NS_000200
TLYKVVLTTADVPGAGTSAQIYITLKGEWGSSTRQKLRKEKVPTRNLRFYFYPGSTNTFSVVSPDLGGLHSVFIEHDSLRKSDSWLLESVQVFHPLTKKRYMFMCNHWFSLYKEDGLIARELF

>LOXHD1_schMan_PLAT:02
TKYSIVTVTGDQEGSGTNSKVYITIYGRTGITPRIELSQENKSTGKDILCAPFGRGTSTKFIVKAPNVGAITNIRIKQDESGNEPHWFLERVVVTDMSYPQWTYYFHLSCWLSSKYGDGKSCR

>LOXHD1_schMan_PLAT:03
TEYKLTFYTSDQKDAGTTGEVYVKLYGEKDSSREIWVNSINQKNRRQPTSYHFTRGSTVEVYLPPCPQLGEITKLKVGHNRAGSSPSWFLNKVIVDDLRMNRVFEFPCYAWITK

>LOXHD1_schMan_PLAT:04
IPLEIRLYTGDVPNAGTTAKVYLHQKTTSENKEDVYTTPYIWLEDGNYDRNGVTLFSIDLPVPKFISPLSQLVIGHDNTGHSPSWFFDKVQIYCPLNGVEQTFLYRKWLTSSKPGMKVEQILCEE

>LOXHD1_schMan_PLAT:05
IPWEISVKTSPIANSYVTAAVSIIIFGSKDKTMKIQLDRSNLEVSSEWTKVSGNEVVEMFRPNVESKFRIYIKDIGIPCKLRIQHDNKGSNPNWHLQEIVLTNLRTHEQYEFYCNRWLSTREDDGSILREIPAK

>LOXHD1_schMan_PLAT:06
YIIQIFTGNKPNSGTNANIFINIFGEKGDCGERWLGRSVNRNSELFQQNQMDEFVIEAVQLGSINKICIGHEERSPGYGWYLAKIVLTIKENPKYKLTFECYRWFDVGEDDGQIVRELFA

>LOXHD1_schMan_PLAT:07
IAYNVTVLTGTCRNAGTVANVFVHLYGLQGESKDMQLKHKETEITKFEAGKSEEFILACGKLGEIKKIKIWHDSIAPHSGWFLDEVVVIDYFLGRRYVFHVNRWLAKNEADGLISLDLQPT

>LOXHD1_schMan_PLAT:08
SYEVIVKTGGRKYAGTDSHVYITMFGINSESKEYHLANSKTHNNKFEQNHEDLFNLNAVGLGSLKKIRVRHTNTGIAPGWFLDYILIRESIEQKKMEYFFPCYQWLSATRLDGLVIREL

>LOXHD1_schMan_PLAT:09
TIYHVRIHTGSQSNISSDANVQIQLYGDKDFTGNIRLYKAYYGKEDILVNKFQAGQIANFIVKAINIGNIKKIRIEHDTAVGSARWFVERVEVEARKLGLLWKFECNR

>LOXHD1_schMan_PLAT:10
TNYQIKTFTSDISGAETTSSVYIQLYGNDSLPSSIRRLHQNNDSEQRFQRNKIDTFYVELEELQEPFSKLRIWHNDKGSSTDWHLNKVEIRKIKTNQYVFVTYIFPCNKWLSRNMDQAALERELIPS

>LOXHD1_schMan_PLAT:11
NTYEVRITTGDKAYAGTDASVYITLFGENGDSGERKLTKSLTHRNKFERGQTDVFQLEIVDLGKINKVRIRHDNSGVNPSWYLSTIEVFNISKSQSVHGLKDQPNETHHLVKYIFNCEAWLSTEHDEKVLDR

>LOXHD1_schMan_PLAT:12
IPYLITVITGSDRKAGTPGPVWISCVDKDKMNSEKFILCDCYNRTMLKRGTTRYFRFAGVKLNDLTEIQVGNDAPESPSMGWYIQSLYLSFPTIGKMYLFDCKEWLSTNRGNKK

>LOXHD1_schMan_PLAT:13
ITYHLKITTANVKRAGTDCSINLQIFGTNGVTNCYILEKTSNRFAQGITDNISLEMEDVGKLLKMRIGHDNQGKNKHWNLSCVEVTVANTNQLYRFVYDDWLSLTYGKRKSLWADLPAM

>LOXHD1_schMan_PLAT:14
TCLDIFVKTGNMPASSTDANVYVQLFGEYGDSGEILLKQTVSNQKPFQNNSIDHFKIPSILKLGNLARCRIWHDNKGSSPNWYCEWLEVKEVLIPGEKNLACNWKFAFNKWLSVSDDNKQLLRDAPCS

>LOXHD1_schMan_PLAT:15
VYEVVIETGNLKDSGTTCDAWIILEGKHGRSPKLELVNQVGNPILQINQMNTFQLPSFPLGDLETIRLGIQERNINKQTNPNDIQSQKWFCEKVSIKDPVSKRTYIFTIHQWLS

>LOXHD1_schMan_PLAT:16
VMYKVSIYTGTKGCANTDANIFITMFSTTPGLNSGRIALKRENNNLFDRKQLDEFYVESIDLESIQRIIIEHDNTGVSPDWYLDKVLITNQTNNQIHLFQCYQWISKKKGDCRLWKELLVS
 
>LOXHD1_triAdh_PLAT:01 
VAYQFGVKTGDKKGSDTDAVYIQVIGTKDKIPKKRLFKKQETEKTERGNLFKFDKSTVEKFAVQHRDIGDPVKLIVEHDGNEKRHGWFLEEITLTNIQSKKSWLFPCHKWLSKYEGDRKLCYE LKPLAKAGK

>LOXHD1_triAdh_PLAT:02 
AVYEVSVLTGDKRGAGTDANVSVTLFGKHTSSPKIQLLKSSKHKNPFERNNTDEFKIRTRDVGKLSKIRIEHDNAGFGPGWFLDKVIICNLEKPNVKYYCPCNQWLAKDVGDKSISRD LTAYTDPNAAPSA

>LOXHD1_triAdh_PLAT:03 
YVYIVHTFTGNKRGAGTDANVYAVIFGDSGDTGEKRLDNSKNNFEKSRKDTFKLSCSCVGKLERLRIRHDNTGLFAGWYLDKVVVEDPQEQQSYTFYCRRWLSKTEDDGEICRDLI VSASGDDGDDSVAPKG

>LOXHD1_triAdh_PLAT:04 
YPYHIHVTTSDVKNAGTDAEVYVVMHGEGKKSKELNSGKLVLANSEKKKNTFERAMTDIFHMECAEMLSPLTKLTVGHDNKGLAAGWHLDRaIVIDCPTTGIEQTFLCQQWLDRKAGDGLTERELVEA FDMRKTRRPK

>LOXHD1_triAdh_PLAT:05 
QLWFAWIWTSDIRGAGTDANVSMQIYGDKGKSQEIKLGNNTDNFEQATLDKFKLEIDQVGVPYKLRIGHDNSNAFPGWHLDKVKLENMNDKEQYLFNCNRWLSRSEEDNEIIRELPAS GPNCPNYPI

>LOXHD1_triAdh_PLAT:06 
VIYEVSVHTGNKMGGGTDANVFIKIYGELGDSGYRPLKSSKSHNNKFERNQVDVFHIEAVTLKALKKIKIGHDGNNPGAGWFLDKVVIKELNGEASNEFPCNRWLSKSEDDGQIVRELFLK SDTPLLKT

>LOXHD1_triAdh_PLAT:07 
TSYHISVKTGDVRNAGTDANVFIQIFGAKDDTGRVRLKQSLNTSNKFERNRIDKFIIEAAQIGKIEKIIIGHDGKGLGSGWFLDYIELDVPSVGRLYRFSCHQWFDSTEGDRKVERELYPS ECIKSAAK

>LOXHD1_triAdh_PLAT:08 
IPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFKVECEDVGKLRKLRIGHDSAGMGSAWFLDKVYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEIS PVGVDGALAE

>LOXHD1_triAdh_PLAT:09 
MTYTIRVITGNKFGCGTNANVFINMYGEEGDSGERQLKKSETHTDKFERNQEDVFKISCLSLGELKKIKIRHDNSGFRPAWFLDKVIIEVGESKYQFMCDRWLAKDEDDGQISRELLPQ SDEQSRAEAIGASKDLQKKVAS

>LOXHD1_triAdh_PLAT:10 
TTYNVSVTTGDIKGAGTDANVHIVLYGEKDDTGLIHLKNSTTHSNKFERNQEDRFVVEAIDIGELKKIKIGHDNKGGMAGWFLNKVEIDIPSLGRRLLFPCGRWIDKGKDDGALER ELYPLNEAEETYRPH

>LOXHD1_triAdh_PLAT:11 
IPYEVTVYTTDKRGASTGANVYVVIYGEENQTEQASLEPDKKRRKQYFKNGAIDKFVLELDDVGEEITKLRIGHDGKGWGAGWHLDKVEICRLLDGGKASKKFTFQCNRWLASDEDDGAIVRELVPS EIVEKSSKDGGQVKTKVTKPTDGLKV

>LOXHD1_triAdh_PLAT:12 
KPYTIHVFTGDVDGAGTNANVFLTIFGESGDSGERKLAKSDTHYDKFERNQEDIFHIEAADLGRLFKVKIRHDNTGSLFSPAWFLNRIEIVDDENEETTAFPCERWLAKKKDDGKIDRTLFVK 

>LOXHD1_triAdh_PLAT:13 
VPYNIKVTVGEESSKNFQETLHLELFGQIEEEKSGPIELSPEKKSDKTFYPGKITTFYVSAAEVNIIEKIQVSHNSYMPDSGIYLKEIEVDVPTIGNKYIFPCNRWLAKDKDDSKTSRIFTAA 

>LOXHD1_triAdh_PLAT:14 
KPYELTIHTGDVQNAGTDSNIFVILFGTKGRTPEISLEKNEDRFERAKVDIIPLELDDVGTIKKIRIGHDGKGSRTDWYLEKASIQRMDTLDMYMFRANQWFSKKIDDKKLVREI PAETSKEGATTIKK

>LOXHD1_triAdh_PLAT:15 
INYVLSTHTSDKRGSGTDANVFVIIFGENGDSGEIALKKSETNWNKFEKGQTDVFLINDRLSLGRLQKLRIWHDNAGFGASWHLASVDIVDESTGVKYTFPCDKWLSKSNGDKLILREL PCAETAGNTAASKATKQESKSGK

>LOXHD1_triAdh_PLAT:16
AEYEIAFTTGTEKRAGTNQDVAIVLKGKSEKSREFLIENNEDKKYFSKGKTNKFTYTCKPLGDITKAIVSHRESAIGEEPDSKNSSWYLKVVTVVHKASGTTYKFPCNKWIDLDDDEENNSSVTLKC KSADVAASSKAKPVELKP

>LOXHD1_triAdh_PLAT:17
VKYEVTVVTGDEKGAGTDANVSVILYGDNGDTGPRPLKKKFVNLFERNQHDKFTIEALDLGKLTKLHIEHDNKGWGASWLLDRVEVHNVDSNETIIFPCKQWLDKKKGDGQIAKDLLPES* 

>LOXHD1_monBre_PLAT:01 Monosiga brevicollis (monosiga)
GHASLEIFTSKRSNPVSKSEKYITVVGTKGRSDAIQLAAPGVHFRAGNKDVFQVNLTGIGKPTKVILENTGTKRTDGWCVSKVVLVKKTDKGTRRYRFSGPVWLSKHHDEMKLKR

>LOXHD1_monBre_PLAT:02 Monosiga brevicollis (monosiga)
NGYRIDCYTGDVANAGTDAVATIQLFGSKGQSPMVELRRSDGQAFQRARVATFTLDDLANLGKLKKLVISHNGHGMASGWFLDKIIVTSLSSNKATVFPCDAWLDRKNGRSKELVAR

>LOXHD1_monBre_PLAT:03 Monosiga brevicollis (monosiga)
TTFTIRVMTGDRRGAGTDANVQCTLFGEDGESGPHTLNTSRNDFRRGHTDVFAVSSRKIGTLKRLRIWHDNGGAGPAWFLDAVEVVDEASGQTYRFECNRWLAKDEDDGQISRELTCN

>LOXHD1_monBre_PLAT:04 Monosiga brevicollis (monosiga)
KSYKLTIFTGDKRNAGTSANVFCKLVGERGASDNVILENSSKNFQRDRTDIFTVEASDLGSLRHIVLGHDNHGMGAGWYVERFSLEVPSEGKLYNVDVKQWFATDMSDGAIERTFRLD

>LOXHD1_monBre_PLAT:05 Monosiga brevicollis (monosiga)
LDWKCTIYTSDVANAGTDANVFMQVYGKKGKTDVVPLKNKSDTFERGQTDELRVQLINVGSLRKLRVWHDNKGMASGWHLDRIVLSRDGEEYIFPCAEWLAVSEGDKEIVRELPAT

>LOXHD1_monBre_PLAT:06 Monosiga brevicollis (monosiga)
VEYTVRVATGHARFAGTNADVFVMLTGELGDSGKRALLRSQTNRNKFERGKEDVFTVAAVDLGKLTSVTVGHNNAGTSAGWFLDKIVVLDPRRGEEEEFPCHRWLAVDADDGQIERELVPK

>LOXHD1_monBre_PLAT:07 Monosiga brevicollis (monosiga)
TTYIVKIKTGDVRHAGTDANVFVQLFGKTGESTQLKLRNSETYSDAFERNKMDIFKFELLDLGDLSRILVGHDNKGMGAAWFLDYVEVEVPSIRTRWKFPCSRWFSKSQDDGLTER

>LOXHD1_monBre_PLAT:08 Monosiga brevicollis (monosiga)
APYLFRFYTSDVAFAGTDANVSVVLYGDEGKTEELVVNNQSDNFERGKADDFKLACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVEL

>LOXHD1_monBre_PLAT:09 Monosiga brevicollis (monosiga)
RTYRVKVHTGDQKGAGTDANVYVNLHGSLGDSGDRHLKNSLTHTNKFQRKTVDEFDIDAVTLGDINKVKVWHDNAGLGAAWYLEKIEVVDTADDKTYIFPCAQWFAKSMGDGQIAREL

>LOXHD1_monBre_PLAT:10 Monosiga brevicollis (monosiga)
FKYRISVHTSDVKHAGTDANVDIVLYGEKGDTGKIRLAKSETHRDMWERGNCDVFTVSAIELGDLKRVDIMHDGKGVGSGWHLNKVVVDAPQAGKTWTFMCDAWLDKATDDGTMAK

>LOXHD1_monBre_PLAT:11 Monosiga brevicollis (monosiga)
VPYEIIIKTSDVRNAGTDANVFIDLYGRDQEERDLTAHHEFKDAVKAHFERNLEDRFNVELPDVGSIYKIRLGHDGKGMSSSWHVASVVVINQRTHERFEFPCDAWLSKDKDDKKLVREFAVG

>LOXHD1_monBre_PLAT:12 Monosiga brevicollis (monosiga)
AIYKIHVFTGDIKHAGTDANIYVQIFGDTGDSGEIKLEKSETYRDKFERGHEDIFTHRCLDLGPLRKIKVRSDGKGLMGGDWYLDRVEVHQENDLSEPPVRFVCQDWFKRGKQEGDTLEREITAQ

>LOXHD1_monBre_PLAT:13 Monosiga brevicollis (monosiga)
LEYKVTVYTGTDTQAGTTANVWLQLFGEKDAPLTPAPPSPSKLSRSGSLFGRRRRASSDAQSVSSSLSAGASGPRETSTGRLQLNNAPADLQSGAKTTFTVTGLDVGELVGLEIGHDDERDKWYLEQVVVEVPKSATHAARRYEFKAGVWLAARADGSTSGSAK

>LOXHD1_monBre_PLAT:14 Monosiga brevicollis (monosiga)
LEYTLKVYTASADGAGCTAVPQVQLFGDKHTTEALPLRAGGDILPASVVETQHRVPDLGALLKVRLMVPRGSSWTVEKVEFGRAGQTPITFVGSDGSAVTLGAERLS

>LOXHD1_monBre_PLAT:15 Monosiga brevicollis (monosiga)
TSYRVYVTTADERGTGTDANVSIILYGAMGDSGEHSLTKSETFDDPFERGNTDVFTLEVPDLGELQRARIWHDGKGMFSSWKLDKIVVVVEATQSRYELPCGQWLSKNKGDKQLTRDLAVASKR

>LOXHD1_monBre_PLAT:16 Monosiga brevicollis (monosiga)
GTYKLEVATDSRAGGGCKGPVRIMLLDAEKNQLPLTLEPPGGEFAPGSVEHLVFDNVMLLGPLTELRIRRKPSGASSRRGAEDDDEDDNEASGASSQSGSAVSPWHLEHIIVKHLQSGQSFVFKGPSKGLSRSRAKLSVHTEA

>LOXHD1_monBre_PLAT:17 Monosiga brevicollis (monosiga)
AQYEVAVTTGTERGAGTDSNVFVTLFGKNGDSGERALAKSKTFRNMFESGNTDVFDVECQDLGELTKIEVKSDLKGFGAAWQLDKIKVTRTGSQNSWQFKCDQWFDKKQGAEHTFSVA

Reference PLAT:07 domains

>PLAT:07_homSap Homo sapiens (human)
2 LVHYEVEIWTGDVGGAGTSARVYMQIYGEKGKTEVLFLSSRSKVFERASKDTFQ 0
0 LEAADVGEVYKLRLGHTGEGFGPSWFVDTVWLRHLVVREVDLTPEEEARKKKEKDKLRQLLKKERLKAKLQRKKKKRKGSDEEDEGEEEESSSSEESSSEEEEMEEEEEEEE   FGPGMQEVIEQHKFEAHRWLARGKEDNELVVELVPAGKPGPE 1

>PLAT:07_monDom Monodelphis domestica (opossum)
2 LIHYEVEIVTGDMGNASTSARVYMQIYGEEGKTEVLFLKSRSKVFQRGNTDTFQ 0
0 LQEAEVTPEEEARKKKEMDKLRQLMRKERLKAKEEQKRKRKLAKGSDVEDEEESSSEESSEESEEETEIEEEDEE                                           FQEVVDVYRFHAGRWLATDEEDKDLDMELAPSGRSGPQR 1

>PLAT:07_ornAna Ornithorhynchus anatinus (platypus)
2 LIHYEVEIVTGDMGYAGTNARVYMQIYGELGKTEVLHLTSRTNVFEQGATDTFQ 0
0 LEATDVGEIYKVRLGHSGEGFGSGWFIESLVLKRLVLKEVEPNPEEEKRKAKERERAREQRRKERLKAKQQRKKKKKMKKSSDDEDSEAEDSEEEEGSSEEESSSSSSEEEVEEEFGPGIKEVIDVYKFEAHRWLARDEDDKELIVELEPANRPGPE 1

>PLAT:07_galGal Gallus gallus (chicken)
2 LINYEVSVVTGDVRAAGTNAKVFMQIYGETGKTELIILENRSNNFERGATDIFE 0
0 VEAADVGKIYKIRIGHDGKGIGDGWFLESVTLKRLATKMDETDKKKKKKKKKSEEEEEEEETKVEEVMDVYTFVAHRWLAKDEGDKELVVELVPDGESELE 1

>PLAT:07_taeGut Taeniopygia guttata (finch)
2 LINYEVSVVTGDVRAAGTNAKVFMQIYGETGKTELIILENRSNNFERGATDIFK 0
0 REAADVGKIYKIRIGHDGTGIGDGWFLESVTLKRLATKTEGSDKKKKKKKKSEEEETKEEEGMDVYTFVAHRWLAKDEGDKELVVELVPDGESDLE 1

>PLAT:07_anoCar Anolis carolinensis (lizard)
2 LINYEVCVATGDVRNAGTNANVFMQIYGELGKTELLILKNRSNNYERGASETFR 0
0 VEAVDVGKVYKIRIGHDGKGFGDGWFLDSVVVKKLPTKVPKKKKKKKKKKTPEEEEAEEGPGIMEVYNFTPCRWLASDEEDKELVVELVPDEGSELE 1

>PLAT:07_oryLat Oryzias latipes (medaka)
2 VINYEIAVVTGDVRAGGTNASVFCQIYGEEGKTEVLNLKSRSNNFERGTTEIFK 0
0 IEALDVGKIYKIRIYHDGSGIGDGWFLETVDIKRLTMALVQVEVKKEEAPKKDKKKDKKKKKKEEEEVEIIEEMQEVVETFTFTCNRWLARDEEDGEIVVELLTEENEDLE 1

>PLAT:07_gasAcu Gasterosteus  aculeatus (stickleback)
2 VINYEVTVVTGDVTFAGTNARVIIQIYGDKGKTEVIILESRSNNYERNTTEIFK 0
0 IEAKDVGKIFKIRIGHDGSGIGSGWFLETVDVKRLILALVPKEKKKEDKKKKKKKKEDVDEEGGEEMQEVVLTYSFPCSRWLAGGEEDGELVVELLPDDAKELE 1

>PLAT:07_takRub Takifugu rubripes (fugu)
2 VINYEVTVVTGDVTFAGTNAKVFVQIYGDKGKTEVIMLESRSNNYERNAMEIFK 0
0 IEAKDVGKIFKIRIGHDGLGIGSGWFLEKVYVKHLIMALVPRENKKDDKKKKKKKKKDKEDEEEVGGEEMQEVVVTYHFPCSRWLASGEDDDDLVVELLPEDAEELE 1

>PLAT:07_petMar Petromyzon marinus (lamprey)
2 GINYQVSVHTGNVRSAGTNANVFIQLYGDMGKTEVHNLRNRSDNFERASNDIFK 0
0 VEAMDVGKVVKLRVGHDNSGMGSGWFLDSIVIRRLRQSSPHRPQPVDAEEDEDEEDDEEAEDEDSEEVQTYTFPCKRWLARDEDDGEIVRELLPQDCAEME 1

>PLAT:07_sacKow Saccoglossus kowalevskii (acornworm) Bilateria|Deuterostomia|Hemichordata
2 GIPYEITVITGDKSGAGTDAQVFIRMYGLKGKTDEFILNNRTDNFERGMTDKFK 0
0 IEAADVAMLTKIRIGHDNSGRSAGWYLERVIIERFPPKRKMKRKRSGTPRRRGEYDEEDYDDIPETNVVNFVCNRWFAKDEEDHQIVRELLPTDEEALKGH 1

>PLAT:07_strPur Strongylocentrotus purpuratus (sea_urchin) 
2 GIPYEITVITGDKSGAGTDANVFLTMYGDDGAKTEEFSLRNRTDNFEKNMTDKFK 0

>PLAT:07_triAdh Trichoplax adhaerens (placozoan) Eukaryota|Metazoa|Placozoa 
2 KIPYQISVHTGDIRHAGTDSNVFAVIYGENGKTEELKLRNKSDNFERGQVDVFK 0
0 VECEDVGKLRKLRIGHDSAGMGSAWFLDK 00 VYVRRLPPKSGKKSKETDEREEETAKKDADEPEKLDENNYLFVANRWLSKEEGDRQTVIEISPVGVDGALA 1

>PLAT:07_monBre Monosiga brevicollis (choanoflagellate) Eukaryota|Choanoflagellida 
2 PMEEDVSAPYLFRFYTSDVAFAGTDANVSVVLYGDEGKTEELVVNNQSDNFERGKADDFK 0
0 LACKPVGRPSKIRLSAHGGGMSADWHLEKIEVHELGQARIYTFEHNDWLRKGTKAKPFMVELPLRRIETVDDNGREVVEELALDANKRTYR 1

See also: Usher: USH2A | Usher: CDH23 | RBP3 (IRBP) | RPE65 | Transducins

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