Opsin evolution: RGR phyloSNPs: Difference between revisions

Latest revision as of 21:33, 22 November 2010

Introduction to RGR Opsin Evolution

A Curated Set of 54 RGR Opsins

The collection of RGR opsin reference sequences is greatly expanded below to 54 species of vertebrates from the more limited yet phylogenetically representative set found in the opsin classifier. This expanded set brings much needed branch length to detailed studies of evolutionary change such as reduced alphabets at given residues, phyloSNPs, alternative splice forms, and gene loss in marsupials.

It has not proven possible to date to find an ortholog of RGR in any species diverging prior to lamprey (other than perhaps tunicate). tBlastn searches of the new amphioxus genome yields nothing, as does blastn searches of the trace archives. Similarly, no closely related homologs can be found in earlier deuterostomes and protostomes, even though neuropsins and peropsins are readily traced back further. Since RGR is an ancient gene family (based on intronation and weak blastp matches) -- rather than derived in Bilateran times from a nearest paralog -- RGR genes must have been retained along the stem but not in most terminal leaves.

Comparative genomics of RGR at E/DRY

The comparative genomics of RGR illustrates the danger of generalizing from phylogenetic under-sampling (just studying humans and mice): with deeper sampling of 56 species, it emerges that the E/DRY motif -- conserved across all classes of opsins (including generic GPCR) and critical to maintaining non-signaling state -- has become GRY in all boreoeutheran mammals (it's ERY in afrotheres and xenarthrans and DRY from platypus back to shark and even tunicate divergence, and DRY consistently in neuropsins and peropsins).

In other words, after several trillion years of branch length conservation as charged amino acid, a radical amino acid substitution has taken hold in laurasiatheres and euarchontoglires -- to a glycine with its minimal inert side chain. And in this subclade of placental mammals, this glycine has been conserved without exception for over two billion years of branch length, not consistent with gain of a different selective pressure.

Given the importance of this motif for maintaining the non-signaling state, this suggests a major change in functional properties of RGR opsins within boreoeutheres. Yet there are no obvious differences in ciliary opsin imaging vision between or retinal pigment epithelia of elephants and humans. And how does 11-cis-retinal replenishment work in marsupial? (Opossum genome has lost due to a chromosomal rearrangement; the gene is also absent from wallaby assembly and brushtail transcripts.) No obvious change took place in cone or rod opsins either at the transition form D to E to G.

We might ask whether any correlated residue change took place in another residue, either adjacent in the linear sequence or adjacent after the 3D structure is considered. To do this, the phylogenetic depth must be increased to the maximum possible today (50 vertebrate genomes) and every residue scored for clade-congruent changes.

It emerges that no contemporaneous coevolutionary changes accompanied the D to G transition. The bulk of such changes occurred on the 75 myr stem between the platypus divergence node and placental node. These cannot be further resolved because marsupials lost RGR. The other cluster of clade-coherent events occurs on the stem dividing ray-finned fish and tetrapods. (Here fish are not assumed primitive -- they simply share the ancestral value with earlier diverging cartilaginous fish.)

RGR_homSap  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_panTro  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_gorGor  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_ponPyg  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_nomLeu  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_macMul  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_papHam  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_calJac  RWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCT  
RGR_tarSyr  RWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCT  
RGR_otoGar  RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT  
RGR_micMur  RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT  
RGR_tupBel  RWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCT  
RGR_musMus  RWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCT  
RGR_ratNor  RWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCT  
RGR_cavPor  HWP-GSGHCQALGFQGFTTALASISGTAALSWGRHQQCCT  
RGR_dipOrd  HWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCT  
RGR_speTri  RWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCT  
RGR_oryCun  RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT  
RGR_ochPri  RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT  
RGR_bosTau  RWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCT  
RGR_susScr  RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT  
RGR_turTru  RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_equCab  RWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT  
RGR_felCat  RWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCS  
RGR_eriEur  RWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCT  
RGR_myoLuc  RWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCT  
RGR_pteVam  RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT  
RGR_canFam  RWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCT  
RGR_sorAra  RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT  
RGR_loxAfr  RWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCT  
RGR_echTel  HWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCT  
RGR_proCap  RWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCT  
RGR_dasNov  RWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCI  
RGR_choHof  RWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCT 
RGR_monDom  gene lost
RGR_macEug  gene lost 
RGR_ornAna  HWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCS  
RGR_anoCar  YWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCT  
RGR_galGal  YWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCT  
RGR_taeGut  YWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCT  
RGR_xenTro  YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT  
RGR_xenLae  YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT  
RGR_danRer  YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT  
RGR_pimPro  YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT
RGR_takRub  YWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT  
RGR_tetNig  YWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT  
RGR_gasAcu  YWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCT  
RGR_oryLat  YWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCT  
RGR_gadMor  YWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCT  
RGR_poeRet  YWPFGQEGCNYHAFQGMISVLASISFMAAIAWDRYHQYCT  
RGR_osmMor  YWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCT  
RGR_spaAur  yWPYGSDGCQTHGFQGFCTALASIHFIAAIAWDRYHQYCT
RGR_hipHip  YWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCT
RGR_melAur  yWPFGQDGCAYHGFQGMISILASISFLAAIAWDRYHQYCT
RGR_calMil  YWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCS

PhyloSNPs in RGR

All significant phylogenetic information for RGR -- SNPs that stuck in all descendent clades -- can be extracted with simple cladesheet methods (described shortly). This involves disentangling sporadic non-adaptive variants from neutral flop-flopping within a reduced alphabet from clade-coherent change. Clade-coherent change is what makes a boreoeuthere a boreoeuthere (or a whatever a whatever).

PhyloSNPs are residues fixed for considerable branch length that subsequently experience an enduring change on one descendant branch while maintaining the ancestral value in all other descendant species. Because billions of years of branch length are involved (given the current 50 vertebrate genomes available), this change has to have been and continue to be functionally adaptive. Collectively, the set of phyloSNPs on a given internode stem defines at the protein level what is distinctive about the clade and common to it.

The array at left is time-sorted horizontally (with sub-sorting for noise) and phylo-ordered vertically as indicated by the coloring. Dots mean the amino acid residue in the indicated species agrees with homSap. Starting at the lower left corner, 11 positions in RGR where, at the phylogenetic depth of shark to fish, a significant change took place in the tetrapod stem prior to tetrapod divergence from lobe-finned fishes and held in tetrapod clade and its outgroups to the present day. For example V>I, G>A, P>A, M>F for the first four.

These phyloSNPs do not assume or support teleost fish proteins being more 'primitive' or more ancestral than mammal -- indeed fish in general are much more evolved from ancestral state than human, meaning a random outgroup protein from chondrichthyes will have higher percent identity to mammal. Cartilaginous fish and lamprey nodes play a key role in allocating phyloSNPs: in parsimony it suffices to have the two preceding nodes the same to establish the ancestral state on their interstem. Skate and dogfish ESTs can validate elephantshark genome; some opsin data exists for multiple species of lamprey. There will be phyloSNPs that just make fish fish but that is not the focus here.

Looking at the lower middle, at 14 positions after the phylogenetic run of shark to platypus, a significant change took place in the theran stem and held in both sister clades to the present day. For example M>L, F>L, F>L, K>P for the first four. In the lower right, at 1 position in RGR where, at the phylogenetic depth of shark to Afrothere + Xenarthra, a significant change took place in the boreoeutheran stem and held in the descendent clade and outgroups to the present day, E/D>G. As RGR is a GPCR signaling protein and the E/DRY motif (which helps prevent false signaling) has been conserved for many trillions of years of branch length. This is an example of an interpretable clade-coherent functional change making a boreoeuthere distinct from Afrotheres, Xenarthra, and everything else.

Colors group residues nearby in the linear sequence that changed at about the same geological time. These are candidates for co-evolving residues where after the first changes, a second makes a compensatory shift. The interactions of residues in different transmembrane helices that touch are another form of adjacency. These are not yet displayed but likely will suggest further co-evolving candidate pairs.

Some phyloSNP positions exhibit more background sporadic variation than others. These can be filtered to only the most pristine cases for purposes of additional bioinformatics or experimental investment. Doubling the number of species with sequenced genomes would have the effect of further refining these distinctions.

RGR has an unusual high proportion of phyloSNPS at 32 out of 292 residues. Proteins such as PRNP, of the same length but twice the sequence density and more rapidly evolving, appear not to have a single phyloSnp of depth beyond euarchontoglires.

Loss of RGR in marsupials

Notably absent are RGR genes in marsupials; for other genes, marsupial representatives are typically available from 2-3 species. By locating syntenic genes in placental mammals and platypus, the appropriate region of the opossum genome can be identified. However the adjacent orthologs are now on separate autosomal opossum chromosomes, suggesting a translocation has disrupted the RGR genes. None of the individual exons can be found by tblastn of the genome or blastn of the very extensive trace archive coverage. This lack of even pseudogene debris supports the idea of gene loss and decay sometime fairly soon after marsupial divergence.

The loss of RGR in marsupials further challenges the usual functional explanation given to RGR in placental mammals (a complex with 11-cis-retinol dehydrogenase RDH5 that replenishes cis-retinal at cone and rod opsins). Since marsupials are known from experiment to have normal color and rod vision via ciliary opsins, either other pathways for replenishment exist or the role of RGR was different in the theran ancestor.

If RGR has 1/5th the quantum efficiency of rod rhodopsin and 1/100th its abundance, the question arises how it keeps up with bright light replenishment needs. Furthermore, knockout mice develop a normal retina and RP epithelium without any morphological phenotype (unlike those lacking trans-retinol isomerase RPE65), whereas humans even heterozygous in RGR for Ser66Arg exhibit ERG abnormalities and eventually retinitis pigmentosa and RPE degeneration.

Most experimental work has unfortunately been done on GRY species whereas platypus and earlier diverging species have the more conventional DRY or ERY, as do afrotheres and xenarthrans (implying this for the lost marsupial and stem RGR). Thus the role of RGR could have drastically shifted after elephant/sloth divergence. Marsupials lost the gene altogether while placentals retained it but by the time of boreoeutheran divergence with a rather altered signaling properties and functionalities.

Gain of RGR2 paralog in teleost fish

Zebrafish is complicated by having a second diverged copy RGR2 presumably arising from its whole genome duplication. This is less like the tetrapod RGR (51% identity vs 68% relative to chicken, 42% vs 57% relative to human). However it has far more abundant transcripts than its tetrapod-like RGR1. It also has intact signaling region DRY LAKTSPIFHAVLYAYGNEFYRGGVWQ and presumably uses the same Galpha as RGR1.

Functional partitioning is not clear because paralogs have retina/RPE transcripts; indeed RGR2 arose from a specific embryonic RPE expression profiling experiment. Those authors did not realize this was RGR2. Perhaps significantly, RGR1 did not make the list of genes with enhanced RPE expression relative to retina.

RGR2 can also be recovered from 9 species of teleost fish but has no counterpart in chondrichthyes or tetrapods, suggesting by parsimony that a single lineage-specific exon-preserving duplication occurred within fish lineage prior to their speciation (rather than arising earlier and being lost from these other lineages). This implies that RGR2 has carved out a distinct niche with selective advantage preserving it for many billions of years of branch length time.

Despite sequence identity at time of duplication, RGR1 has retained distinctly more ancestral (parental gene) character, evidently by selection that continued by retention of major ancestral functions. Fish RGR2 are evolving more rapidly among themselves than RGR1 yet may shed light on core conserved features of this opsin class:

The two paralogs do not have any indels of phylogenetic significance, though the amino terminus and less-well conserved carboxy terminus have somewhat variable length. Within the Otocephala fish (ie Danio and Pimephales), RGR2 has a 2 residue insertion PA in TM4 of obscure taxonomic interest as a rare cladistic genomic event. RGR2 like RGR1 terminates consistently in all species with basic residues, eg KQK* despite variations in last exon length. The specific function of this cytoplasmic tail motif is unknown. It is unique among all other opsin classes.

The best PDB model for RGR2 is 2ZIY from squid melanopsin MEL1_todPac but this has only 25% sequence identity and significant loop gaps. No RGR2 representatives exist at SwissProt as of Jan 08. However transmembrane sections can be reliably predicted ab initio or by homology. The sole glycosylation site NFT in the 3rd extracellular loop of RGR1 is missing in RGR2. It's not clear what that implies for GPCR processing in the ER. The predicted disulfide at 88-162 CQA-CTL is however invariant. The sole known retinitis pigmentosa mutation site in the second transmembrane helix of human RGR, S66R, is not a conserved residue in RGR2.

RGR membrane topology: extracellular transmembrane cytoplasmic
 Bold type: S66R mutation, disulfide, glycosylation, DRY and YR motifs, PA indel, Schiff lysine

>RGR_homSap               >RGR2_danRer 
MAETSALPTGFGELE           MASYPLPEGFTDF
VLAVGMVLLVEALSGLSLNTL     DMFAFGSALLVGGLLGFFLNAI
TIFSFCKTPELRTPCH          SVLAFLRVREMQTPNN
LLVLSLALADSGISLNALVAA     FFIFNLAVADLSLNINGLVAA
TSSLLRRWPYGSDGCQAH        YACYLRHWPFGSEGCQLH
GFQGFVTALASICSSAAIAW      AFQGMVSILAAISFLGAVAW
GRYHHYCTRSQLAWNSAVS       DRYHQYCTKQKMFWSTSIT
LVLFVWLSSAFWAALPLLGWG     ISCLIWILAVFWAAMPLPAIGWG
HYDYEPLGTCCTLDYSKGDRNFTS  VFDFEPLRTCCTLDYSQGDRGYIT
FLFTMSFFNFAMPLFITITS      YMLTITVLYLAFPVLVLQSS
YSLMEQKLGKSGHLQVNTTLPART  YSAIHAYFKKTHHYRFNTGLPLKA
LLLGWGPYAILYLYAVIADV      LLFCWGPYVVVCSLACFEDV
TSISPKLQ                  SVLSPRLR
MVPALIAKMVPTINAINYALG     MVLPVLAKTSPIFHAVLYAYG
NEMVCRGIWQCLSPQKREKDRTK   NEFYRGGVWQFLTGQKSADKKK

Comparative rates of evolution within paralog classes:

RGR2_gasAcu 100%    RGR1_gasAcu 100%
RGR2_tetNig  87%    RGR1_tetNig  90%
RGR2_oryLat  82%    RGR1_oryLat  87%
RGR2_pimPro  71%    RGR1_pimPro  87%
RGR2_danRer  69%    RGR1_danRer  87%

Signaling regions of RGR2:

RGR2_danRer DRY LAKTSPIFHAVLYAYGNEFYRGGVWQ
RGR2_tetNig DRY IAKTNPIFNALLYTFGNEFYRGGVWH
RGR2_gasAcu DRY VAkTNPIFNALLYSFGNEFYRGGVWF
RGR2_pimPro DRY LAKTSPIFHAAMYAYGNEFYRGGIWQ
RGR2_oryLat DRY IAKTNPFFNALLYSFGNEFYRGGVWN

Alignment of zebrafish RGR1 and RGR2:

RGR1_danRer  MVTSYPLPEGFSEFDVFSLGSCLLVEGLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLRYWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCTRTKLQWSSAITLVLFTWLFTAFWAAMPL--
RGR2_danRer  .-A........TD..M.AF..A...G.........IS.L...RV..MQ..N..FI.N..V..LSLNI.GL...YACY..H..F..E...L.A...MVSI..A.S.LG.V..........KQ.MF..TS..ISCLI.ILAV.......PA

              FGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAKFNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRMIAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKIESPAIENKSK
              I...VF.F............Q...G.IT.MLTITVLYLAFP.L.LQ...SA.HAY....HHYR..T.L...AL.......VVVCSL.CF.DVSVL..R...VL.V......I.HAVL..Y...F....V..F.....SADKKK

Alignment of all RGR sequences

Here 59 regularized vertebrate sequences are aligned. Color along top row indicates alternating extracellular, transmembrane, and intracellular domains. Color otherwise shows GRY, ERY, and DRY species (which includes all RGR2). The second alignment has extracted only the four cytoplasmic loops, all that is directly relevant to heterotrimeric Galpha protein binding. The third alignment shows cytoplasmic domains as a difference map. Then selected sequences are aligned relative to shark, with fragmentary basal lamprey included. Finally distal regions are shown.

            .................................................................*.....................s-......................GRY..............................................-s.........gly................................................................................K.....NAINY......YR..................
RGR_homSap  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTRSQLAWNSAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKREKDRTK  
RGR_panTro  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTRSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAIPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK       
RGR_gorGor  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLAPAESGISLNALVGATSTLLGRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTGSTLACKSAVSLVLSGRMSSAFWADLPLLGWGPYDYEPLRTCCTLDYSEADRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSKKDRTK       
RGR_ponPyg  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTGSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAVLYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK       
RGR_nomLeu  MAETSVLPTGFGELKLLAGGMGLLAEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTGSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAVNYALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_macMul  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTRSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_papHam  MAETSALPTGFGELEVLAVGMVLLVEALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTRSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_calJac  MAESSTLPTGFGELEVLAVGMVLLVEALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLRRWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCTGSQLAWNSAISLVLFVWLSSTFWAAFPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQVNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQMVPALIAKMVPTIDAINYALGNEMICRGIWQCLSPQKSEKDRTK       
RGR_tarSyr  MAEAGALPAGFGELEVLAVGMVLLVEALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLRRWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCTGSQLAWNTAISLVLFVWLSYAFWAALPLLGWGHYDYEPLGTCCTLEYSKGDRNFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQVNTTLPIRTLMLGWGPYALLYLCAVIADVTSISPKLQMVPALIAKTVPTINAYHYALGSEMVCRGIWQCLSPHSSEQDRAK       
RGR_otoGar  MAEPGTLPAGFGEIEVLAVGTVLLVEALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLRRWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCTGRPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYDYEPLRTCCTLDYSRGDRNFTSFLFTMAFFNFLTPLFITLTSYQLMEQKLRRSGHLQVNTTLPARTLLLGWGPYALLYLYATIADVTSISPKLQMVPALIAKTVPTINAVNYALGSEMVCRGIWQCLSLQRSKQDGAK       
RGR_micMur  MAEPGTLPTGFRELEVLAVGTVLLVEALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLRRWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCTGSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDRNVTSFLFTMAFFNFLIPLFITHTSYQLMEQKLKKSGHLQVNTTLPARTLLLGWGPYALLYLYATVADVTSISPKLQMVPALIAKTVPTINAINYALGSETVCRGIWQCLSPQRSEQDRAK       
RGR_tupBel  MAESGALPSGFGELEVLAVGTVLLVEALSGLSLNSLTVFSFCKSPELRTPSHLLVLSVALADSGISLNALIAATSSLLRRWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCTGSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDRNFTSFLFTMAFFNFLMPLFITLTSYWLMEEKLRKGGRLQVNTTLPSRTLLLGWGPYALLYLYAAFADVTPLSPKLQMVPALVAKMVPTVNAVNYALGSETICRGIWGCLSPQKRERDRAR       
RGR_musMus  MAATRALPAGLGELEVLAVGTVLLMEALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLRRWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCTGRQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLPVNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYALHREMVCRGTWQCLSPQKSKKDRTQ       
RGR_ratNor  MTATRALPAGFGELEVLAIGIVLLMEALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLRRWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCTGRQLAWDTAIPLVLFVWLSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFMEQKLSRSGHLQVNTTLPGRMLLLGWGPYALLYLYAAVADVSFISPKLQMVPALIAKTMPTINAINYALRSEMVCRGTWQCRSAQKSKQDRTQ       
RGR_speTri  MAETAALPAGFGELEVLAVGTVLLVEALSGLSLNGLTIFSFCKTPELRTPNHLLLLSLAVADSGISLNALIAAISSLLRRWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCTGSQLAWNTAIPLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRGDRNFISFLFTMAFFNFFVPLFITLTSYRLMEQKLARSGHLQVNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQMVPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ       
RGR_dipOrd  MATSGDLPTGFGELEVLTVGTVLLVEALSGLSLNTLTIFSFCKTPELRTPIHLLDLSLAVADSGISLNALIAAISSLEWHWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCTGSLLGWDTAVSLVIFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDRNFTSFLFTMAFFNFLVPLFITLTSYQLMKQKFARSGRLQVNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQMVPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ       
RGR_cavPor  MATSEALPAGFGELEVLAVGTVLLLEGLCGLSLNGLTVVSFWKSPALRTPNHLLVLSLALADSGLSLNALVAAGSSLLRHWPYGSGHCQALGFQGFTTALASISGTAALSWGRCHHHCTRGRLTWSTAVPLVLFVWLSSAFWAALPLLGWGRYDYEPLGTCCTLDYSTGDRNFTSFLFTMAFFNFLVPLFITVTSCQLMERHLARSSRLQVSVRQPARTLLLCWGPYALLYLYAVLADAHTLSPRLQMVPALIAKTVPTINAINYALCNELLCGGFSLGLLPQKGKQDRTQ       
RGR_oryCun  MAEPGTLPPGFEELEVLAVGTVLLVEALSGLSLNGLTIFSFCKTPELWTPSHLLVLSLAVADSGISLNALIAAVSSLLRRWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCTGSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDRNFISFLITMAFFNFLMPLFITLTSYSLMEQKLSKSGRLQVNTTLPGRTLLFCWGPYAVLYLCAAVADMSSITLKLQMVPALIAKTVPTVNAVNYALGSEVIRRGIWQCLLPQRSVRGRAQ       
RGR_ochPri  MAEPGTLPPGFEELEVLAVGTVLLVEALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLRRWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCTGSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDRNFISFLVTMAFFNFLMPLFIMLTSYSLMEQKLAKSGRLQVNTTLPARTLLFCWGPYAILCLCATVMDMSTVSPKLLMVPALIAKAVPTVNAINYALGSEVIRRGIWQCLLPQRSVRDRAQ       
RGR_bosTau  MAESGTLPTGFGELEVLAVGTVLLVEALSGLSLNILTILSFCKTPELRTPSHLLVLSLALADSGISLNALVAATSSLLRRWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCTGSRLDWNTAVSLVFFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDRNFTSFLFTMAFFNFLLPLFITVVSYRLMEQKLGKTSRPPVNTVLPARTLLLGWGPYALLYLYATIADATSISPKLQMVPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ       
RGR_turTru  MAESGALPSGFGELEVLAVGTVLLVEALSGLSLNSLTILCFCKNPELRTPSHLLVLSLALSDSGISLNALMAATSSLLRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTGSRLDWNTAVSLVFFVWLSSAFWATLPLLGWGHYDREPLGTCCTLDYSRRDRNFTSFLFTMAFFNFLLPLFITVISYRLMEQKLGKTGRPPVNTVLPARTLLFGWGPYALLYLYAAVADVTSISPKLQMVPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ       
RGR_susScr  MAEPGALPTGFGELEVLAVGTLLLVEALSGLSLNSLTILSFCKTPELRTPSHLLVLSLALADSGISLNAFVAATSSLLRRWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCTRSRLDWNTAVSLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRVDRNFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPPVNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQMVPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ       
RGR_vicVic  MAESRALPTGFGELEVLAVGMVLLVEALSGLSLNSLTILSFCKTPELRTPNHLLVLSLALADSGISLNALVAATSSLLRRWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCTGSRLDWNTAVSLVFFVWLSSTCWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPPVNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQMVPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ       
RGR_equCab  MAESGSLPTGFRELEVLAVGTVLLVEALAGLSLNSLTILSFCKTPELRTPSHLLVLSLAVADSGLSLNALVAATSSLLRRWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTRSRLAWNTAVFLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLLTMAFFNLLLPLLITLTSYRLMEQKLGKTGQLQVNTTLPARTLLLCWGPYALLYLYATVADATSISPKLRMVPALVAKTVPTINAVNYALGSEMLHRGIWQCLSPQKSERDRAQ       
RGR_canFam  MADSGALPAGFGELEVLAVGTVLLVEALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLRRWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCTRGQLAWNTAISLVLCVWLSSVFWAALPLLGWGRYDYEPLGTCCTLDYSRVDRNFTSYLFTMAFFNFFLPLLITLVSYRLMEQKLKKPGHLQVSTTVPARTLLLCWGPYALLYLYATVADVRSVPPKLQMVPALIAKAAPTINAIHYALGGDMVHGGLWQCLSPQRSQPDRAR       
RGR_felCat  MAESGSLPTGFGELEVLAVGMVLLVEALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLRRWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCSGSQLAWNTAISLVICVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDRNFTSFLFTMAFFNFFMPLFITFISYRLMEQKLRKTGHLQVNTTLPARTLLFGWGPYALLYLYATIADVSSVSPKLQMVPALIAKAAPTINAINYALGSEMVHRGIWQCLSPQGSGLDRAR       
RGR_pteVam  MAESRSLPTVFWELEVLAVGTVLMVEALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLRRWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCTGSRLAWNTAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRRDRNFTSFLFTMAFFNFVLPLFITLTSYQLMEQKLGKTGHPQVNTTLPARTLMLCWGPYALLYLYAAVMDVASISPKLQMVPALIAKMAPTINAVNYALGSEMVQRGIWQCLSPQRSERDHAQ       
RGR_myoLuc  MAEAGSLPTGFGELEVLAVGVVLLVEALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLRRWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCTGSRLAWRTAASLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCSLGYARGSRNFTSFLFLMAFFNFLLPLFITFTSYRLMEQKLGRTRPPQVNTTLPARTLLLGWGPYALLHLCAALAGTALIPPRLQVVPALIAKMVPTVNAVNYALGSEMVQRGIWQCLSPQRSERDHAQ       
RGR_sorAra  MTESGALPAGFKELKMLAVGTLLLWGALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLRRWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCTGRQLAWDVAIALVIFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGGRNFVSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKMGQPQVNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQMVPALIAKTVPTVNALHYGLGSGMVQNGFRKGLWLQRRERERAL       
RGR_eriEur  MTESGALPAGFKELKMLAVGTLLLWGALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLRRWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCTRSRLAWNTAVFLVFFVWVSSVFWAALPLLGWGHYDYEPLGTCCTLDYSSGDRNFISFLFTMAFFNFLLPLFITLISYQLMEQKLRKTGHPQVNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQMVPALIAKMVPTVNAVHYVLGSEKVHKGFWQCFSPQRSEQDRAR       
RGR_loxAfr  MAEPGHLPAGFQELEVLTVGTVLLLEALSGLSLNGLTILSFCKIPELRTPGHLLVLSLALADSGISLNALVAAMSSLRRRWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCTRSRLAWSSASALVLFVWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDRNSTSFLLTMAFFNFLLPLFITLTSYRLMEQKLKKKGPLQVNTTLPARTLLLGWGPYALLYLCAAATDMTSISPRLQMVPALVAKAVPVINACHYALGSEVVRGGIWQYLSRQRGESPLRARDRTH  
RGR_proCap  MADPRPLPTGFGELEVLTVGTVLLVEALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRGRWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCTGSKLAWSSAGALVLFMWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDRNSTSFLFTMAFFNFLLPLFITLASYRLMEQKLKKEGPLQVNTTLPARTLLLGWGPYALLYLYTAITDVNSISPKLQMVPALIAKAVPIVNACHYALGSETVHRGIWQCLSRQRGESPPRTRDRTQ  
RGR_echTel  MVEPRTLPPGFGELEVLAVGTVLLVEALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRGHWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCTGSQFTWSSASTLVLFMWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDRNFTSFLFTMTFFNFSMPILVTLTSYQLMQQKLKKSGPLQVNTTLPTRTLLLGWGPYALLYLCAACTDVTGISPKLQMVPAIVAKAVPIVNACHYALGNKVLRRGIWQFLS-QQSGRPLSSQDRTQ  
RGR_dasNov  MAGSGVLPPGFGELEVLAVGTVLLVEALSGLVLNGLAIISFCKTPELRSPSRLLVLSLALADSGVSLNALVAATSSLLRRWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCIGRRLAWSTAGCLVLCLWMAAAFWAALPLLGWGLYDYEPLGTCCTLDYSRGDRNFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQVSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQMVPALIAKTMPTVNALYYALGRESVHRNA                      
RGR_choHof  MAESRVLPTGFGELEVLAVGIVLLVEALSGLTLNGLTLFSFCKTPELQRPSHLLVLSLALADSGVSLNALLAATASLIGRWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCTGSQLSWSTAGSLVLCVWLSSVFWATLPILGWGHYDYEPLGTCCTLGYSRGDRNFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQVSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQMVPALIAKTMPTINAFQYALGSETVCRDIWQCLPRLRSMGRSSGHD     
RGR_ornAna  MVTSHPLPEGFTEIEVFAIGTALLVEALLGLCLNGLTIASFRKIKELRTPSNLLVVSLALADSGICLNALMAALSSFLRHWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCSRSKPQWGTAVSTVLFAWGFSAFWSMMPILGWGQYDYEPLRTCCTLDYSKGDRNFTTYLFAVAFFNFVIPLFIMLTSYQSIEQRFKKSGLFKLNTRLPTRTLLFCWGPYALLCFYATVENVTFISPKLRMIPALIAKTVPVIDAFTYALRNEDYRGGIWQFLTGQKI---ERVEVENKIK
RGR_anoCar  MVTAYPVPEGFTDLEVFVIGTALLVEALLGFSLNMLTIVSFWKIKELRTPGNFLVFNLALSDCGICFNAFIAAFSSFLRYWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCTGNKLQWGSVIPMTIFLWLFSGFWAAMPLLGWGEYDYEPLRTCCTLDYTKGDRNYITYLIPLALFHFMIPGFIMLTAYQAIDHKFKKTGQFKFNTGLPVKSLVICWGPYSFLCFYAAVESVTFISPKILMIPAVIAKSSPAANALIYALGNENYQGGIWQFLTGQKI---EKAEVDNKTK
RGR_galGal  MVTSHPLPEGFTEIEVFAIGTALLVEALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLRYWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCTRSKLQWSTAISMMVFAWLFAAFWATMPLLGWGEYDYEPLRTCCTLDYSKGDRNYITFLFALSIFNFMIPGFIMMTAYQSIHQKFKKSGHYKFNTGLPLKTLVICWGPYCLLSFYAAIENVMFISPKYRMIPAIIAKTVPTVDSFVYALGNENYRGGIWQFLTGQKI---EKAEVDSKTK
RGR_taeGut  MVTAHPLPEGFTEIEVFAIGTALLVEALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLRYWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCTRSRLQWSTAVSMMVFAWLFAAFWSVMPLLGWGKYDYEPLRTCCTLDYSKGDRNYVTFLFALSTFNFMIPGFIMMTAYQSIHQKFRKTGHFKFNTGLPLKTLVICWGPYCLLCTYAAVENVMFIPPKYRMIPALIAKTVPTVDAFIYALGNENYRGGIWQFLTGQKI---EKAEVDNKTK
RGR_xenTro  MVTSYPLPEGFTETEVFAIGTTLLVEALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLRYWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCTRSKLHWSTAVSVVFFIWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDRNYISYLFTMAFFEFLVPLFILMTAYQSIYQKMKKSGQIRFNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRMIPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKL---EKAETDNKTK
RGR_xenLae  MVTSYPLPEGFTETEVFAIGTTLLIEALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLRYWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCTRSKLHWGTAVSMVLFVWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDRNFTSFLFTMAFFEFLVPVFILLTAYQSIYQKMKKSGQIRLNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRMMPALLAKISPAVNAYVYGLGNENYRGGIWLYLTGQKL---EKAETDSRTK
RGR1_danRe  MVTSYPLPEGFSEFDVFSLGSCLLVEGLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLRYWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCTRTKLQWSSAITLVLFTWLFTAFWAAMPLFGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAKFNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRMIAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKI---ESPAIENKSK
RGR1_pimPr  MVT-YPLPEGFSDFDVFSLGSCLLVEGLLGFFLNAVTVVAFLKIRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLRYWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCTRTKLQWSSAITLVIFIWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMSIFNMGIQVFVVLSSYQSIERKFQKSGQAKFNCSTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRMMAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK
RGR1_osmMo  MVSSYPLPDGFSDFDVFSLGSCLLVEGLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISSNATIAAFSSFLRYWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCTRTKLQWSSAITLVMFIWLFTAFWSAIPLIGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMAIFNMAIQIFVVLSSYQSIDQKFKKTAKPKFNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRMMAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK
RGR1_takRu  MVSSYPLPEGFSDFDVFSLGSCLLVEGLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISMNATIAAFSSFLRYWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCTRTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPRFNPSTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRMMAPILAKTCPTINVFLYALGNENYRGGIWQFLTGEKI---EAPQIENKSK
RGR1_tetNi  MVSSYPLPEGFSDFDVFSLGSCLLVEGLLGFFLNAVTVVAFFKVRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLRYWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCTRTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDRNYVSYLVPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPRFNPNTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRMMAPILAKTCPTVNVFLYALGNENYRGGIWQFLTGEKI---ETPQLENKTK
RGR1_gasAc  MVSSYPLPDGFTDFDVFSLGSCLLVEGLLGILLNAVTIAAFLKVRELRTPSNFLVFSLAVADIGISMNATIAAFSSFLRYWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCTRTKLQWSSAITLAVFVWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYTKGDRNYVSYLIPMAIFNMAIQVFVVMSSYQSIAQKFKKTGNPRFNPNTPLKAMLFCWGPYGILAFYAAVENATLVSTKLRMMAPILAKTSPTFNVFLYALGNENYRGGIWQLLTGEKI---DVPQIENKSK
RGR1_gadMo  MVSAYPLPEGFSDFDVFSFGSFLLVEGLLGIILNAVTIVAFCKVKELRTPSNFLVFSLAMADIGISMNASVAAFSSFLRYWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCTRTELQWSSAVTLSVFIWLFSAFWSAMPLIGWGTYDYEPLRSCCTLDYTKGDRNYVSYLIPMTVFNMVVQIFVVMSSYQSIDQKFKKTAKPKFNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRMMAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK
RGR1_oryLa  MATSYPLPEGFSEFDVFSLGSCLLVEGLLGIFLNSVTIVAFLKVRELRTPSNFLVFSLAMADIGISMNATIAAFSSFLRYWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCTRTKLQWSTAITLAVLVWIFTAFWAAMPLIGWGEYDYEPLRTCCTLDISKGDRNYVSYVIPMSIFNMGIQVFVVMSSYQSIAQKFQKTGNPRFNASTPLKTLLFCWGPYGILAFYAAVADANLVSPKIRMIAPILAKTSPTFNPLLYALGNENYRGGIWQFLTGEKI---HVPQDDNKSK
RGR_calMil  MVSSYPLPEGFTDFEVFGLGTALLVEGLVGLLLNGLTLLAFYKIKELRTPSNLLITSLALSDFGISMNAFIAAFSSFLRYWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCSRSRLQWSSAITVTVFIWGIAAFWSAMPLLGWGVYDYEPLRTCCTLDYSKGDRNFISFFIIMGSFEFIFPIFIMLSSYQSCKSKFKKNGQVKFNTGLPVKTLIFCWGPYSLLCFYATIENITILSPKLRMIPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKL---EKAETDNKTK
RGR2_danRe  MA-SYPLPEGFTDFDMFAFGSALLVGGLLGFFLNAISVLAFLRVREMQTPNNFFIFNLAVADLSLNINGLVAAYACYLRHWPFGSEGCQLHAFQGMVSILAAISFLGAVAWDRYHQYCTKQKMFWSTSITISCLIWILAVFWAAMPLIGWGVFDFEPLRTCCTLDYSQGDRGYITYMLTITVLYLAFPVLVLQSSYSAIHAYFKKTHHYRFNTGLPLKALLFCWGPYVVVCSLACFEDVSVLSPRLRMVLPVLAKTSPIFHAVLYAYGNEFYRGGVWQFLTGQKSADKKK        
RGR2_pimPr  MA-SYALPEGFSDFDMFAFGSALLVGGLLGFFLNLISVLAFLRVREIQTPNNFFIFNLAVADLSLNINGLVAAYASYLRYWPFGSEGCQIHGFQGMVSILASISFLGAIAWDRYHLYCTKQKMFWSTSGTISALIWILAVFWAALPLIGWGVFDFEPMRTCCTLDYTIGDRNYISYMLTITVLYLAFPVLIMQSSYNGIYAHFKKTHHFKFNTGLPLKMLLFCWGPYVLMCTYACFENASLVSPKLRMVLPVLAKTSPIFHAAMYAYGNEFYRGGIWQFLTGQKPADKKK        
RGR2_tetNi  MA-AYTLPEGFTEFDMFTFGTALLVGGVLGFFLNAISIVSFLTVKEMRNPSNFFVFNLALADISLNVNGLIAAYASYLRYWPFGQDGCSYHAFHGMISVLASISFMAAIAWDRYHQYCTRQKLFWSTTLTMSSIIWILSIFWSAVPLMGWGVYDFEPMRTCCTLDYTRGDRDYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHRFNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRMLLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK    
RGR2_hipHi  MA-AFTLPEGFTDFDMFTFGTALLVGGMLGFVLNAISIVSFLTVKEMRNPSNFFVFNLAVADLCLNINGLTAAYASYLRYWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCTRQKLFWSTTLTMSGIIWILSIFWAAVPLMGWGAYYFEPMKTCCTLDYTRGDRDYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHRFNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRMLLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK    
RGR2_gasAc  MA-AFALPEGFTEFDMFTFGSALLVGGLIGFFLNAISIASFLRVKEMWNPSNFFVFNLAVADICLNVNGLTAAYASYLRYWPFGQDGCTFHAFQGMIAVLASISFMGVIAWDRYHQYCTRQKLFWSTTLTMSAIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTKGDRDYVTYMLTLVFLYLMFPALTMWSCYDAIHKHFKKIHLHKFNTSTPLRVLLMCWGPYVLMCIYACFENVKVVSPKLRMLLPVVAKTNPIFNALLYSFGNEFYRGGVWHFLTGQKMVDPVVKKSK    
RGR2_oryLa  MG-THTLPEGFTDFDMFTFGSALLVGGLLGFFLNAISILAFLRVKEMRSPSSFLVFNLALADISLNINGLTAAYASYLRYWPFGQEGCDYHGFQGMISVLASISFMAAIAWDRYHQYCTRQKLFWSTSITISLIIWILSILWSAFPLMGWGVYDFEPMRIGCTLDYTKGDRDYITYMLSLVFFYLMFPAFIMLSCYDAIYKHFKKIHYYRFNTSLPLRVMLMCWGPYVLMCIYACFENVKLVSPKLRM-LPVIAKTNPFFNALLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSKQK  
RGR2_gadMo  MA-AYALPEGFEEFDMFTFGTALLVGGMIGFILNAITIVAYLRVKEMRTPSNFFVFNLALADLSLNINGLTAAYASYARQWPFGQSGCSYHGFQGMISVLASISFMAAISWDRYHQYCTRQKLFWSTTVTMCCIVWVLSVFWAALPLIGWGVYDFEPMRVGCTLDYTIGDRDYITYMLSLVVFYLLFPAYTMMSSYDAINKHFRKIHLQKFNTKLPLSVMLACWGPYVLMCVYACFENVKIVSPKLRMVLPVLAKTNPISNALLYSFGNESYRSGVWHFLTGQKFVEPSFKKIK    
RGR2_oncMy  MA-AYTLPEGFSDFDMFAFGSALLVGGLLGFFLNAISILAYISVKQMRTPSNFLVFNLAVADIVLNLNGLIAAYASFYRHWPWGQDGCSNHAFMGMTAVLASISFLAAIAWDRYHQYVTNQKLFWSTAWTISIIIWGLAIIWAAVPLIGWGVYDFEPMRTCCTLDYTKGDNDYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHRWNTSIPLRVLLFCWGPYEIMCIYACFENVKIVSPKLRMLLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR  
RGR2_esoLu  MA-AYTLPEGFSDFDMVAFGSALLVGGLAGFFLNATSILAFVSVKQMRTPSNFLVFNLAVADIMLNTSGLIAAYASSYRHWPWGQDGCSNHAFFGMTAVLTSISFLAVIAWDRYHQYVTNQKLFWSTAWTFSIIIWGMAIFWAYVPLTGWGVYDFEPMRTCCTLDYTKGDNDYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHRWNTSIPLRVLLFCWGPYEIMCIYACFENVKIVSPKLRMLLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR  
Consensus   M.....LP.GF.#......G..LLv..$.G..LN..t...F....#$rtP...l!..LA.aD.g...Na..aA..S.lr.WP.G..gCq.HgFqGf..aLaSI...aAiaW.Ryh..Ct...$.W..a.......W....fW.a.Pl.GWG.Y#%EP$.tCCTLdY..gDR#...%$.....f....p......sY...............nt..P...$l..WGPY..$..yA...#....sPkl.M.....AK..P..#a..Y.lg.#....g.w..l..q...............

The three cytoplasmic loops and C-terminus aligned: GRY domain and possibly kinase sites

 RGR_homSap TIFSFCKTPELRTPCH GRYHHYCTRSQLAWNSAVS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKRE-----KDRTK*
 RGR_panTro TIFSFCKTPELRTPCH GRYHHYCTRSQLAWNSAIS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSE-----KDRTK*
 RGR_gorGor TIFSFCKTPELRTPCH GRYHHYCTGSTLACKSAVS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSK-----KDRTK*
 RGR_ponPyg TIFSFCKTPELRTPCH GRYHHYCTGSQLAWNSAIS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSE-----KDRTK*
 RGR_nomLeu TIFSFCKTPELRTPCH GRYHHYCTGSQLAWNSAIS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSE-----KDRAK*
 RGR_macMul TIFSFCKTPELRTPCH GRYHHYCTRSQLAWNSAIS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSE-----KDRAK*
 RGR_papHam TIFSFCKTPELRTPCH GRYHHYCTRSQLAWNSAIS YSLMEQKLGKSGHLQVNTTLPART NEMVCRGIWQCLSPQKSE-----KDRAK*
 RGR_calJac TIFSFCKTPELRTPCH GRYHHYCTGSQLAWNSAIS YRLMEQKLGKSGHLQVNTTLPART NEMICRGIWQCLSPQKSE-----KDRTK*
 RGR_tarSyr TIFSFCKTPELRTPCH GRYHHYCTGSQLAWNTAIS YRLMEQKLGKSGHLQVNTTLPIRT SEMVCRGIWQCLSPHSSE-----QDRAK*
 RGR_otoGar TIFSFCKTPELRTPCH GRYHHYCTGRPLAWSTAIS YQLMEQKLRRSGHLQVNTTLPART SEMVCRGIWQCLSLQRSK-----QDGAK*
 RGR_micMur TIFSFCKTPELRTPCH GRYHHYCTGSPLAWSTAIS YQLMEQKLKKSGHLQVNTTLPART SETVCRGIWQCLSPQRSE-----QDRAK*
 RGR_tupBel TVFSFCKSPELRTPSH GRYHQYCTGSPLAWSTAIS YWLMEEKLRKGGRLQVNTTLPSRT SETICRGIWGCLSPQKRE-----RDRAR*
 RGR_musMus TIFSFCKTPDLRTPSN GRYHHYCTGRQLAWDTAIP YRFMEQKFSRSGHLPVNTTLPGRM REMVCRGTWQCLSPQKSK-----KDRTQ*
 RGR_ratNor TIFSFCKTPDLRTPSN GRYHHYCTGRQLAWDTAIP YRFMEQKLSRSGHLQVNTTLPGRM SEMVCRGTWQCRSAQKSK-----QDRTQ*
 RGR_speTri TIFSFCKTPELRTPNH GRYHHYCTGSQLAWNTAIP YRLMEQKLARSGHLQVNTTLPTRT NELLCGGFSLGLLPQKGK-----QDRTQ*
 RGR_dipOrd TIFSFCKTPELRTPIH GRCHHHCTGSLLGWDTAVS YQLMKQKFARSGRLQVNTTLPTRT NELLCGGFSLGLLPQKGK-----QDRTQ*
 RGR_cavPor TVVSFWKSPALRTPNH GRCHHHCTRGRLTWSTAVP CQLMERHLARSSRLQVSVRQPART NELLCGGFSLGLLPQKGK-----QDRTQ*
 RGR_oryCun TIFSFCKTPELWTPSH GRYHHYCTGSQLAWNTAVL YSLMEQKLSKSGRLQVNTTLPGRT SEVIRRGIWQCLLPQRSV-----RGRAQ*
 RGR_ochPri TIFSFCTSPELRTPSH GRYHHYCTGSQLAWNTAVL YSLMEQKLAKSGRLQVNTTLPART SEVIRRGIWQCLLPQRSV-----RDRAQ*
 RGR_bosTau TILSFCKTPELRTPSH GRYHHFCTGSRLDWNTAVS YRLMEQKLGKTSRPPVNTVLPART SEMVHRGIWQCLSPQRRE-----HSREQ*
 RGR_turTru TILCFCKNPELRTPSH GRYHHYCTGSRLDWNTAVS YRLMEQKLGKTGRPPVNTVLPART SEMVHRGIWQCLSPQRRE-----HSREQ*
 RGR_susScr TILSFCKTPELRTPSH GRYHHYCTRSRLDWNTAVS YRLMEQKLGKTGRPPVNTILPART GEMVHRGIWQCLSPQRRE-----RDREQ*
 RGR_vicVic TILSFCKTPELRTPNH GRYHHYCTGSRLDWNTAVS YRLMEQKLGKTGRPPVNTILPART GEMVHRGIWQCLSPQRRE-----RDREQ*
 RGR_equCab TILSFCKTPELRTPSH GRYHHYCTRSRLAWNTAVF YRLMEQKLGKTGQLQVNTTLPART SEMLHRGIWQCLSPQKSE-----RDRAQ*
 RGR_canFam TILSFCKTPELRTPTH GRYHHYCTRGQLAWNTAIS YRLMEQKLKKPGHLQVSTTVPART GDMVHGGLWQCLSPQRSQ-----PDRAR*
 RGR_felCat TILSFCKTPELRTPTH GRYHHYCSGSQLAWNTAIS YRLMEQKLRKTGHLQVNTTLPART SEMVHRGIWQCLSPQGSG-----LDRAR*
 RGR_myoLuc TIFSFCTSPELRTPSH GRYHHYCTGSRLAWRTAAS YRLMEQKLGRTRPPQVNTTLPART SEMVQRGIWQCLSPQRSE-----RDHAQ*
 RGR_pteVam TILSFCKNPELRTPIH GRYHHYCTGSRLAWNTAVS YQLMEQKLGKTGHPQVNTTLPART SEMVQRGIWQCLSPQRSE-----RDHAQ*
 RGR_sorAra TILSFCKNPELRTPIH GRYHHYCTGRQLAWDVAIA YRLMEQKLGKMGQPQVNTTLPART SGMVQNGFRKGLWLQRRE-----RERAL*
 RGR_eriEur TILSFCKNPELRTPIH GRYHHHCTRSRLAWNTAVF YQLMEQKLRKTGHPQVNTTLPART SEKVHKGFWQCFSPQRSE-----QDRAR*
 RGR_loxAfr TILSFCKIPELRTPGH ERYHHYCTRSRLAWSSASA YRLMEQKLKKKGPLQVNTTLPART SEVVRGGIWQYLSRQRGESPLRARDRTH*
 RGR_proCap TILSFYKIPELRTPGH ERYHHYCTGSKLAWSSAGA YRLMEQKLKKEGPLQVNTTLPART SETVHRGIWQCLSRQRGESPPRTRDRTQ*
 RGR_echTel TILSFYKIPELRTPGH ERYHHYCTGSQFTWSSAST YQLMQQKLKKSGPLQVNTTLPTRT NKVLRRGIWQFLS-QQSGRPLSSQDRTQ*
 RGR_dasNov AIISFCKTPELRSPSR ERCHRHCIGRRLAWSTAGC YRLMAQKLKRSGHVQVSTALPGRL RESVHRNA*
 RGR_choHof TLFSFCKTPELQRPSH ERYRHHCTGSQLSWSTAGS YRLMAQKLKRSGHVQVSTALPGRL SETVCRDIWQCLPRLRSMGRSSGHD*
 RGR_ornAna TIASFRKIKELRTPSN DRYLRHCSRSKPQWGTAVS YQSIEQRFKKSGLFKLNTRLPTRT NEDYRGGIWQFLTGQKIERVEVENKIK*
 RGR_anoCar TIVSFWKIKELRTPGN DRHHQYCTGNKLQWGSVIP YQAIDHKFKKTGQFKFNTGLPVKS NENYQGGIWQFLTGQKIEKAEVDNKTK*
 RGR_galGal TIISFRKIKELRTPSN DRYHHYCTRSKLQWSTAIS YQSIHQKFKKSGHYKFNTGLPLKT NENYRGGIWQFLTGQKIEKAEVDSKTK*
 RGR_taeGut TIISFRKIKELRTPSN DRYHHYCTRSRLQWSTAVS YQSIHQKFRKTGHFKFNTGLPLKT NENYRGGIWQFLTGQKIEKAEVDNKTK*
 RGR_xenTro TLLSFYKIRELRTPSN DRYHQYCTRSKLHWSTAVS YQSIYQKMKKSGQIRFNTSMPVKS NENYRGGIWQYLTGQKLEKAETDNKTK*
 RGR_xenLae TLLSFYKIRELRTPSN DRYHQYCTRSKLHWGTAVS YQSIYQKMKKSGQIRLNTSMPVKS NENYRGGIWLYLTGQKLEKAETDSRTK*
 RGR1_danRe TVIAFLKIRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIDKKFKKTGQAKFNCGTPLKT NENYRGGIWQLLTGQKIESPAIENKSK*
 RGR1_pimPr TVVAFLKIRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIERKFQKSGQAKFNCSTPLKT NENYRGGIWQLLTGEKIEVPQIENKSK*
 RGR1_osmMo TVVAFLKVRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIDQKFKKTAKPKFNARTPLKT NENYRGGIWQLLTGEKIEVPQIENKSK*
 RGR1_takRu TVVAFLKVRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIAEKFKKTGNPRFNPSTPLKA NENYRGGIWQFLTGEKIEAPQIENKSK*
 RGR1_tetNi TVVAFFKVRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIAEKFKKTGNPRFNPNTPLKA NENYRGGIWQFLTGEKIETPQLENKTK*
 RGR1_gasAc TIAAFLKVRELRTPSN DRYHQYCTRTKLQWSSAIT YQSIAQKFKKTGNPRFNPNTPLKA NENYRGGIWQLLTGEKIDVPQIENKSK*
 RGR1_gadMo TIVAFCKVKELRTPSN DRYHQYCTRTELQWSSAVT YQSIDQKFKKTAKPKFNARTPLKT NENYRGGIWQLLTGEKIEVPQIENKSK*
 RGR1_oryLa TIVAFLKVRELRTPSN DRYHQYCTRTKLQWSTAIT YQSIAQKFQKTGNPRFNASTPLKT NENYRGGIWQFLTGEKIHVPQDDNKSK*
 RGR_calMil TLLAFYKIKELRTPSN DRYHQNCSRSRLQWSSAIT YQSCKSKFKKNGQVKFNTGLPVKT NENYRGGIWQYLTGQKLEKAETDNKTK*
 RGR2_danRe SVLAFLRVREMQTPNN DRYHQYCTKQKMFWSTSIT YSAIHAYFKKTHHYRFNTGLPLKA NEFYRGGVWQFLTGQKSAD-----KKK*
 RGR2_pimPr SVLAFLRVREIQTPNN DRYHLYCTKQKMFWSTSGT YNGIYAHFKKTHHFKFNTGLPLKM NEFYRGGIWQFLTGQKPAD-----KKK*
 RGR2_tetNi SIVSFLTVKEMRNPSN DRYHQYCTRQKLFWSTTLT YDSIYKHFKKVHQHRFNTSMPLRV NEFYRGGVWHFLTGHKIVDPVL-KKSK*
 RGR2_hipHi SIVSFLTVKEMRNPSN DRYHQYCTRQKLFWSTTLT YDSIYKHFKKVHQHRFNTSMPLRV NEFYRGGVWHFLTGHKIVDPVL-KKSK*
 RGR2_gasAc SIASFLRVKEMWNPSN DRYHQYCTRQKLFWSTTLT YDAIHKHFKKIHLHKFNTSTPLRV NEFYRGGVWHFLTGQKMVDPVV-KKSK*
 RGR2_oryLa SILAFLRVKEMRSPSS DRYHQYCTRQKLFWSTSIT YDAIYKHFKKIHYYRFNTSLPLRV NEFYRGGVWNFLTGQKIVEPDV-KKSKQK*
 RGR2_gadMo TIVAYLRVKEMRTPSN DRYHQYCTRQKLFWSTTVT YDAINKHFRKIHLQKFNTKLPLSV NESYRSGVWHFLTGQKFVEPSF-KKIK*
 RGR2_oncMy SILAYISVKQMRTPSN DRYHQYVTNQKLFWSTAWT YDAIHAYFKKIHKHRWNTSIPLRV NEFYRGGVWQFLTGQKFTEPVVV-KLKGR*
 RGR2_esoLu SILAFVSVKQMRTPSN DRYHQYVTNQKLFWSTAWT YDAIHAYFKKIHKHRWNTSIPLRV NEFYRGGVWQFLTGQKFTEPVVV-KLKGR*

The four cytoplasmic loops differences: 

RGR_homSap  TIFSFCKTPELRTPCH  GRYHHYCTRSQLAWNSAVS  YSLMEQKLGKSGHLQVNTTLPART  NEMVCRGIWQCLSPQKREKDRTK  
RGR_panTro  ................  .................I.  ........................  ................S......  
RGR_gorGor  ................  ........G.T..CK....  ........................  ................SK.....  
RGR_ponPyg  ................  ........G........I.  ........................  ................S......  
RGR_nomLeu  ................  ........G........I.  ........................  ................S....A.  
RGR_macMul  ................  .................I.  ........................  ................S....A.  
RGR_papHam  ................  .................I.  ........................  ................S....A.  
RGR_calJac  ................  ........G........I.  .R......................  ...I............S......  
RGR_tarSyr  ................  ........G......T.I.  .R...................I..  S.............HSS.Q..A.  
RGR_otoGar  ................  ........GRP...ST.I.  .Q......RR..............  S............L.RSKQ.GA.  
RGR_micMur  ................  ........G.P...ST.I.  .Q......K...............  S.T............RS.Q..A.  
RGR_tupBel  .V.....S......S.  ....Q...G.P...ST.I.  .W...E..R.G.R........S..  S.TI.....G........R..AR  
RGR_musMus  .........D....SN  ........GR....DT.IP  .RF....FSR....P......G.M  R......T........SK....Q  
RGR_ratNor  .........D....SN  ........GR....DT.IP  .RF.....SR...........G.M  S......T...R.A..SKQ...Q  
RGR_oryCun  ...........W..S.  ........G......T..L  ........S...R........G..  S.VIR.......L..RSVRG.AQ  
RGR_ochPri  ......TS......S.  ........G......T..L  ........A...R...........  S.VIR.......L..RSVR..AQ  
RGR_speTri  ..............N.  ........G......T.IP  .R......AR...........T..  ..LL.G.FSLG.L...GKQ...Q  
RGR_dipOrd  ..............I.  ..C..H..G.L.G.DT...  .Q..K..FAR..R........T..  ..LL.G.FSLG.L...GKQ...Q  
RGR_cavPor  .VV..W.S.A....N.  ..C..H...GR.T.ST..P  CQ...RH.AR.SR...SVRQ....  ..LL.G.FSLG.L...GKQ...Q  
RGR_bosTau  ..L...........S.  .....F..G.R.D..T...  .R........TSRPP...V.....  S...H..........R..HS.EQ  
RGR_turTru  ..LC...N......S.  ........G.R.D..T...  .R........T.RPP...V.....  S...H..........R..HS.EQ  
RGR_susScr  ..L...........S.  ..........R.D..T...  .R........T.RPP...I.....  G...H..........R..R..EQ  
RGR_vicVic  ..L...........N.  ........G.R.D..T...  .R........T.RPP...I.....  G...H..........R..R..EQ  
RGR_equCab  ..L...........S.  ..........R....T..F  .R........T.Q...........  S..LH...........S.R..AQ  
RGR_felCat  ..L...........T.  .......SG......T.I.  .R......R.T.............  S...H..........GSGL..AR  
RGR_canFam  ..L...........T.  .........G.....T.I.  .R......K.P.....S..V....  GD..HG.L.......RSQP..AR  
RGR_myoLuc  ......TS......S.  ........G.R...RT.A.  .R.......RTRPP..........  S...Q..........RS.R.HAQ  
RGR_pteVam  ..L....N......I.  ........G.R....T...  .Q........T..P..........  S...Q..........RS.R.HAQ  
RGR_eriEur  ..L....N......I.  .....H....R....T..F  .Q......R.T..P..........  S.K.HK.F...F...RS.Q..AR  
RGR_sorAra  ..L....N......I.  ........GR....DV.IA  .R........M.QP..........  SG..QN.FRKG.WL.R..RE.AL  
RGR_loxAfr  ..L....I......G.  E.........R...S..SA  .R......K.K.P...........  S.V.RG....Y..R.RG.SPLRARDRTH  
RGR_proCap  ..L..Y.I......G.  E.......G.K...S..GA  .R......K.E.P...........  S.T.H........R.RG.SPPRTRDRTQ  
RGR_echTel  ..L..Y.I......G.  E.......G..FT.S..ST  .Q..Q...K...P........T..  .KVLR.....F..Q.SGR-PLSSQDRTQ  
RGR_dasNov  A.I.........S.SR  E.C.RH.IGRR...ST.GC  .R..A...KR...V..S.A..G.L  R.S.H.NA  
RGR_choHof  .L.........QR.S.  E..R.H..G...S.ST.G.  .R..A...KR...V..S.A..G.L  S.T...D.....PRLRSMGRSSGHD  
RGR_ornAna  ..A..R.IK.....SN  D..LRH.S..KPQ.GT...  .QSI..RFK...LFKL..R..T..  ..DYRG....F.TG..I---ERVEVENKIK  
RGR_anoCar  ..V..W.IK.....GN  D.H.Q...GNK.Q.G.VIP  .QAIDH.FK.T.QFKF..G..VKS  ..NYQG....F.TG..I---EKAEVDNKTK  
RGR_galGal  ..I..R.IK.....SN  D.........K.Q.ST.I.  .QSIH..FK....YKF..G..LK.  ..NYRG....F.TG..I---EKAEVDSKTK  
RGR_taeGut  ..I..R.IK.....SN  D.........R.Q.ST...  .QSIH..FR.T..FKF..G..LK.  ..NYRG....F.TG..I---EKAEVDNKTK  
RGR_xenTro  .LL..Y.IR.....SN  D...Q.....K.H.ST...  .QSIY..MK...QIRF..SM.VKS  ..NYRG....Y.TG..L---EKAETDNKTK  
RGR_xenLae  .LL..Y.IR.....SN  D...Q.....K.H.GT...  .QSIY..MK...QIRL..SM.VKS  ..NYRG...LY.TG..L---EKAETDSRTK  
RGR1_danRe  .VIA.L.IR.....SN  D...Q....TK.Q.S..IT  .QSIDK.FK.T.QAKF.CGT.LK.  ..NYRG....L.TG..I---ESPAIENKSK  
RGR1_pimPr  .VVA.L.IR.....SN  D...Q....TK.Q.S..IT  .QSI.R.FQ...QAKF.CST.LK.  ..NYRG....L.TGE.IVPQEVPQIENKSK  
RGR1_osmMo  .VVA.L.VR.....SN  D...Q....TK.Q.S..IT  .QSID..FK.TAKPKF.ART.LK.  ..NYRG....L.TGE.IVPQEVPQIENKSK  
RGR1_gadMo  ..VA...VK.....SN  D...Q....TE.Q.S...T  .QSID..FK.TAKPKF.ART.LK.  ..NYRG....L.TGE.IVPQEVPQIENKSK  
RGR1_takRu  .VVA.L.VR.....SN  D...Q....TK.Q.S..IT  .QSIAE.FK.T.NPRF.PST.LKA  ..NYRG....F.TGE.I---EAPQIENKSK  
RGR1_tetNi  .VVA.F.VR.....SN  D...Q....TK.Q.S..IT  .QSIAE.FK.T.NPRF.PNT.LKA  ..NYRG....F.TGE.I---E.PQLENKTK  
RGR1_gasAc  ..AA.L.VR.....SN  D...Q....TK.Q.S..IT  .QSIA..FK.T.NPRF.PNT.LKA  ..NYRG....L.TGE.I---DVPQIENKSK  
RGR1_oryLa  ..VA.L.VR.....SN  D...Q....TK.Q.ST.IT  .QSIA..FQ.T.NPRF.AST.LK.  ..NYRG....F.TGE.I---HVPQDDNKSK  
RGR_calMil  .LLA.Y.IK.....SN  D...QN.S..R.Q.S..IT  .QSCKS.FK.N.QVKF..G..VK.  ..NYRG....Y.TG..L---EKAETDNKTK  
RGR2_danRe  SVLA.LRVR.MQ..NN  D...Q...KQKMF.STSIT  ..AIHAYFK.TH.YRF..G..LKA  ..FYRG.V..F.TG..SADKKK  
RGR2_pimPr  SVLA.LRVR.IQ..NN  D...L...KQKMF.STSGT  .NGIYAHFK.TH.FKF..G..LKM  ..FYRG....F.TG..PADKKK  
RGR2_tetNi  S.V..LTVK.M.N.SN  D...Q....QK.F.STTLT  .DSIYKHFK.VHQHRF..SM.L.V  ..FYRG.V.HF.TGH.IVDPVL.KSK  
RGR2_hipHi  S.V..LTVK.M.N.SN  D...Q....QK.F.STTLT  .DSIYKHFK.VHQHRF..SM.L.V  ..FYRG.V.HF.TGH.IVDPVL.KSK  
RGR2_gasAc  S.A..LRVK.MWN.SN  D...Q....QK.F.STTLT  .DAIHKHFK.IHLHKF..ST.L.V  ..FYRG.V.HF.TG..MVDPVV.KSK  
RGR2_oryLa  S.LA.LRVK.M.S.SS  D...Q....QK.F.STSIT  .DAIYKHFK.IHYYRF..S..L.V  ..FYRG.V.NF.TG..IVEPDV.KSKQK  
RGR2_gadMo  ..VAYLRVK.M...SN  D...Q....QK.F.STT.T  .DAINKHFR.IHLQKF..K..LSV  ..SYRS.V.HF.TG..FVEPSF.KIK  
RGR2_oncMy  S.LAYISVKQM...SN  D...Q.V.NQK.F.ST.WT  .DAIHAYFK.IHKHRW..SI.L.V  ..FYRG.V..F.TG..FTEPVVVKLKGR  
RGR2_esoLu  S.LA.VSVKQM...SN  D...Q.V.NQK.F.ST.WT  .DAIHAYFK.IHKHRW..SI.L.V  ..FYRG.V..F.TG..FTEPVVVKLKGR

Select sequences are aligned relative to shark with lamprey fragment shown. The species are aligned in phylogenetic order so ancestral jawed vertebrate sequence can be deduced.

RGR_petMar                            A.L.FV.C.....T.LCVSDA....H..LLN.S.A.L.VCS......M.....----------------------------------------GA.TR..T.LCLCAWT.LSS...A....V...R......HS.......QA.G                                                                                                                               
RGR_calMil  MVSSYPLPEGFTDFEVFGLGTALLVEGLVGLLLNGLTLLAFYKIKELRTPSNLLITSLALSDFGISMNAFIAAFSSFLRYWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCSRSRLQWSSAITVTVFIWGIAAFWSAMPLLGWGVYDYEPLRTCCTLDYSKGDRNFISFFIIMGSFEFIFPIFIMLSSYQSCKSKFKKNGQVKFNTGLPVKTLIFCWGPYSLLCFYATIENITILSPKLRMIPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKL---EKAETDNKTK
RGR_xenTro  ..T.........ET...AI..T....A.L..........S....R........F.I...VA.T.LCL...V..................I...Q..VA..S..GS...........Y.T..K.H..T.VS.VF....FS........F...E....................Y..YLFT.AF...LV.L..LMTA...IYQ.M..S..IR...SM...S.V......C......V.QDA..............................................---..........
RGR_xenLae  ..T.........ET...AI..T..I.A.L..........S....R........F.I...VA.T.LCL...V..................I...Q..VA..S..GS...........Y.T..K.H.GT.VSMVL.V..FS........F...E.....................T..LFT.AF...LV.V..L.TA...IYQ.M..S..IRL..SM...S.V......C......V.QDA.........M......I.....................L.......---......SR..
RGR1_gasAc  ........D.....D..S..SC......L.I...AV.IA..L.VR.......F.VF...VA.I......T...............D.......Q..VT.....HFI..........Y.T.TK........LA..V.LFT........I...E..............T.....YV.YL.P.AI.NMAIQV.VVM.....IAQ....T.NPR..PNT.L.AML......GI.A...AV..A.LV.T....MAPI......TF.VFL.A............L...E.I---DVPQIE..S.
RGR1_tetNi  ...........S..D..S..SC......L.FF..AV.VV..F.VR.......F.VF...MA.M......TV......................Q..VT.....HFV..........Y.T.TK........LA....LFC........I...E....................YV.YLVP.AI.NMVIQV.VVM.....IAE....T.NPR..PNT.L.AMLL.....GI.A...AV..ANLV......MAPI....C.T..VFL.A............F...E.I---.TPQLE....
RGR1_danRe  ..T........SE.D..S..SC......L.FF..AV.VI..L..R.......F.VF...MA.M...T..TV..............D.......Q..MT.....HFI..........Y.T.TK........LVL.T.LFT...A....F...E....................YV.YL.P.SI.NMGIQV.VV......IDK....T..A...C.T.L..ML......GI.A...AV..A.LV.......API......TF.VF..A............L.....I---.SPAIE..S.
RGR1_oryLa  .AT........SE.D..S..SC......L.IF..SV.IV..L.VR.......F.VF...MA.I......T...........................T.....HFI..........Y.T.TK....T...LA.LV.IFT...A....I...E.............I......YV.YV.P.SI.NMGIQV.VVM.....IAQ..Q.T.NPR..AST.L...L......GI.A...AVADANLV...I...API......TF.PLL.A............F...E.I---HVPQD...S.
RGR_anoCar  ..TA..V......L...VI.......A.L.FS..M..IVS.W........G.F.VFN.....C..CF..................D...I.......T..T..SSA..V....H..Y.TGNK...G.V.PM.I.L.LFSG..A........E..............T.....Y.TYL.PLAL.H.MI.G....TA..AIDH....T..F.........S.VI......F.....AV.SV.FI...IL....VI..S...A..LI.A......Q.....F.....I---....V.....
RGR_galGal  ..T.H.......EI...AI.......A.L.FC.....IIS.R............VL.I..A.C..CI......................I...Q...T.....SSS..V......HY.T..K....T..SMM..A.LF....AT.......E....................Y.T.LFALSI.N.MI.G...MTA...IHQ....S.HY.......L...VI.....C..S...A...VMFI...Y.....II...V.T.DSF..A............F.....I---....V.S...
RGR_taeGut  ..TAH.......EI...AI.......A.L.FC.....IIS.R............VL.I..A.C..CI..................D...I...Q...T.....GSS.........HY.T.......T.VSMM..A.LF.....V.......K....................YVT.LFALST.N.MI.G...MTA...IHQ..R.T.HF.......L...VI.....C...T..AV..VMFIP..Y......I...V.T.D.FI.A............F.....I---....V.....
RGR_ornAna  ..T.H.......EI...AI.......A.L..C.....IAS.R............VV....A.S..CL..LM..L.....H....A...RL...Q..AT.....SLS...G....LRH....KP..GT.VSTVL.A..FS....M..I....Q.....................TTYLFAVAF.N.VI.L....T....IEQR...S.LF.L..R..TR..L......A.......V..V.FI..........I...V.VID.FT.A.R..D.......F.....I---.RV.VE..I.
RGR_loxAfr  .AEPGH..A..QEL..LTV..V..L.A.S..S.....I.S.C..P.....GH..VL....A.S...L..LV..M..LR.R.....D...A...Q..VT.....CS......E...HY.T....A....SALVL.V.LSS...A.L......R.N....G........R....ST..LLT.AF.N.LL.L..T.T..RLMEQ.L..K.PLQV..T..AR..LLG....A..YLC.AATDM.SI..R.Q.V...V..AV.VI..CH.A..S.VV........SR.RGESPLR.RDRTH  
RGR_choHof  .AE.RV..T..GEL..LAV.IV....A.S..T......FS.C.TP..QR..H..VL....A.S.V.L..LL..TA.LIGR..H..DS..A.S.Q..AT.....SSS.....E..RHH.TG.Q.S..T.GSLVLCV.LSSV..ATL.I....H......G.....G..R........LVTLAL.N.FL.LL...T..RLMAQ.L.RS.H.QVS.A..GRL.LLG....A..YL..AVADA.S...R.Q.V...I...M.TI..FQ.A..S.TVCRD...C.PRLRSMGRSSGHD     
RGR_homSap  .AETSA..T..GEL..LAV.MV....A.S..S..T..IFS.C.TP.....CH..VL....A.S...L..LV..T..L..R.....D...A...Q..VT.....CSS.....G...HY.T..Q.A.N..VSLVL.V.LSS...A.L......H......G..............T..LFT.SF.N.AM.L..TIT..SLMEQ.LG.S.HLQV..T..AR..LLG....AI.YL..V.ADV.SI....Q.V...I..MV.TI..IN.A....MVCR....C.SP..REKDRTK       
RGR_macMul  .AETSA..T..GEL..LAV.MV....A.S..S..T..IFS.C.TP.....CH..VL....A.S...L..L...T..L..R.....D...A...Q..VT.....CSS.....G...HY.T..Q.A.N...SLVL.V.LSST..A.L......H......G..............T..LFT.SF.N.AM.L..TIT..SLMEQ.LG.S.HLQV..T..AR..LLG....AI.YL..V.ADV.SI....Q.V...I..MV.TI..IN.A....MVCR....C.SP..SEKDRAK       
RGR_otoGar  .AEPGT..A..GEI..LAV..V....A.S..S..S..IFS.C.TP.....CH..VL....A.S...L..L.G.T..L..R.....G...A...Q..TT.....CGS.....G...HY.TGRP.A..T..SLVL.V.LSS...A.L......H...............R.....T..LFT.AF.N.LT.L..T.T...LMEQ.LRRS.HLQV..T..AR..LLG....A..YL....ADV.SI....Q.V...I...V.TI..VN.A..S.MVCR....C.SL.RSKQDGAK       
RGR_oryCun  .AEPGT..P..EEL..LAV..V....A.S..S.....IFS.C.TP..W...H..VL...VA.S...L..L...V..L..R.....D...A...Q..AT.....CGS.....G...HY.TG.Q.A.NT.VLLVL.V.LSSV..A.L......H......G........R........L.T.AF.N.LM.L..T.T..SLMEQ.LS.S.RLQV..T..GR..L......AV.YLC.AVADMSSITL..Q.V...I...V.T...VN.A..S.VI.R....C.LP.RSVRGRAQ       
RGR_musMus  .AATRA..A.LGEL..LAV..V..M.A.S.IS.....IFS.C.TPD........VL....A.T...L..LV..V..L..R..H......V...Q..AT.....CGS..V..G...HY.TGRQ.A.DT..PLVL.V.MSS...ASL..M...H.....VG........R........LFT.AF.N.LV.L..THT..RFMEQ..SRS.HLPV..T..GRM.LLG....A..YL..A.ADVSFI....Q.V...I...M.TI..IN.A.HR.MVCR.T..C.SP..SKKDRTQ       
RGR_bosTau  .AE.GT..T..GEL..LAV..V....A.S..S..I..I.S.C.TP......H..VL....A.S...L..LV..T..L..R.........A...Q..VT.....CSS..V..G...HF.TG...D.NT.VSLVF.V.LSS...A.L......H......G........R.....T..LFT.AF.N.LL.L..TVV..RLMEQ.LG.TSRPPV..V..AR..LLG....A..YL....ADA.SI....Q.V...I..AV.T...MN.A..S.MVHR....C.SP.RREHSREQ       
RGR_equCab  .AE.GS..T..REL..LAV..V....A.A..S..S..I.S.C.TP......H..VL...VA.S.L.L..LV..T..L..R.........A...Q..VT.....CSS.....G...HY.T....A.NT.VFLVF.V.LSST..A.L......H......G..............T..LLT.AF.NLLL.LL.T.T..RLMEQ.LG.T..LQV..T..AR..LL.....A..YL...VADA.SI......V...V...V.TI..VN.A..S.MLHR....C.SP..SERDRAQ       
RGR_canFam  .AD.GA..A..GEL..LAV..V....A.T..C.....I.S.C.TP.....TH..VL...VA.T...L..LV..I..L..R....PD...A...Q..AT.....CSS..L..G...HY.T.GQ.A.NT..SLVLCV.LSSV..A.L......R......G........RV....T.YLFT.AF.N.FL.LL.T.V..RLMEQ.L..P.HLQVS.TV.AR..LL.....A..YL...VADVRSVP...Q.V...I..AA.TI..IH.A..GDMVH..L..C.SP.RSQPDRAR

The terminus of RGR aligned from 47 available vertebrate sequences showing GRY ERY and DRY species:

             GPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGK (rhodopsin)           
RGR_homSap  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKREKDRTK       
RGR_panTro  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRTK   
RGR_gorGor  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSKKDRTK
RGR_ponPyg  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRTK       
RGR_macMul  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_papHam  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_nomLeu  SPKLQMVPALIAKMV PTINAVNY ALGNEMVCRGIWQCLSPQKSEKDRAK       
RGR_calJac  SPKLQMVPALIAKMV PTIDAINY ALGNEMICRGIWQCLSPQKSEKDRTK   
RGR_tarSyr  SPKLQMVPALIAKTV PTINAYHY ALGSEMVCRGIWQCLSPHSSEHHRAK
RGR_otoGar  SPKLQMVPALIAKTV PTINAVNY ALGSEMVCRGIWQCLSLQRSKQDGAK       
RGR_micMur  SPKLQMVPALIAKTV PTINAINY ALGSETVCRGIWQCLSPQRSEQDRAK       
RGR_tupBel  SPKLQMVPALVAKMV PTVNAVNY ALGSETICRGIWGCLSP KRERDRAR      
RGR_musMus  SPKLQMVPALIAKTM PTINAINY ALHREMVCRGTWQCLSPQKSKKDRTQ       
RGR_ratNor  SPKLQMVPALIAKTM PTINAINY ALRSEMVCRGTWQCRSAQKSKQDRTQ       
RGR_dipOrd  SPKLQMVPALIAKMV PTVNAINY ALCNELLCGGFSLGLLPQKGKQDRTQ       
RGR_cavPor  SPRLQMVPALIAKTV PTINAINY SLGsevirRGPWQSLEMQRSKQDRT    
RGR_oryCun  TLKLQMVPALIAKTV PTVNAVNY ALGSEVIRRGIWQCLLPQRSVRGRAQ       
RGR_ochPri  SPKLLMVPALIAKAV PTVNAINY ALGSEVIRRGIWQCLLPQRSVRDRAQ           
RGR_bosTau  SPKLQMVPALIAKAV PTVNAMNY ALGSEMVHRGIWQCLSPQRREHSREQ       
RGR_susScr  SPKLQMVPALIAKMV PTVNAINY ALGGEMVHRGIWQCLSPQRRERDREQ       
RGR_equCab  SPKLRMVPALVAKTV PTINAVNY ALGSEMLHRGIWQCLSPQKSERDRAQ       
RGR_myoLuc  PPRLQVVPALIAKMV PTVNAVNY ALGSemvqrGIWQRLSLQrSGWDSAQ
RGR_pteVam  SPKLQMVPALIAKMA PTINAVNY ALGSEMVQRGIWQCLSPQRSERDHAQ       
RGR_canFam  PPKLQMVPALIAKAA PTINAIHY ALGGDMVHGGLWQCLSPQRSQPDRAR       
RGR_felCat  SPKLQMVpaliakaV PTINAINY ALGSEMVHRGIWQCLSPQGSGLDRAR
RGR_eriEur  SPKLQMVPALIA MV PTVNAVHY VLGSEKVHKGFWQCFSPQRSEQDRAR     
RGR_sorAra  spklqMVPALIAKTV PTVNALHY GLGS       
RGR_loxAfr  SPRLQMVPALVAKAV PVINACHY ALGSEVVRGGIWQYLSRQRGESPLRARDRTH  
RGR_echTel  SPKLQMVPAIVAKAV PIVNACHY ALGNKVLRRGIWQFLSQQSGR PLSSQDRTQ
RGR_proCap  SPKLQMVPALIAKAV PIVNACHY ALGSETVHRGIWQCLSRQRGESPPRTRDRTQ  
RGR_choHof  sprlqMVPALIAKTM PTINAFQY ALGSETVCRDIWQCLPRLRSMGRSSGHD   
RGR_dasNov  SPRLQMVPALIAKTM PTVNALYY ALGRESVHRNAwQLLRGGGAMAAQHA                      
RGR_ornAna  SPKLRMIPALIAKTV PVIDAFTY ALRNEDYRGGIWQFLTGQKIERVEVENKIK
RGR_anoCar  SPKILMIPAVIAKSS PAANALIY ALGNENYQGGIWQFLTGQKIEKAEVDNKTK
RGR_galGal  SPKYRMIPAIIAKTV PTVDSFVY ALGNENYRGGIWQFLTGQKIEKAEVDSKTK
RGR_taeGut  PPKYRMIPALIAKTV PTVDAFIY ALGNENYRGGIWQFLTGQKIEKAEVDNKTK
RGR_xenTro  SPKLRMIPALLAKTS PAVNAYVY GLGNENYRGGIWQYLTGQKLEKAETDNKTK
RGR_xenLae  SPKLRMMPALLAKIS PAVNAYVY GLGNENYRGGIWLYLTGQKLEKAETDSRTK
RGR_danRer  SPKLRMIAPILAKTS PTFNVFVY ALGNENYRGGIWQLLTGQKIESPAIENKSK
RGR_takRub  SPKLRMMAPILAKTC PTINVFLY ALGNENYRGGIWQFLTGEKIEAPQIENKSK
RGR_tetNig  SPKLRMMAPILAKTC PTVNVFLY ALGNENYRGGIWQFLTGEKIETPQLENKTK
RGR_gasAcu  STKLRMMAPILAKTS PTFNVFLY ALGNENYRGGIWQLLTGEKIDVPQIENKSK
RGR_oryLat  SPKIRMIAPILAKTS PTFNPLLY ALGNENYRGGIWQFLTGEKIHVPQDDNKSK
RGR_gadMor  SPKLRMMAPILAKTA PTFNVFLY ALGNENYRGGIWQLLTGEKIEVPQIENKSK
RGR_hipHip  SPKLRMILPVLAKTN PIFNALLY SFGNEFYRGGVWHFLTGQKI VDPVVKKSK
RGR_oncMyk  SPKLRMLLPVLAKTN PIFNAWLY SFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR
RGR_pimPro  SPKLRMVLPVLAKTS PIFHAAMY AYGNEFYRGGIWQFLTGQK     PADKKK     
             GPIFMTIPAFFAKSA AIYNPVIY IMMNKQFRNCMLTTICCGK (rhodopsin)

RGR signaling in olfactory bulb and retinal pigmented epithelium

RGR opsins in GRY mammals could signal through a heterotrimeric G protein. However from the alignments below, it can be seen that the critical YR portion of the heterotrimeric Galpha binding motif conformational switch is missing in the GRY mammals. This would not affect photoreceptive spectrum but might impact binding or release of substrate. Consequently these opsins will not be able to signal through binding to a Galpha protein. Lacking coupling, such RGR are still opsins but not GPCR.

However, the shift to GRY is boreoeutheres is not satisfactorily described as loss of function because the G itself is invariant over a 1.4 billion years of branch length. Thus it represents an innovation under strong selective pressure whose adaptiveness is not yet understood.

On the flip side, the ERY mammals and DRY vertebrates do seem to have retained a satisfactory switch region (the NYRG region that stands out in the difference alignment below). This suggests ancestral signaling capability has continued to the present day in these species. However it cannot be assumed that signaling takes place in every cell type in which the gene is expressed because significant signaling in only one cell type would assure conservation of the necessary features.

Which of the 16 vertebrate paralogs of Galpha do these DRY RGR use for signaling? In theory, any RGR in any given species could be threaded to a known 3D structure and computationally docked to each of the similarly modeled Galpha subunits of that species, the most favorable fit then being the prediction. That might not be feasible if the responsible region is a cytoplasmic loop not effectively predicted by the 7-transmembrane constraint. More than one binding partner might be possible given that the Galpha are all duplicates of a single ancestral gene whose 3D structure has not changed substantially.

Alternatively, seeking primary sequence correlations from comparative genomics, requires extensive seeding from experimentally known opsin/Galpha binding pairs as classified in an Oct 2008 cnidarian opsin study. This is not ab initio prediction so much as homology transfer across orthology classes to opsins lacking direct experimental data. Here, RGR has only distant sequence and exon boundary affinities to ciliary imaging opsins with known Galpha partners.

The purpose served by photoreceptive signaling in the RPE is equally unclear. Signaling capacity may only be important in other cell types -- the Allen brain atlas in mice provides a high resolution sagittal section showing significant RGR expression in the main olfactory bulb and olfactory nerve layer. RRH (peropsin) is also expressed very similarly in mouse olfactory as well in cerebellar cortex. Expression chips show mouse RGR transcribed in liver, iris, eyecup, ciliary body, and lacrimal gland in addition to retina and RPE. However all the many dozen GenBank mouse transcripts of RGR originate from RPE/choroid or retina, probably because of library bias.

Retinal expression of chicken RGR occurs in the inner nuclear layer (INL) and ganglion cell layer (GCL) along with RRH; RPE expression could not be studied by the method used. Pineal gland RGR and RRH are expressed in a light-entrained daily cycle though again not exactly colocalized. Chicken embryonic GCL are also known to express melanopsin and Gq transducin (but not ciliary Gt). Three opsins in the same cell complicates the search for a signaling partner specific to RGR.

One intriguing possibility (assuming RGR expression in mouse olfactory node has counterparts in D/ERY vertebrates) is Golf (Gs) signaling via type 3 adenylyl cyclase in which elevated cAMP activates CNG membrane conductance channels. While the massive loss of olfactory genes in primates has similar timing to the advent of GRY it leaves mouse olfaction uncorrelated. Mouse of course is also a boreoeuthere.

Local splice migration and exon-skipping in RGR opsins

RGR in primates may contain an earlier splice acceptor in the second intron resulting in insertion of four amino acids in the extracellular loop EX1 between TM2 and TM3. This is observed in a number of human transcripts but all appear to originate from a single brain tumor sample (eg BC011349). The intronic region is conserved in the UCSC 28-way track but it cannot be a splice acceptor in tarsier, mouse lemur, or tree shrew much less other placentals. For example, in dog, horse and armadillo, translation would cause loss of reading frame -- and horse even has the AG acceptor. Thus it is difficult to say whether the insert is simply tolerated or has acquired a secondary function. The nucleotide sequence might be conserved as part of a splice enhancer.

A second defective splice isoform has also been studied that entirely skips the 6th exon. While exons don't correspond cleanly to transmembrane domains, nevertheless TM7 is lost -- while the altered protein has been proven to be produced abundantly by mass spectroscopy (unlike the vast majority of supposed alternative splices), it cannot function as an opsin.

In fact it accumulates extra-cellularly at the basal boundary of RPE cells primarily in Bruch's membrane, adjacent choriocapillaris, and intercapillary region. The carboxy terminus has been cleaved as well. A role in degenerative eye disease has neither been established nor ruled out.

Exon-skipping cannot produce viable product in any opsin, the reason being for an internal exon it would have to consist exactly of a complete triplet of transmembrane, extracellular and intracellular domains so as not to perturb the localization pattern. No opsin is intronated in this way. Terminal skipping would omit the critical FR region in all opsins.

Thus exon-skipping in opsins and other GPCR, rather than a source of functional innovation, is really a test bed for studying transcription error (and experimental artifact), primarily with implications for sub-clinical disease.

Possibilities for upstream splice migration in Euarchonta:

>RGR_ext_homSap VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGTTATCACCACTACTGCACCCGT
>RGR_ext_panTro VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_gorGor VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_ponPyg VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGTTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCGTGGGGGCGCTATCACCACTACTGCACCCGT 
>RGR_ext_nomLeu VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCATTAGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_macMul VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCTATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_papHam VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCAGATGGCTGCCAGGCTCATGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCTATCGCCTGGGGGCGCTATCATCACTACTGCACCCGT
>RGR_ext_calJac VSHRRWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGATTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCGGCAGTGCAGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_tarSyr
GGTGTCTCCCACAGGCGCTGGCCGTACGGCTTGGACGGCTGCCAGGCTCACGGCTTCCAAGGCTTTGTGACAGCTTTGGCCAGCATCGGCGGCAGCGCAGCCATCGCCTGGGGGCGCTATCATCACTACTGCACTCGT
>RGR_ext_otoGar VLHRRWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCTR
AGTGTTCTCCACAGGCGCTGGCCCTACGGCTCAGGTGGCTGCCAGGCTCACGGCTTCCAGGGCTTCACGACGGCATTGGCCAGCATCTGCGGCAGCGCAGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_micMur
CGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGATGGCTGCCAGGCTCACGGCTTCCAGGCTGCGTGACGGTGCTGGCCAGCATCTGCAGCAGCGCGGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_tupBel
CATGTCTTCCACAGGCGCTGGCCCTACGGCTCAGACGGCTGCAAGGTTCATGGCTTCCAGGGCTTCGCAACAGCGTTGGCCAGCATCTCTGGCAGCGCGGCCATCGCCTGGGGGCGCTATCACCAGTACTGCACTCGT

RGR curated reference sequences

Clear orthologs are easily collected back to lamprey. In low x genome projects, the trace archives sometimes have to be consulted at anomalous residues. GenBank sequences contain many errors and erroneous interpretations of splice artifacts and cannot be used at face value. No amphioxus counterpart can be found as of the second genome assembly. Ciona retained two distantly related genes of the ancient RGR swarm but echinoderms did not. No trace of the gene can be found in earlier diverging invertebrates, even though the gene must have originated very early in metazoans.

RGR reference sequences from 51 vertebrates

>RGR_homSap Homo sapiens (human) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKREKDRTK* 0

>RGR_panTro Pan troglodytes (chimp) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAIPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK* 0

>RGR_gorGor Gorilla gorilla (gorilla) 0 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLAPAESGISLNALVGATSTLLG 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSTLACKSAVSLVLSGRMSSAFWADLPLLGWGPYDYEPLRTCCTLDYSEADR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSKKDRTK* 0

>RGR_ponPyg Pongo pygmaeus (orang_abelii) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAVLYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK * 0

>RGR_nomLeu Nomascus leucogenys (gibbon) 
0 MAETSVLPTGFGELKLLAGGMGLLAE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAVNYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_macMul Macaca mulatta (rhesus) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_papHam Papio hamadryas (baboon) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_calJac Callithrix jacchus (marmoset) 
0 MAESSTLPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSTFWAAFPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTIDAINYALGNEMICRGIWQCLSPQKSEKDRTK* 0

>RGR_tarSyr Tarsius syrichta (tarsier) 
0 MAEAGALPAGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLR 2
1 RWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCT 1
2 GSQLAWNTAISLVLFVWLSYAFWAALPLLGWGHYDYEPLGTCCTLEYSKGDR 2
1 0
0 VNTTLPIRTLMLGWGPYALLYLCAVIADVTSISPKLQM 0
0 VPALIAKTVPTINAYHYALGSEMVCRGIWQCLSPHSSE* 0

>RGR_otoGar Otolemur garnettii (bushbaby) 
0 MAEPGTLPAGFGEIEVLAVGTVLLVE 1
2 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GRPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYDYEPLRTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLTPLFITLTSYQLMEQKLRRSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATIADVTSISPKLQM 0
0 VPALIAKTVPTINAVNYALGSEMVCRGIWQCLSLQRSKQDGAK* 0

>RGR_micMur Microcebus murinus (mouse_lemur) 
0 MAEPGTLPTGFRELEVLAVGTVLLVE 1
2 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NVTSFLFTMAFFNFLIPLFITHTSYQLMEQKLKKSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATVADVTSISPKLQM 0
0 VPALIAKTVPTINAINYALGSETVCRGIWQCLSPQRSEQDRAK* 0

>RGR_tupBel Tupaia belangeri (treeshrew) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTVFSFCKSPELRTPSHLLVLSVALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCT 1
2 2
1 NFTSFLFTMAFFNFLMPLFITLTSYWLMEEKLRKGGRLQ 0
0 VNTTLPSRTLLLGWGPYALLYLYAAFADVTPLSPKLQM 0
0 VPALVAKMVPTVNAVNYALGSETICRGIWGCLSPKRERDRAR* 0

>RGR_musMus Mus musculus (mouse) 
0 MAATRALPAGLGELEVLAVGTVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLP 0
0 VNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALHREMVCRGTWQCLSPQKSKKDRTQ* 0

>RGR_ratNor Rattus norvegicus (rat) 
0 MTATRALPAGFGELEVLAIGIVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWLSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKLSRSGHLQ 0
0 VNTTLPGRMLLLGWGPYALLYLYAAVADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALRSEMVCRGTWQCRSAQKSKQDRTQ* 0

>RGR_speTri Spermophilus tridecemlineatus (ground_squirrel) 
0 MAETAALPAGFGELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELRTPNHLLLLSLAVADSGISLNALIAAISSLLR 2
1 RWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAIPLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFFVPLFITLTSYRLMEQKLARSGHLQ 0
0 0
0 * 0

>RGR_dipOrd Dipodomys ordii (kangaroo_rat) 
0 MATSGDLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPIHLLDLSLAVADSGISLNALIAAISSLEW 2
1 HWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCT 1
2 GSLLGWDTAVSLVIFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLVPLFITLTSYQLMKQKFARSGRLQ 0
0 VNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQM 0
0 VPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ* 0

>RGR_cavPor Cavia porcellus (guinea_pig) 
0 MATSEALPAGFGELEVLAVGTVLLLE 1
2 GLCGLSLNGLTVVSFWKSPALRTPNHLLVLSLALADSGLSLNALVAAGSSLLR 2
1 HWPGSGHCQALGFQGFTTALASISGTAALSWGRHQQCCT 1
2 RGRLTWSTAVPLVLFVWLSSAFWAALPLLGWGRYDYEPLGTCCTLDYSTGDR 2
1 NFTSFLFTMAFFNFLVPLFITVTSCQLMERHLARSSRLQ 0
0 VSVRQPARTLLLCWSPYALLYLYAVLADAHTLSPRLQM 0
0 VPALIAKTVPTIYSLGRGPWQSLEMQRSKQD* 0

>RGR_oryCun Oryctolagus cuniculus (rabbit) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELWTPSHLLVLSLAVADSGISLNALIAAVSSLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLITMAFFNFLMPLFITLTSYSLMEQKLSKSGRLQ 0
0 VNTTLPGRTLLFCWGPYAVLYLCAAVADMSSITLKLQM 0
0 VPALIAKTVPTVNAVNYALGSEVIRRGIWQCLLPQRSVRGRAQ* 0

>RGR_ochPri Ochotona princeps (pika) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTMAFFNFLMPLFIMLTSYSLMEQKLAKSGRLQ 0
0 VNTTLPARTLLFCWGPYAILCLCATVMDMSTVSPKLLM 0
0 VPALIAKAVPTVNAINYALGSEVIRRGIWQCLLPQRSVRDRAQ* 0

>RGR_canFam Canis familiaris (dog) 
0 MADSGALPAGFGELEVLAVGTVLLVE 1
2 ALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLR 2
1 RWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCT 1
2 RGQLAWNTAISLVLCVWLSSVFWAALPLLGWGRYDYEPLGTCCTLDYSRVDR 2
1 NFTSYLFTMAFFNFFLPLLITLVSYRLMEQKLKKPGHLQ 0
0 VSTTVPARTLLLCWGPYALLYLYATVADVRSVPPKLQM 0
0 VPALIAKAAPTINAIHYALGGDMVHGGLWQCLSPQRSQPDRAR* 0

>RGR_felCat Felis catus (cat) 
0 MAESGSLPTGFGELEVLAVGMVLLVE 1
2 2
1 RWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCS 1
2 GSQLAWNTAISLVICVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFFMPLFITFISYRLMEQKLRKTGHLQ 0
0 VNTTLPARTLLFGWGPYALLYLYATIADVSSVSPKLQM 0
0 VPTINAINYALGSEMVHRGIWQCLSPQGSGLDRAR* 0

>RGR_ailMel Ailuropoda melanoleuca (panda) XM_002915389
0 MAGSGSLPTGFGELEVLAVGTVLLVE 1
2 ALAGLCLNSLTILSFCKTPELRTPTHLLVLSLALADTGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFIASLASICSSAAIAWGRYHHYCT 1
2 RRQLAWNTAISLVICVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRVDR 2
1 NFTSFLFTMAFFNFFLPLFITLVSYRLMEQKLRKTGHLQ 0
0 VNTTLPARTLLFGWGPYALLYLYTTVADVSSISPRLQM 0
0 VPALIAKTVPTINAINYALGSEMVHRGIWQCLSLQRSELDRAR* 0

>RGR_bosTau Bos taurus (cow) 
0 MAESGTLPTGFGELEVLAVGTVLLVE 1
2 ALSGLSLNILTILSFCKTPELRTPSHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLLPLFITVVSYRLMEQKLGKTSRPP 0
0 VNTVLPARTLLLGWGPYALLYLYATIADATSISPKLQM 0
0 VPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ* 0

>RGR_turTru Tursiops truncatus (dolphin) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTILCFCKNPELRTPSHLLVLSLALSDSGISLNALMAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWATLPLLGWGHYDREPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFLLPLFITVISYRLMEQKLGKTGRPP 0
0 VNTVLPARTLLFGWGPYALLYLYAAVADVTSISPKLQM 0
0 * 0

>RGR_susScr Sus scrofa (pig) 
0 MAEPGALPTGFGELEVLAVGTLLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPSHLLVLSLALADSGISLNAFVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 RSRLDWNTAVSLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRVDR 2
1 NFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPP 0
0 VNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQM 0
0 VPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ* 0

>RGR_vicVic Vicugna vicugna (vicugna) 
0 MAESRALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPNHLLVLSLALADSGISLNALVAATSSLLR 2
1 1
2 GSRLDWNTAVSLVFFVWLSSTCWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 0
0 0
0 * 0

>RGR_equCab Equus caballus (horse) 
0 MAESGSLPTGFRELEVLAVGTVLLVE 1
2 ALAGLSLNSLTILSFCKTPELRTPSHLLVLSLAVADSGLSLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSRLAWNTAVFLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLLTMAFFNLLLPLLITLTSYRLMEQKLGKTGQLQ 0
0 VNTTLPARTLLLCWGPYALLYLYATVADATSISPKLRM 0
0 VPALVAKTVPTINAVNYALGSEMLHRGIWQCLSPQKSERDRAQ* 0

>RGR_myoLuc Myotis lucifugus (microbat) 
0 MAEAGSLPTGFGELEVLAVGVVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCT 1
2 GSRLAWRTAASLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCSLGYARGSR 2
1 NFTSFLFLMAFFNFLLPLFITFTSYRLMEQKLGRTRPPQ 0
0 VNTTLPARTLLLGWGPYALLHLCAALAGTALIPPRLQV 0
0 VPALIAKMVPTVNAVNYALGSGIWQRLSLQ* 0

>RGR_pteVam Pteropus vampyrus (macrobat) 
0 MAESRSLPTVFWELEVLAVGTVLMVE 1
2 ALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GSRLAWNTAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFVLPLFITLTSYQLMEQKLGKTGHPQ 0
0 VNTTLPARTLMLCWGPYALLYLYAAVMDVASISPKLQM 0
0 VPALIAKMAPTINAVNYALGSEMVQRGIWQCLSPQRSERDHAQ* 0

>RGR_sorAra Sorex araneus (shrew) 
0 MTESGALPAGFKELKMLAVGTLLLWG 1
2 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GRQLAWDVAIALVIFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGGR 2
1 NFVSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKMGQPQ 0
0 0
0 VPALIAKTVPTVNALHYGLGSGMVQNGFRKGLWLQRRERERAL* 0

>RGR_eriEur Erinaceus europaeus (hedgehog) 
0 1
2 2
1 RWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCT 1
2 RSRLAWNTAVFLVFFVWVSSVFWAALPLLGWGHYDYEPLGTCCTLDYSSGDR 2
1 NFISFLFTMAFFNFLLPLFITLISYQLMEQKLRKTGHPQ 0
0 VNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQM 0
0 VPALIAMVPTVNAVHYVLGSEKVHKGFWQCFSPQRSEQDRAR* 0

>RGR_loxAfr Loxodonta africana (elephant) 
0 MAEPGHLPAGFQELEVLTVGTVLLLE 1
2 ALSGLSLNGLTILSFCKIPELRTPGHLLVLSLALADSGISLNALVAAMSSLRR 2
1 RWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCT 1
2 RSRLAWSSASALVLFVWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLLTMAFFNFLLPLFITLTSYRLMEQKLKKKGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLCAAATDMTSISPRLQM 0
0 VPALVAKAVPVINACHYALGSEVVRGGIWQYLSRQRGESPLRARDRTH* 0

>RGR_proCap Procavia capensis (hyrax) 
0 MADPRPLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRG 2
1 RWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCT 1
2 GSKLAWSSAGALVLFMWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLFTMAFFNFLLPLFITLASYRLMEQKLKKEGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLYTAITDVNSISPKLQM 0
0 VPALIAKAVPIVNACHYALGSETVHRGIWQCLSRQRGESPPRTRDRTQ* 0

>RGR_echTel Echinops telfairi (tenrec) 
0 MVEPRTLPPGFGELEVLAVGTVLLVE 1
2 2
1 HWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCT 1
2 GSQFTWSSASTLVLFMWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMTFFNFSMPILVTLTSYQLMQQKLKKSGPLQ 0
0 VNTTLPTRTLLLGWGPYALLYLCAACTDVTGISPKLQM 0
0 VPALIAKAVPIVNACHYALGSETVHRGIWQCLSRQRGESPPRTRDRTQ* 0

>RGR_dasNov Dasypus novemcinctus (armadillo) 
0 MAGSGVLPPGFGELEVLAVGTVLLVE 1
2 ALSGLVLNGLAIISFCKTPELRSPSRLLVLSLALADSGVSLNALVAATSSLLR 2
1 RWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCI 1
2 GRRLAWSTAGCLVLCLWMAAAFWAALPLLGWGLYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQ 0
0 VSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQM 0
0 VPALIAKTMPTVNALYYALGRESVHRNA* 0

>RGR_choHof Choloepus hoffmanni (sloth) 
0 MAESRVLPTGFGELEVLAVGIVLLVE 1
2 ALSGLTLNGLTLFSFCKTPELQRPSHLLVLSLALADSGVSLNALLAATASLIG 2
1 RWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCT 1
2 GSQLSWSTAGSLVLCVWLSSVFWATLPILGWGHYDYEPLGTCCTLGYSRGDR 2
1 0
0 0
0 VPALIAKTMPTINAFQYALGSETVCRDIWQCLPRLRSMGRSSGHD* 0

>RGR_ornAna Ornithorhynchus anatinus (platypus) 
0 1
2 ALLGLCLNGLTIASFRKIKELRTPSNLLVVSLALADSGICLNALMAALSSFLR 2
1 HWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCS 1
2 RSKPQWGTAVSTVLFAWGFSAFWSMMPILGWGQYDYEPLRTCCTLDYSKGDR 2
1 NFTTYLFAVAFFNFVIPLFIMLTSYQSIEQRFKKSGLFK 0
0 LNTRLPTRTLLFCWGPYALLCFYATVENVTFISPKLRM 0
0 IPALIAKTVPVIDAFTYALRNEDYRGGIWQFLTGQKIERVEVENKIK* 0

>RGR_anoCar Anolis carolinensis (lizard) 
0 MVTTAYPVPEGFTDLEVFVIGTALLVE 1
2 ALLGFSLNMLTIVSFWKIKELRTPGNFLVFNLALSDCGICFNAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCT 1
2 GNKLQWGSVIPMTIFLWLFSGFWAAMPLLGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYITYLIPLALFHFMIPGFIMLTAYQAIDHKFKKTGQFK 0
0 FNTGLPVKSLVICWGPYSFLCFYAAVESVTFISPKILM 0
0 IPAVIAKSSPAANALIYALGNENYQGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_galGal Gallus gallus (chicken) 
0 MVTSHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCT 1
2 RSKLQWSTAISMMVFAWLFAAFWATMPLLGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYITFLFALSIFNFMIPGFIMMTAYQSIHQKFKKSGHYK 0
0 FNTGLPLKTLVICWGPYCLLSFYAAIENVMFISPKYRM 0
0 IPAIIAKTVPTVDSFVYALGNENYRGGIWQFLTGQKIEKAEVDSKTK* 0

>RGR_taeGut Taeniopygia guttata (finch) 
0 MVTAHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCT 1
2 RSRLQWSTAVSMMVFAWLFAAFWSVMPLLGWGKYDYEPLRTCCTLDYSKGDR 2
1 NYVTFLFALSTFNFMIPGFIMMTAYQSIHQKFRKTGHFK 0
0 FNTGLPLKTLVICWGPYCLLCTYAAVENVMFIPPKYRM 0
0 IPALIAKTVPTVDAFIYALGNENYRGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_xenTro Xenopus tropicalis (frog) 
0 MVTSYPLPEGFTETEVFAIGTTLLVE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWSTAVSVVFFIWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYISYLFTMAFFEFLVPLFILMTAYQSIYQKMKKSGQIR 0
0 FNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 IPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKLEKAETDNKTK* 0

>RGR_xenLae Xenopus laevis (frog) NM_001092855 mRNA
0 MVTSYPLPEGFTETEVFAIGTTLLIE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWGTAVSMVLFVWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NFTSFLFTMAFFEFLVPVFILLTAYQSIYQKMKKSGQIR 0
0 LNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 MPALLAKISPAVNAYVYGLGNENYRGGIWLYLTGQKLEKAETDSRTK* 0

>RGR1_cynPyr Cynops pyrrhogaster (newt) Deut.Amph.Batr FS290827 frag G? lens regenerating iris
0  GFTEIEVFGLGTALLIE 1
2 ALLGFILNGLTLLSFYKIRSLRTPHNFLIVSLALADTGVCINAFIAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVTALSSISSCGVIAWDRYNQYCT 1
2 RTKLQWGTAISLVSFVWAFSAFWSVMPLLGWGQYDYEPLRTCCTLDYTKGDK 2
1 NFISYLFPLAFFEFVIPLFIMLTAYQSVEQKFKKTGQHK 0
0 FNTGLPVKTLVMCWGPYSLLCFYATIENATTISPKIRM 0
0 LPAILAKTAPAINAFLYGMGNESYRGGIWQFlTGQKIEKAEVDNKTK* 0

>RGR1_danRer Danio rerio (zebrafish) 
0 MVTSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVLFTWLFTAFWAAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAK 0
0 FNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 IAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKIESPAIENKSK* 0

>RGR1_takRub Takifugu rubripes (fugu) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPSTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTINVFLYALGNENYRGGIWQFLTGEKIEAPQIENKSK* 0

>RGR1_tetNig Tetraodon nigroviridis (pufferfish) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFFKVRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLVPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPNTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTVNVFLYALGNENYRGGIWQFLTGEKIETPQLENKTK* 0

>RGR1_gasAcu Gasterosteus aculeatus (stickleback) 
0 MVSSYPLPDGFTDFDVFSLGSCLLVE 1
2 GLLGILLNAVTIAAFLKVRELRTPSNFLVFSLAVADIGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFVWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYVSYLIPMAIFNMAIQVFVVMSSYQSIAQKFKKTGNPR 0
0 FNPNTPLKAMLFCWGPYGILAFYAAVENATLVSTKLRM 0
0 MAPILAKTSPTFNVFLYALGNENYRGGIWQLLTGEKIDVPQIENKSK* 0

>RGR1_oryLat Oryzias latipes (medaka) 
0 MATSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGIFLNSVTIVAFLKVRELRTPSNFLVFSLAMADIGISMNATIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSTAITLAVLVWIFTAFWAAMPLIGWGEYDYEPLRTCCTLDISKGDR 2
1 NYVSYVIPMSIFNMGIQVFVVMSSYQSIAQKFQKTGNPR 0
0 FNASTPLKTLLFCWGPYGILAFYAAVADANLVSPKIRM 0
0 IAPILAKTSPTFNPLLYALGNENYRGGIWQFLTGEKIHVPQDDNKSK* 0

>RGR1_gadMor Gadus morhua (cod) ES469757
0 MVSAYPLPEGFSDFDVFSFGSFLLVE 1
2 GLLGIILNAVTIVAFCKVKELRTPSNFLVFSLAMADIGISMNASVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCT 1
2 RTELQWSSAVTLSVFIWLFSAFWSAMPLIGWGTYDYEPLRSCCTLDYTKGDR 2
1 NYVSYLIPMTVFNMVVQIFVVMSSYQSIDQKFKKTAKPK 0
0 FNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRM 0
0 MAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK* 0

>RGR1_pimPro Pimephales promela DT198813 frag
0 MVTYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKIRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVIFIWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIERKFQKSGQAK 0
0 FNCSTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 LAPILA

>RGR1_osmMor Osmerus mordax (smelt) EL524757 frag
0 MVSSYPLPDGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISSNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVMFIWLFTAFWSAIPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMAIQIFVVLSSYQSIGEK

>RGR_calMil Callorhinchus milii (elephantfish) frag
0   EGFTDFEVFGLGTALLVE 1
2 GLVGLLLNGLTLLAFYKIKELRTPSNLLITSLALSDFGISMNAFIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCS 1
2 RSRLQWSSAITVTVFIWGIAAFWSAMPLLGWGVYDYEPLRTCCTLDYSKGDR 2
1 NFISFFIIMGSFEFIFPIFIMLSSYQSCKSKFKKNGQVK 0
0 FNTGLPVKTLIFCWGPYSLLCFYATIENITILSPKLRM 0
0 * 0

>RGR_petMar Petromyzon marinus (lamprey) frag, did not make assembly
2 ALLGFVLCGLTLLTFLCVSDARTPSHLLLLNLSLADLGVCSNAFIAAMSSFLR 2
2 GARTRWSTALCLCAWTWLSSAFWAAMPLVGWGRYDYEPLHSCCTLDYSQADG 2

>RGRa_cioInt Ciona intestinalis (tunicate) Ci-opsin3 last 4 exons match RGR unusual DKY
0 MEVNDKRVYGVLMGLL 1
2 GLLTITGYSLLFVIFAKRPDLKKKNKFLLSLATSDLLITVHVFASTIAAFAPQWPFGDLGCQ 0
0 VDAFIGMAPTFISIAGAALIAKDKYYRFCKPKM 1
2 MVGRNYSFHVYLTWTMGIIGGALPFIGFGRYGFETDDVTWRTGCLLDFKSISA 2
1 KYSFYIILISTVWFVWPVYKLVSSYMKISTKINKFYP 0
0 LLFVVPVQMAIGLLPYAIYAMVSITIGVSAVPYFCVVINN 0
0 LAAKVFVGSNPFIYIYFDPELRESCKQIFCSPPAPTNDKISEDSKDE* 0

>RGRb_cioInt Ciona intestinalis (tunicate) entire neural tube CiNut DRY
0 MEIDFGFARTVYGVALLLM 1
2 VFITLLGYAVYFGAIWRSKTLQTRHIWLTSLACGDIIMMVHLILESLSSLGMGHRPRQNFECQ 0
0 VGALVGLFSGYVTIASITWIAIDRYYRQCKPEK 1
2 VGVNYCFYVIIVWAMSFLAASGPALGFGAYESAEENTVKCLIDLNKKDT 2
1 NSRLYIILVSAVWFVYPFVKMILYNKKLVQEAKEPQP 0
0 MAFAVPLTFFLCYLPFAIYASLKITVGLPPLNSMVVASIY 0
0 MLPKVISVVNPYLYMRSDPELLAACRHVVGLTDGKKAV* 0

>RGRa_cioSav Ciona savignyi (tunicate) Ci-opsin3 68% 288 larval unusual DKY
0 MDFSSKRTYGIAMAAL 1
2 GFIAWVGYGLLFVIFAKSPDLKKKNRFLFSLAVSDLLITIHVVASVVASFQSEWPFGSIGCQ 0
0 LDAFIGMAPTFISIAGAALVAKDKYYRICKPKM 1
2 LVGRNYSFSIYANWTLGIIGGLLPFFGFGQYGFETDDLSLRTGCLLDFKTVSA 2
1 KYRFYIVFISLVWFVWPLYKLTSHYIKISAKLDRFHP 0
0 LMFVVPLQMLVSLLPYAIYAMISITVGVSSAPYYLVAVNN 0
0 IAAKVFIGTNPFIYIYFDPELRLACKNLFKYSSTPVQDQIQDKKDE* 0

RGR2 reference sequences from 9 teleost fish

>RGR2_danRer zebrafish NM_001024436 embryonic RPE, brain, gut, embryo PA indel
0 MASYPLPEGFTDFDMFAFGSALLVG 1
2 GLLGFFLNAISVLAFLRVREMQTPNNFFIFNLAVADLSLNINGLVAAYACYLR 2
1 HWPFGSEGCQLHAFQGMVSILAAISFLGAVAWDRYHQYCT 1
2 KQKMFWSTSITISCLIWILAVFWAAMPLPAIGWGVFDFEPLRTCCTLDYSQGDR 2 
1 GYITYMLTITVLYLAFPVLVLQSSYSAIHAYFKKTHHYR 0
0 FNTGLPLKALLFCWGPYVVVCSLACFEDVSVLSPRLRM 0
0 VLPVLAKTSPIFHAVLYAYGNEFYRGGVWQFLTGQKSADKKK* 0

>RGR2_pimPro Pimephales promelas liver brain PA indel
0 MASYALPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNLISVLAFLRVREIQTPNNFFIFNLAVADLSLNINGLVAAYASYLR 2
1 YWPFGSEGCQIHGFQGMVSILASISFLGAIAWDRYHLYCT 1
2 KQKMFWSTSGTISALIWILAVFWAALPLPAIGWGVFDFEPMRTCCTLDYTIGDR 2
1 NYISYMLTITVLYLAFPVLIMQSSYNGIYAHFKKTHHFK 0
0 FNTGLPLKMLLFCWGPYVLMCTYACFENASLVSPKLRM 0
0 VLPVLAKTSPIFHAAMYAYGNEFYRGGIWQFLTGQKPADKKK* 0

>RGR2_tetNig Tetraodon nigroviridis eyes
0 MAAYTLPEGFTEFDMFTFGTALLVG 1
2 GVLGFFLNAISIVSFLTVKEMRNPSNFFVFNLALADISLNVNGLIAAYASYLR 2
1 YWPFGQDGCSYHAFHGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSSIIWILSIFWSAVPLMGWGVYDFEPMRTCCTLDYTRGDR 2
1 DYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHR 0
0 FNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRM 0
0 LLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK* 0

>RGR2_gasAcu Gasterosteus aculeatus eye
0 MAAFALPEGFTEFDMFTFGSALLVG 1
2 GLIGFFLNAISIASFLRVKEMWNPSNFFVFNLAVADICLNVNGLTAAYASYLR 2
1 YWPFGQDGCTFHAFQGMIAVLASISFMGVIAWDRYHQYCT 1
2 RQKLFWSTTLTMSAIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTKGDR 2
1 DYVTYMLTLVFLYLMFPALTMWSCYDAIHKHFKKIHLHK 0
0 FNTSTPLRVLLMCWGPYVLMCIYACFENVKVVSPKLRM 0
0 LLPVVAkTNPIFNALLYSFGNEFYRGGVWHFLTGQKMVDPVVKKSK* 0

>RGR2_oryLat Oryzias latipes (medaka) whole embryo 68% identical RGR2_danRer
0 MGTHTLPEGFTDFDMFTFGSALLVG 1
2 GLLGFFLNAISILAFLRVKEMRSPSSFLVFNLALADISLNINGLTAAYASYLR 2
1 YWPFGQEGCDYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTSITISLIIWILSILWSAFPLMGWGVYDFEPMRIGCTLDYTKGDR 2
1 DYITYMLSLVFFYLMFPAFIMLSCYDAIYKHFKKIHYYR 0
0 FNTSLPLRVMLMCWGPYVLMCIYACFENVKLVSPKLRM 0
0 LPVIAKTNPFFNALLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSKQK* 0

>RGR2_gadMor Gadus morhua larvae 
0 MAAYALPEGFEEFDMFTFGTALLVG 1
2 GMIGFILNAITIVAYLRVKEMRTPSNFFVFNLALADLSLNINGLTAAYASYAR 2
1 QWPFGQSGCSYHGFQGMISVLASISFMAAISWDRYHQYCT 1
2 RQKLFWSTTVTMCCIVWVLSVFWAALPLIGWGVYDFEPMRVGCTLDYTIGDR 2
1 DYITYMLSLVVFYLLFPAYTMMSSYDAINKHFRKIHLQK 0
0 FNTKLPLSVMLACWGPYVLMCVYACFENVKIVSPKLRM 0
0 VLPVLAKTNPISNALLYSFGNESYRSGVWHFLTGQKFVEPSFKKIK*

>RGR2_oncMyk Oncorhynchus mykiss (trout)
0 MAAYTLPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNAISILAYISVKQMRTPSNFLVFNLAVADIVLNLNGLIAAYASLFYR 2
1 HWPWGQDGCSNHAFMGMTAVLASISFLAAIAWDRYHQYVT 1
2 NQKLFWSTAWTISIIIWGLAIIWAAVPLIGWGVYDFEPMRTCCTLDYTKGDN 2
1 DYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHR 0
0 WNTSIPLRVLLFCWGPYEIMCIYACFGNARLSPKLRM 0
0 LLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR*

>RGR2_esoLuc Esox lucius (pike) fragment
0 MAAYTLPEGFSDFDMVAFGSALLVG 1
2 GLAGFFLNATSILAFVSVKQMRTPSNFLVFNLAVADIMLNTSGLIAAYASLSYR 2
1 HWPWGQDGCSNHAFFGMTAVLTSISFLAVIAWDRYHQYVT 1
2 NQKLFWSTAWTFSIIIWGMAIFWAYVPLTGWGVYDFEPMRTCCTLDY 

>RGR2_hipHip Hippoglossus hippoglossus (halibut) fragment
0 MAAFTLPEGFTDFDMFTFGTALLVG 1
2 GMLGFVLNAISIVSFLTVKEMRNPSNFFVFNLAVADLCLNINGLTAAYASYLR 2
1 YWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSGIIWILSIFWAAVPLMGWGAYYFEPMKTCCTLDYTRGDR 2
1 DYVTYMLTLV

>RGR2_poeRet Poecilia reticulata fragment
2   GLTAAYASYLR 2
1 YWPFGQEGCNYHAFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSGIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTRGDR 2
1 DYITYMLTLTVLYLTFPAVTMSSCYDSIYKHFKKIHHHR 0
0 FNTSLPLRVLLSCWGPYVLMCTYACFENVKLVSPKLRM 0
0 LLPVVAKTNPIFNAFLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSK* 0

Regularized RGR sequences

Here both RGR1 and RGR2 sequences are optimized for purpose of alignment by filling in missing exons, correcting for probable sequence error, and removing one-off anomalies confined to single species. In this process, the nearest neighbor in the phylogenetic tree is used for missing or erroneous data (eg rabbit for pika). This removes various irrelevencies that distract from Multalign or ClustalW output.

>RGR_homSap Homo sapiens (human) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKREKDRTK* 0

>RGR_panTro Pan troglodytes (chimp) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAIPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK* 0

>RGR_gorGor Gorilla gorilla (gorilla) 0 1
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLAPAESGISLNALVGATSTLLG 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSTLACKSAVSLVLSGRMSSAFWADLPLLGWGPYDYEPLRTCCTLDYSEADR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSKKDRTK* 0

>RGR_ponPyg Pongo pygmaeus (orang_abelii) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAVLYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK * 0

>RGR_nomLeu Nomascus leucogenys (gibbon) 
0 MAETSVLPTGFGELKLLAGGMGLLAE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAVNYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_macMul Macaca mulatta (rhesus) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_papHam Papio hamadryas (baboon) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_calJac Callithrix jacchus (marmoset) 
0 MAESSTLPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSTFWAAFPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTIDAINYALGNEMICRGIWQCLSPQKSEKDRTK* 0

>RGR_tarSyr Tarsius syrichta (tarsier) 
0 MAEAGALPAGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLR 2
1 RWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCT 1
2 GSQLAWNTAISLVLFVWLSYAFWAALPLLGWGHYDYEPLGTCCTLEYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQ 0
0 VNTTLPIRTLMLGWGPYALLYLCAVIADVTSISPKLQM 0
0 VPALIAKTVPTINAYHYALGSEMVCRGIWQCLSPHSSEQDRAK* 0

>RGR_otoGar Otolemur garnettii (bushbaby) 
0 MAEPGTLPAGFGEIEVLAVGTVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLR 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GRPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYDYEPLRTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLTPLFITLTSYQLMEQKLRRSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATIADVTSISPKLQM 0
0 VPALIAKTVPTINAVNYALGSEMVCRGIWQCLSLQRSKQDGAK* 0

>RGR_micMur Microcebus murinus (mouse_lemur) 
0 MAEPGTLPTGFRELEVLAVGTVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLR 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NVTSFLFTMAFFNFLIPLFITHTSYQLMEQKLKKSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATVADVTSISPKLQM 0
0 VPALIAKTVPTINAINYALGSETVCRGIWQCLSPQRSEQDRAK* 0

>RGR_tupBel Tupaia belangeri (treeshrew) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTVFSFCKSPELRTPSHLLVLSVALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCT 1
2 GSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLMPLFITLTSYWLMEEKLRKGGRLQ 0
0 VNTTLPSRTLLLGWGPYALLYLYAAFADVTPLSPKLQM 0
0 VPALVAKMVPTVNAVNYALGSETICRGIWGCLSPqKRERDRAR* 0

>RGR_musMus Mus musculus (mouse) 
0 MAATRALPAGLGELEVLAVGTVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLP 0
0 VNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALHREMVCRGTWQCLSPQKSKKDRTQ* 0

>RGR_ratNor Rattus norvegicus (rat) 
0 MTATRALPAGFGELEVLAIGIVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWLSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKLSRSGHLQ 0
0 VNTTLPGRMLLLGWGPYALLYLYAAVADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALRSEMVCRGTWQCRSAQKSKQDRTQ* 0

>RGR_speTri Spermophilus tridecemlineatus (ground_squirrel) 
0 MAETAALPAGFGELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELRTPNHLLLLSLAVADSGISLNALIAAISSLLR 2
1 RWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAIPLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFFVPLFITLTSYRLMEQKLARSGHLQ 0
0 VNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQM 0
0 VPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ * 0

>RGR_dipOrd Dipodomys ordii (kangaroo_rat) 
0 MATSGDLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPIHLLDLSLAVADSGISLNALIAAISSLEW 2
1 HWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCT 1
2 GSLLGWDTAVSLVIFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLVPLFITLTSYQLMKQKFARSGRLQ 0
0 VNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQM 0
0 VPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ* 0

>RGR_cavPor Cavia porcellus (guinea_pig) 
0 MATSEALPAGFGELEVLAVGTVLLLE 1
2 GLCGLSLNGLTVVSFWKSPALRTPNHLLVLSLALADSGLSLNALVAAGSSLLR 2
1 HWPyGSGHCQALGFQGFTTALASISGTAALSWGRCHHHCT 1
2 RGRLTWSTAVPLVLFVWLSSAFWAALPLLGWGRYDYEPLGTCCTLDYSTGDR 2
1 NFTSFLFTMAFFNFLVPLFITVTSCQLMERHLARSSRLQ 0
0 VSVRQPARTLLLCWgPYALLYLYAVLADAHTLSPRLQM 0
0 VPALIAKTVPTINAINYALCNELLCGGFSLGLLPQKGKQDRTQ* 0

>RGR_oryCun Oryctolagus cuniculus (rabbit) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELWTPSHLLVLSLAVADSGISLNALIAAVSSLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLITMAFFNFLMPLFITLTSYSLMEQKLSKSGRLQ 0
0 VNTTLPGRTLLFCWGPYAVLYLCAAVADMSSITLKLQM 0
0 VPALIAKTVPTVNAVNYALGSEVIRRGIWQCLLPQRSVRGRAQ* 0

>RGR_ochPri Ochotona princeps (pika) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTMAFFNFLMPLFIMLTSYSLMEQKLAKSGRLQ 0
0 VNTTLPARTLLFCWGPYAILCLCATVMDMSTVSPKLLM 0
0 VPALIAKAVPTVNAINYALGSEVIRRGIWQCLLPQRSVRDRAQ* 0

>RGR_canFam Canis familiaris (dog) 
0 MADSGALPAGFGELEVLAVGTVLLVE 1
2 ALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLR 2
1 RWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCT 1
2 RGQLAWNTAISLVLCVWLSSVFWAALPLLGWGRYDYEPLGTCCTLDYSRVDR 2
1 NFTSYLFTMAFFNFFLPLLITLVSYRLMEQKLKKPGHLQ 0
0 VSTTVPARTLLLCWGPYALLYLYATVADVRSVPPKLQM 0
0 VPALIAKAAPTINAIHYALGGDMVHGGLWQCLSPQRSQPDRAR* 0

>RGR_felCat Felis catus (cat) 
0 MAESGSLPTGFGELEVLAVGMVLLVE 1
2 ALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLR 2
1 RWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCS 1
2 GSQLAWNTAISLVICVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFFMPLFITFISYRLMEQKLRKTGHLQ 0
0 VNTTLPARTLLFGWGPYALLYLYATIADVSSVSPKLQM 0
0 VPALIAKAAPTINAINYALGSEMVHRGIWQCLSPQGSGLDRAR* 0

>RGR_bosTau Bos taurus (cow) 
0 MAESGTLPTGFGELEVLAVGTVLLVE 1
2 ALSGLSLNILTILSFCKTPELRTPSHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLLPLFITVVSYRLMEQKLGKTSRPP 0
0 VNTVLPARTLLLGWGPYALLYLYATIADATSISPKLQM 0
0 VPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ* 0

>RGR_turTru Tursiops truncatus (dolphin) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTILCFCKNPELRTPSHLLVLSLALSDSGISLNALMAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWATLPLLGWGHYDREPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFLLPLFITVISYRLMEQKLGKTGRPP 0
0 VNTVLPARTLLFGWGPYALLYLYAAVADVTSISPKLQM 0
0 VPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ * 0

>RGR_susScr Sus scrofa (pig) 
0 MAEPGALPTGFGELEVLAVGTLLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPSHLLVLSLALADSGISLNAFVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 RSRLDWNTAVSLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRVDR 2
1 NFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPP 0
0 VNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQM 0
0 VPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ* 0

>RGR_vicVic Vicugna vicugna (vicugna) 
0 MAESRALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPNHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GSRLDWNTAVSLVFFVWLSSTCWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPP 0
0 VNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQM 0
0 VPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ * 0

>RGR_equCab Equus caballus (horse) 
0 MAESGSLPTGFRELEVLAVGTVLLVE 1
2 ALAGLSLNSLTILSFCKTPELRTPSHLLVLSLAVADSGLSLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSRLAWNTAVFLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLLTMAFFNLLLPLLITLTSYRLMEQKLGKTGQLQ 0
0 VNTTLPARTLLLCWGPYALLYLYATVADATSISPKLRM 0
0 VPALVAKTVPTINAVNYALGSEMLHRGIWQCLSPQKSERDRAQ* 0

>RGR_myoLuc Myotis lucifugus (microbat) 
0 MAEAGSLPTGFGELEVLAVGVVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCT 1
2 GSRLAWRTAASLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCSLGYARGSR 2
1 NFTSFLFLMAFFNFLLPLFITFTSYRLMEQKLGRTRPPQ 0
0 VNTTLPARTLLLGWGPYALLHLCAALAGTALIPPRLQV 0
0 VPALIAKMVPTVNAVNYALGSEMVQRGIWQCLSPQRSERDHAQ* 0

>RGR_pteVam Pteropus vampyrus (macrobat) 
0 MAESRSLPTVFWELEVLAVGTVLMVE 1
2 ALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GSRLAWNTAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFVLPLFITLTSYQLMEQKLGKTGHPQ 0
0 VNTTLPARTLMLCWGPYALLYLYAAVMDVASISPKLQM 0
0 VPALIAKMAPTINAVNYALGSEMVQRGIWQCLSPQRSERDHAQ* 0

>RGR_sorAra Sorex araneus (shrew) 
0 MTESGALPAGFKELKMLAVGTLLLWG 1
2 ALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GRQLAWDVAIALVIFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGGR 2
1 NFVSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKMGQPQ 0
0 VNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQM 0
0 VPALIAKTVPTVNALHYGLGSGMVQNGFRKGLWLQRRERERAL* 0

>RGR_eriEur Erinaceus europaeus (hedgehog) 
0 MTESGALPAGFKELKMLAVGTLLLWG 1
2 ALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCT 1
2 RSRLAWNTAVFLVFFVWVSSVFWAALPLLGWGHYDYEPLGTCCTLDYSSGDR 2
1 NFISFLFTMAFFNFLLPLFITLISYQLMEQKLRKTGHPQ 0
0 VNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQM 0
0 VPALIAMVPTVNAVHYVLGSEKVHKGFWQCFSPQRSEQDRAR* 0

>RGR_loxAfr Loxodonta africana (elephant) 
0 MAEPGHLPAGFQELEVLTVGTVLLLE 1
2 ALSGLSLNGLTILSFCKIPELRTPGHLLVLSLALADSGISLNALVAAMSSLRR 2
1 RWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCT 1
2 RSRLAWSSASALVLFVWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLLTMAFFNFLLPLFITLTSYRLMEQKLKKKGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLCAAATDMTSISPRLQM 0
0 VPALVAKAVPVINACHYALGSEVVRGGIWQYLSRQRGESPLRARDRTH* 0

>RGR_proCap Procavia capensis (hyrax) 
0 MADPRPLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRG 2
1 RWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCT 1
2 GSKLAWSSAGALVLFMWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLFTMAFFNFLLPLFITLASYRLMEQKLKKEGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLYTAITDVNSISPKLQM 0
0 VPALIAKAVPIVNACHYALGSETVHRGIWQCLSRQRGESPPRTRDRTQ* 0

>RGR_echTel Echinops telfairi (tenrec) 
0 MVEPRTLPPGFGELEVLAVGTVLLVE 1
2 ALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRG 2
1 HWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCT 1
2 GSQFTWSSASTLVLFMWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMTFFNFSMPILVTLTSYQLMQQKLKKSGPLQ 0
0 VNTTLPTRTLLLGWGPYALLYLCAACTDVTGISPKLQM 0
0 VPAIVAKAVPIVNACHYALGNKVLRRGIWQFLSQQSGRPLSSQDRTQ* 0

>RGR_dasNov Dasypus novemcinctus (armadillo) 
0 MAGSGVLPPGFGELEVLAVGTVLLVE 1
2 ALSGLVLNGLAIISFCKTPELRSPSRLLVLSLALADSGVSLNALVAATSSLLR 2
1 RWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCI 1
2 GRRLAWSTAGCLVLCLWMAAAFWAALPLLGWGLYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQ 0
0 VSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQM 0
0 VPALIAKTMPTVNALYYALGRESVHRNA* 0

>RGR_choHof Choloepus hoffmanni (sloth) 
0 MAESRVLPTGFGELEVLAVGIVLLVE 1
2 ALSGLTLNGLTLFSFCKTPELQRPSHLLVLSLALADSGVSLNALLAATASLIG 2
1 RWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCT 1
2 GSQLSWSTAGSLVLCVWLSSVFWATLPILGWGHYDYEPLGTCCTLGYSRGDR 2
1 NFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQ 0
0 VSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQM 0
0 VPALIAKTMPTINAFQYALGSETVCRDIWQCLPRLRSMGRSSGHD* 0

>RGR_ornAna Ornithorhynchus anatinus (platypus) 
0 MVTSHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGLCLNGLTIASFRKIKELRTPSNLLVVSLALADSGICLNALMAALSSFLR 2
1 HWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCS 1
2 RSKPQWGTAVSTVLFAWGFSAFWSMMPILGWGQYDYEPLRTCCTLDYSKGDR 2
1 NFTTYLFAVAFFNFVIPLFIMLTSYQSIEQRFKKSGLFK 0
0 LNTRLPTRTLLFCWGPYALLCFYATVENVTFISPKLRM 0
0 IPALIAKTVPVIDAFTYALRNEDYRGGIWQFLTGQKIERVEVENKIK* 0

>RGR_anoCar Anolis carolinensis (lizard) 
0 MVTAYPVPEGFTDLEVFVIGTALLVE 1
2 ALLGFSLNMLTIVSFWKIKELRTPGNFLVFNLALSDCGICFNAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCT 1
2 GNKLQWGSVIPMTIFLWLFSGFWAAMPLLGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYITYLIPLALFHFMIPGFIMLTAYQAIDHKFKKTGQFK 0
0 FNTGLPVKSLVICWGPYSFLCFYAAVESVTFISPKILM 0
0 IPAVIAKSSPAANALIYALGNENYQGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_galGal Gallus gallus (chicken) 
0 MVTSHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCT 1
2 RSKLQWSTAISMMVFAWLFAAFWATMPLLGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYITFLFALSIFNFMIPGFIMMTAYQSIHQKFKKSGHYK 0
0 FNTGLPLKTLVICWGPYCLLSFYAAIENVMFISPKYRM 0
0 IPAIIAKTVPTVDSFVYALGNENYRGGIWQFLTGQKIEKAEVDSKTK* 0

>RGR_taeGut Taeniopygia guttata (finch) 
0 MVTAHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCT 1
2 RSRLQWSTAVSMMVFAWLFAAFWSVMPLLGWGKYDYEPLRTCCTLDYSKGDR 2
1 NYVTFLFALSTFNFMIPGFIMMTAYQSIHQKFRKTGHFK 0
0 FNTGLPLKTLVICWGPYCLLCTYAAVENVMFIPPKYRM 0
0 IPALIAKTVPTVDAFIYALGNENYRGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_xenTro Xenopus tropicalis (frog) 
0 MVTSYPLPEGFTETEVFAIGTTLLVE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWSTAVSVVFFIWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYISYLFTMAFFEFLVPLFILMTAYQSIYQKMKKSGQIR 0
0 FNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 IPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKLEKAETDNKTK* 0

>RGR_xenLae Xenopus laevis (frog) NM_001092855 mRNA
0 MVTSYPLPEGFTETEVFAIGTTLLIE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWGTAVSMVLFVWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NFTSFLFTMAFFEFLVPVFILLTAYQSIYQKMKKSGQIR 0
0 LNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 MPALLAKISPAVNAYVYGLGNENYRGGIWLYLTGQKLEKAETDSRTK* 0

>RGR1_danRer Danio rerio (zebrafish) 
0 MVTSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVLFTWLFTAFWAAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAK 0
0 FNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 IAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKIESPAIENKSK* 0

>RGR1_takRub Takifugu rubripes (fugu) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPSTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTINVFLYALGNENYRGGIWQFLTGEKIEAPQIENKSK* 0

>RGR1_tetNig Tetraodon nigroviridis (pufferfish) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFFKVRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLVPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPNTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTVNVFLYALGNENYRGGIWQFLTGEKIETPQLENKTK* 0

>RGR1_gasAcu Gasterosteus aculeatus (stickleback) 
0 MVSSYPLPDGFTDFDVFSLGSCLLVE 1
2 GLLGILLNAVTIAAFLKVRELRTPSNFLVFSLAVADIGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFVWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYVSYLIPMAIFNMAIQVFVVMSSYQSIAQKFKKTGNPR 0
0 FNPNTPLKAMLFCWGPYGILAFYAAVENATLVSTKLRM 0
0 MAPILAKTSPTFNVFLYALGNENYRGGIWQLLTGEKIDVPQIENKSK* 0

>RGR1_oryLat Oryzias latipes (medaka) 
0 MATSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGIFLNSVTIVAFLKVRELRTPSNFLVFSLAMADIGISMNATIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSTAITLAVLVWIFTAFWAAMPLIGWGEYDYEPLRTCCTLDISKGDR 2
1 NYVSYVIPMSIFNMGIQVFVVMSSYQSIAQKFQKTGNPR 0
0 FNASTPLKTLLFCWGPYGILAFYAAVADANLVSPKIRM 0
0 IAPILAKTSPTFNPLLYALGNENYRGGIWQFLTGEKIHVPQDDNKSK* 0

>RGR1_gadMor Gadus morhua (cod) ES469757
0 MVSAYPLPEGFSDFDVFSFGSFLLVE 1
2 GLLGIILNAVTIVAFCKVKELRTPSNFLVFSLAMADIGISMNASVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCT 1
2 RTELQWSSAVTLSVFIWLFSAFWSAMPLIGWGTYDYEPLRSCCTLDYTKGDR 2
1 NYVSYLIPMTVFNMVVQIFVVMSSYQSIDQKFKKTAKPK 0
0 FNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRM 0
0 MAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK* 0

>RGR1_pimPro Pimephales promela DT198813 frag
0 MVTYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKIRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVIFIWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIERKFQKSGQAK 0
0 FNCSTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 MAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK* 0

>RGR1_osmMor Osmerus mordax (smelt) EL524757 frag
0 MVSSYPLPDGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISSNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVMFIWLFTAFWSAIPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMAIQIFVVLSSYQSIDQKFKKTAKPK 0
0 FNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRM 0
0 MAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK* 0

>RGR_calMil Callorhinchus milii (elephantfish) frag
0 MVSSYPLPEGFTDFEVFGLGTALLVE 1
2 GLVGLLLNGLTLLAFYKIKELRTPSNLLITSLALSDFGISMNAFIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCS 1
2 RSRLQWSSAITVTVFIWGIAAFWSAMPLLGWGVYDYEPLRTCCTLDYSKGDR 2
1 NFISFFIIMGSFEFIFPIFIMLSSYQSCKSKFKKNGQVK 0
0 FNTGLPVKTLIFCWGPYSLLCFYATIENITILSPKLRM 0
0 IPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKLEKAETDNKTK* 0


>RGR2_danRer zebrafish NM_001024436 embryonic RPE, brain, gut, embryo PA indel
0 MASYPLPEGFTDFDMFAFGSALLVG 1
2 GLLGFFLNAISVLAFLRVREMQTPNNFFIFNLAVADLSLNINGLVAAYACYLR 2
1 HWPFGSEGCQLHAFQGMVSILAAISFLGAVAWDRYHQYCT 1
2 KQKMFWSTSITISCLIWILAVFWAAMPLIGWGVFDFEPLRTCCTLDYSQGDR 2 
1 GYITYMLTITVLYLAFPVLVLQSSYSAIHAYFKKTHHYR 0
0 FNTGLPLKALLFCWGPYVVVCSLACFEDVSVLSPRLRM 0
0 VLPVLAKTSPIFHAVLYAYGNEFYRGGVWQFLTGQKSADKKK* 0

>RGR2_pimPro Pimephales promelas liver brain PA indel
0 MASYALPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNLISVLAFLRVREIQTPNNFFIFNLAVADLSLNINGLVAAYASYLR 2
1 YWPFGSEGCQIHGFQGMVSILASISFLGAIAWDRYHLYCT 1
2 KQKMFWSTSGTISALIWILAVFWAALPLIGWGVFDFEPMRTCCTLDYTIGDR 2
1 NYISYMLTITVLYLAFPVLIMQSSYNGIYAHFKKTHHFK 0
0 FNTGLPLKMLLFCWGPYVLMCTYACFENASLVSPKLRM 0
0 VLPVLAKTSPIFHAAMYAYGNEFYRGGIWQFLTGQKPADKKK* 0

>RGR2_tetNig Tetraodon nigroviridis eyes
0 MAAYTLPEGFTEFDMFTFGTALLVG 1
2 GVLGFFLNAISIVSFLTVKEMRNPSNFFVFNLALADISLNVNGLIAAYASYLR 2
1 YWPFGQDGCSYHAFHGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSSIIWILSIFWSAVPLMGWGVYDFEPMRTCCTLDYTRGDR 2
1 DYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHR 0
0 FNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRM 0
0 LLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK* 0

>RGR2_gasAcu Gasterosteus aculeatus eye
0 MAAFALPEGFTEFDMFTFGSALLVG 1
2 GLIGFFLNAISIASFLRVKEMWNPSNFFVFNLAVADICLNVNGLTAAYASYLR 2
1 YWPFGQDGCTFHAFQGMIAVLASISFMGVIAWDRYHQYCT 1
2 RQKLFWSTTLTMSAIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTKGDR 2
1 DYVTYMLTLVFLYLMFPALTMWSCYDAIHKHFKKIHLHK 0
0 FNTSTPLRVLLMCWGPYVLMCIYACFENVKVVSPKLRM 0
0 LLPVVAkTNPIFNALLYSFGNEFYRGGVWHFLTGQKMVDPVVKKSK* 0

>RGR2_oryLat Oryzias latipes (medaka) whole embryo 68% identical RGR2_danRer
0 MGTHTLPEGFTDFDMFTFGSALLVG 1
2 GLLGFFLNAISILAFLRVKEMRSPSSFLVFNLALADISLNINGLTAAYASYLR 2
1 YWPFGQEGCDYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTSITISLIIWILSILWSAFPLMGWGVYDFEPMRIGCTLDYTKGDR 2
1 DYITYMLSLVFFYLMFPAFIMLSCYDAIYKHFKKIHYYR 0
0 FNTSLPLRVMLMCWGPYVLMCIYACFENVKLVSPKLRM 0
0 LPVIAKTNPFFNALLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSKQK* 0

>RGR2_gadMor Gadus morhua larvae 
0 MAAYALPEGFEEFDMFTFGTALLVG 1
2 GMIGFILNAITIVAYLRVKEMRTPSNFFVFNLALADLSLNINGLTAAYASYAR 2
1 QWPFGQSGCSYHGFQGMISVLASISFMAAISWDRYHQYCT 1
2 RQKLFWSTTVTMCCIVWVLSVFWAALPLIGWGVYDFEPMRVGCTLDYTIGDR 2
1 DYITYMLSLVVFYLLFPAYTMMSSYDAINKHFRKIHLQK 0
0 FNTKLPLSVMLACWGPYVLMCVYACFENVKIVSPKLRM 0
0 VLPVLAKTNPISNALLYSFGNESYRSGVWHFLTGQKFVEPSFKKIK*

>RGR2_oncMyk Oncorhynchus mykiss (trout)
0 MAAYTLPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNAISILAYISVKQMRTPSNFLVFNLAVADIVLNLNGLIAAYASFYR 2
1 HWPWGQDGCSNHAFMGMTAVLASISFLAAIAWDRYHQYVT 1
2 NQKLFWSTAWTISIIIWGLAIIWAAVPLIGWGVYDFEPMRTCCTLDYTKGDN 2
1 DYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHR 0
0 WNTSIPLRVLLFCWGPYEIMCIYACFENVKIVSPKLRM 0
0 LLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR*

>RGR2_esoLuc Esox lucius (pike) fragment
0 MAAYTLPEGFSDFDMVAFGSALLVG 1
2 GLAGFFLNATSILAFVSVKQMRTPSNFLVFNLAVADIMLNTSGLIAAYASSYR 2
1 HWPWGQDGCSNHAFFGMTAVLTSISFLAVIAWDRYHQYVT 1
2 NQKLFWSTAWTFSIIIWGMAIFWAYVPLTGWGVYDFEPMRTCCTLDYTKGDN 2
1 DYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHR 0
0 WNTSIPLRVLLFCWGPYEIMCIYACFENVKIVSPKLRM 0
0 LLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR* 

>RGR2_hipHip Hippoglossus hippoglossus (halibut) fragment
0 MAAFTLPEGFTDFDMFTFGTALLVG 1
2 GMLGFVLNAISIVSFLTVKEMRNPSNFFVFNLAVADLCLNINGLTAAYASYLR 2
1 YWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSGIIWILSIFWAAVPLMGWGAYYFEPMKTCCTLDYTRGDR 2
1 DYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHR 0
0 FNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRM 0
0 LLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK* 0

@@ Line 106: / Line 106: @@
 [[Image:Opsin_RGR_active.png|left]]
-Notably absent are RGR genes in marsupials; for other genes, marsupial representatives are typically available from 2-3 species. By locating syntenic genes in placental mammals and platypus, the appropriate region of the opossum genome can be identified. However the adjacent orthologs are now on separate autosomal opossum chromosomes, suggesting a translocation has disrupted the RGR genes. None of the individual exons can be found by tblastn of the genome or blastn of the very extensive trace archive coverage. This lack of even pseudogene debris supports the idea of gene loss and decay sometime after marsupial divergence.
+Notably absent are RGR genes in marsupials; for other genes, marsupial representatives are typically available from 2-3 species. By locating syntenic genes in placental mammals and platypus, the appropriate region of the opossum genome can be identified. However the adjacent orthologs are now on separate autosomal opossum chromosomes, suggesting a translocation has disrupted the RGR genes. None of the individual exons can be found by tblastn of the genome or blastn of the very extensive trace archive coverage. This lack of even pseudogene debris supports the idea of gene loss and decay sometime fairly soon after marsupial divergence.
-The loss of RGR in marsupials further challenges the usual functional explanation given to RGR in placental mammals (a complex with 11-cis-retinol dehydrogenase RDH5 that replenishes cis-retinal at cone and rod opsins). Since marsupials are known from experiment to have normal color and rod vision, either other pathways for replenishment exist or the role of RGR was somewhat different in the ancestor.
+The loss of RGR in marsupials further challenges the usual functional explanation given to RGR in placental mammals (a complex with 11-cis-retinol dehydrogenase RDH5 that replenishes cis-retinal at cone and rod opsins). Since marsupials are known from experiment to have normal color and rod vision via ciliary opsins, either other pathways for replenishment exist or the role of RGR was different in the theran ancestor.
 If RGR has 1/5th the quantum efficiency of  rod rhodopsin and 1/100th its abundance, the question arises how it keeps up with bright light replenishment needs. Furthermore, [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12716426 knockout mice] develop a normal retina and RP epithelium without any morphological phenotype (unlike those lacking trans-retinol isomerase RPE65), whereas humans even heterozygous in RGR for Ser66Arg exhibit ERG abnormalities and eventually retinitis pigmentosa and RPE degeneration.
-Most experimental work has unfortunately been done on GRY species whereas platypus and earlier diverging species have the more conventional DRY or ERY. Thus the role of RGR could have drastically shifted at the time of marsupial divergence. They lost the gene altogether while placentals retained it but likely with a rather altered signaling properties and functionalities.
+Most experimental work has unfortunately been done on GRY species whereas platypus and earlier diverging species have the more conventional DRY or ERY, as do afrotheres and xenarthrans (implying this for the lost marsupial and stem RGR). Thus the role of RGR could have drastically shifted after elephant/sloth divergence. Marsupials lost the gene altogether while placentals retained it but by the time of boreoeutheran divergence with a rather altered signaling properties and functionalities.
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Opsin evolution: RGR phyloSNPs: Difference between revisions

Latest revision as of 21:33, 22 November 2010

Contents

Introduction to RGR Opsin Evolution

A Curated Set of 54 RGR Opsins

Comparative genomics of RGR at E/DRY

PhyloSNPs in RGR

Loss of RGR in marsupials

Gain of RGR2 paralog in teleost fish

Alignment of all RGR sequences

RGR signaling in olfactory bulb and retinal pigmented epithelium

Local splice migration and exon-skipping in RGR opsins

RGR curated reference sequences

RGR reference sequences from 51 vertebrates

RGR2 reference sequences from 9 teleost fish

Regularized RGR sequences

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