Opsin evolution: RPE65

Introduction to the RPE65 gene family

This gene family is critical to the metabolism of provitamin A dietary carotenoids and thus to retinoic acid signaling and the recycling of all-trans retinal needed to replenish vertebrate ciliary opsins after exposure to light. RPE65, as its illegimate but irrevocably established gene name suggests, is a protein of 61 kdaltons found in the retinal pigment epithelium adjacent to photoreceptor layers. It isomerizes all-trans-retinyl palmitate extracted from phospholipid membranes to 11-cis-retinol.

In vertebrates including human, RPE65 has two full-length paralogs on different chromosomes, BCMO1 (ß-carotene-15,15'-oxygenase cleaving symmetricaly to yield two retinals) and BCO2 (ß-carotene-9',10'-oxygenase cleaving asymmetricaly to yield a retinoic acid precursor and also cleaving lycopene), as recently reviewed. Insects have but a single gene NinaB but as shown below, this is attributable to gene loss rather than being the ancestral bilateran state.

The nomenclature of these three genes violates the spirit and letter of international agreement for naming human gene families, yet the responsible committee has approved the names! While an improvement over monstrosities such as B-DIOX-II and BCDO2 beta-carotene dioxygenase (for a mono-oxygenase!), it should be noted that RPE65 is 61 kd and expressed in a great many other tissues (such as skin) beyond retinal pigment epithelium (where BCMO1 also occurs). A more appropriate nomenclature capturing the paralogous relationships and key features might be BCO1S, BCO2A, and BCO3R, where the letters denote symmetric, asymmetric, and retinal.

This gene family is readily tracked back to bacteria where a 3D structure has been determined that suffices to model the entire family in all species. Four invariant histidines that hold the catalytic ferrous iron lie on the axis of a seven-bladed beta-propeller fold. The Fe2+ is accessible to carotenoids via a long nonpolar tunnel capable of promoting cis-trans double bond conversions. RPE65 shares all these features even though as a mere isomerase.

Since this complex structure consists of a single coherent domain fold, alternative coding splices can be dismissed out of hand as transcriptional noise not leading to stable functional enzyme. The domain structure implies all homologs from all species must be full length or around 550 amino acids, which is validated below over tens of billions of years of evolutionary branch length. That conclusion must be qualified to the extent that N- and C-terminal extensions could be trimmed post-translationally and small indels not affecting the propellers might be tolerated.

RPE65 is a well-known disease gene for retinitis pigmentosa and type II Leber congenital amaurosis. Its two paralogs are not currently associated with human disease but have various consequences in knockout mice consistent with enzymatic expectations. Retinol dehydrogenase RDH5 is associated with fundus albipunctatus; LRAT lecithin retinol acyltransferase with severe, early-onset retinal dystrophy.

Mouse knockouts have been studied for RPE65, BCMO1, LRAT, and curiously RGR opsin which mediates all-trans retinyl ester mobilization from lipid droplet storage to the endoplasmic reticulum explaining the intrinsic light sensitivity of the retinal pigment epithelium.

Vitamin A (all-trans-retinol) is a commercial dietary substitute for natural dietary carotenoids that itself is a waste product of the ciliary opsin photoreception but scavengible to 11-cis-retinal (and related opsin chromophores such as 11-cis-3-hydroxy-retinal) and retinoic acid (all-trans and 9-cis). Less characterized asymmetric BCO2 cleavage products may have unsuspected functionality. Retinoic acid is a ligand regulating gene transcription via heterodimeric nuclear hormone receptors (RA receptor and retinoid X receptor RXR) as recently reviewed. CMO1 is transcriptionally regulated by various heterodimers of RXR including PPARs (peroxisome proliferator-activated receptors).

The confused history of RPE65

RPE65 has a history of serious experimental and interpretive error assigning its isomerase activity to LRAT (ecithin:retinol acyl transferase), assigning palmitolyation to various RPE65 cysteine residues that did not occur, and attributing its (non-transiting) membrane association to these lipids when in fact that is intrinsic to a surface hydrophobic patch. Still earlier confusion over enzyme mechanism introduced dioxygenases for BCO2 (which is a mono-oxygenase like BCMO1).

While this June 2004 paper conflicted from the get-go with full-length alignment of RPE65 to well-studied carotenoid isomeroxygenases, the brief debacle exposed a multi-year delay in update cycling at primary hub databases such as RefSeq, SwissProt, and OMIM. None of these have not been corrected 55 months later. It's not clear when these pivotal descriptions will ever be revisited. Meanwhile hundreds of derived databases continue to perpetuate serious misunderstandings about this important but straighforward disease gene and the visual pigment cycle in vertebrates. How many thousands of other genes lie outside an update cycle?

The current view of retinal cycling in vertebrate eyes envisions the primary photosensitive event as isomerization of opsin-bound 11-cis retinal to all-trans retinol. After importation to the adjacent retinal pigment epithelia, that is esterified by LRAT palmitolyation and subsequently isomerized by RPE65 to 11-cis retinol, which must then be oxidized to 11-cis retinal by RDH5 before it can be re-exported back to the retina and re-form its Schiff base in a newly recharged opsin molecule. This system seems quite bizarre in comparison to self-recharging insect melanopsins.

BCO2 role in chicken yellow skin

It turns out that Darwin was wrong about domestic chicken: it is a hybrid of two south Asian species of junglefowl, red junglefowl (Gallus gallus) and closely related grey junglefowl (Gallus sonneratii). This was proposed in 1949 by Hirt but only recently confirmed by extensive mapping of the recessive allele for yellow skin and yellow legs.

Most likely, this can be attributed to a cis-regulatory region just upstream of BCO2 that apparently reduces gene expression in skin, resulting in dietary carotenoids accumulating there. While the exact causal mutation cannot yet be identified within the minimum 23.8 kb haplotype chr24:6,264,083-6,287,900 May 06 assembly coordinates, it is very unlikely to be the only non-synonymous SNP in this region because as shown below it occurs at a highly variable position in poorly conserved exon 8 of a rapidly evolving overall gene (67% identity between chicken and human orthologs).

Thus BCDO2 regulation (rather than coding sequence per se) could be selectively important (for mating displays) by controlling skin, scale, and feather carotenoid pigmentation in birds, fish and other vertebrates. If so, it would be an important example of evolution at the regulatory level rather than at protein sequence.

In terms of domestication, early farmers may have wanted egg yolks with extensive carotenoids coloring and may have taken bright yellow skin as a proxy for healthy birds, thus imposing selection on their flocks, though QTL studies today do not support such an association.

Two chicken ESTs (CN221314 and DR424873) indicate that the promoter region and its CpG island occur upstream of 6282641, suggesting that the SNP should be located in the 5,260 bp region between there and 6287900. However no striking conserved non-coding region exists in chicken; human regulatory tracks at the UCSC also do not illuminate how or where expression is regulated here.

The K416N SNP can be N, G, D, E, H, L, K, and R in vertebrate orthologs indicating no catalytic significance:
                              *
>BCO2_homSap VHNSAAKSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGT
>BCO2_panTro VHNSAAKSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGT
>BCO2_ponPyg VYNSAAKSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGT
>BCO2_macMul VYNSAGRSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGT
>BCO2_calJac VYNSAVRSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGK
>BCO2_tarSyr VYDSIARSCPRRFVLPLNVSLNAPEEENLSPLSYSSATAVKKTDGK
>BCO2_otoGar VYNSAARSFPRRFVLPLNVGLNAPEGENLSPLSYSSASAVKQADGK
>BCO2_tupBel VYNSVARSFPRRFVLPLGVSSNAPEGENLSPLSYSSASAVKLSDGK
>BCO2_musMus VYELKAKSFPRRFVLPLDVSVDAAEGKNLSPLSYSSASAVKQGDGE
>BCO2_ratNor VYKAKAKSFPRRFVLPLDISVGAPEGENLRPLPYSSASVVKQGDRE
>BCO2_cavPor VYRSVARSFPRRFVLPLDVTVNTPEGETLSPLSYSSASAVKQADGK
>BCO2_speTri VYNSAALSFPRRFVLPLHISENDPAGENLSPLSYSSASAVKQSDGK
>BCO2_oryCun VYNSVARSFPRRFVLPLNVSINAPEGKNLSPLTYSSASAVKQADGK
>BCO2_vicPac VYNSVARSFPRRFVLPLHVSLNAPERENLSPLSYSSASAVKQADGK
>BCO2_turTru VYNSVARSFPRRFVLPLHVGLNAPEGKNLSPLTYSSASAVKQADGK
>BCO2_bosTau VYNLIARNSPRRFVLPLLGNLNAPEGENLSPLTYSSASAVKQADGK
>BCO2_equCab VYNSAAKSFPRRFVLPLHVSLDAPEGKNLSPLSYSSASAVKQADGK
>BCO2_felCat VYNSVGRSFPRRFVLPLHVSLNDPEGQNLSPLSYSSASAVKQADGK
>BCO2_canFam VYNSVGRSFPRRFVLPLHVSLNDPEGENLSPLSYSSASAVKHADGK
>BCO2_myoLuc VYNSVATSFPRRFVLPLRVSLNAPEGENLSLLSYPSASAVKQADGK
>BCO2_pteVam VYNSVARSFPRRFVLPLHINLNAPEGENLSPLPYSSASAVKQADGK
>BCO2_eriEur VYNSVARSFPRRFVLPLNVNLDTPEEENLSPLSYSSASAVKQADGT
>BCO2_sorAra VYNSLARSFPRRFVLPLNISPNAPQGENLSSLSYSSASAVKQADGK
>BCO2_loxAfr VZISVARSFPQRFVVPLNVSLNAPEGQTLGLLSRSLASVVEQADGK
>BCO2_dasNov VYNSVARSFPRRFVLPLNVSLNAPEGENLSPLSYSSASAVK-ADG-
>BCO2_choHof VYNSVARSFPRRFVLPLDVSLNAPEGENLSSLSYSSASAVKQADGK
>BCO2_monDom VYNSVARAFPRRFVLPLDISTKASVGQNLSPLTYSSASAVKQADGT
>BCO2_ornAna VYNSAARTFPRRFVLPLDAFLDAPTGENLSPLTYSTAKAMRGEDGK
>BCO2_galGal IFGSVARTFPRRFVLPLKVNSDTPVGKNLNPLSYTSAKAVKDSDGK
>BCO2_galLaf IFGSVARTFPRRFVLPLNVNSDTPVGKNLNPLSYTSAKAVKDSDGK Gallus lafayetii
>BCO2_taeGut ---------------------------------------------- finch trace coverage unavailable
>BCO2_anoCar TYNSIATPYPRRFVLPLNIDDKKPVGENLSPLSYTSATAVKEADGK
>BCO2_tetNig VYNSTGRAFPRRFVLPLHVTSQTAAGHNLNTRPZSKETCVKTDKDT
>BCO2_takRub VYNSTGRAFPRRFVLPLHVTSEMATGQNLNTRASSQATCVKTGKDT
>BCO2_gasAcu VYNTLCRVFPRRFVLPLNVDQETPYGRNLN--PKGSATSVRFAKNK
>BCO2_oryLap VYNTTERSFPRRFVLPLNLTSETPTNQNLNTRPFSKASCTKISPDK
>BCO2_danRer FFNSLCTNLPRRYVLPLEVKEDEPNDQNLINLPYTTASAVKT-QTG
                              *

Reference gene collection: non-teleosts

Here the primary focus is obtaining reliable full length genes for the three members of this gene family from early diverging species (rather than standard teleost sequences more closely related to human), the idea being to possibly correlate gene expansions of the RPE65 family with the origin of imaging vision in deuterostomes. However partial sequences are also of valuable for purposes of establishing paralog numbers and presence.

Here it must be immediately noted that many Gnomon predicted sequences at GenBank are so deeply flawed that their uncritical use would hopelessly taint any comparative genomics effort. Without transcripts and given the rates of divergence, it is quite difficult to recover full length genes by blast into incomplete and sometimes garbled assemblies. Of the early deuterostome invertebrates, only Ciona has an adequate (tileable) set of transcripts vis-a-vis this gene family. Yet tunicates have lost one family member altogether, BCO2.

This gene family is quite unusual in that new members are quite difficult to classify by blast clustering relative to a reference collection. The match qualities tend to be quite similar, possibly attributable to gap issues and regions of uncertain and unpersuasive alignment. Here it is best to classify by individual exons because each paralog is intronated distinctively.

Because intronation patterns are strongly conserved from human back to pre-bilaterans (eg cnidarian and placamorpha), the fact that the three paralogs are intronated quite differently implies gene duplication and divergence occured very early, prior to the main era of intron establishment in early pre-metazoan eukaryotes. This is consistent with full length counterparts with conserved 3D structure already existing in bacteria.

This in turn implies that loss of one or more family members has occured in many lineages. For example, arthropods (notably many insect species) contain but a single gene copy (denoted NinaB), lophotrochozoan genomes have none (despite ciliary opsins), and tunicates have two. Gene expansions have also occured in species such as Nematostella yet no expansion occured in deuterostomes despite supposed 1R and 2R whole genome expansions.

>RPE65_homSap length=547 14 exons
0 MSIQ 21 VEHPAGGYKKLFETVEELSSPLTAHVT 1
2 GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR 2
1 FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR 2
1 FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ 0
0 VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA 1
2 DKEDPISKSEIVVQFPCSDRFKPSYVHS 21 FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG 0
0 VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG 21 FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK 0
0 ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ 1
2 AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR 0
0 LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD 1
2 GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS* 0

>BCMO1_homSap length=547 11 exons 51,666 bp
0 MDIIFGRNRKEQLEPVRAKVT 1
2 GKIPAWLQGTLLRNGPGMHTVGESRYNHWFDGLALLHSFTIRD 1
2 GEVYYRSKYLRSDTYNTNIEANRIVVSEFGTMAYPDPCKNIFSK 2
1 AFSYLSHTIPDFTDNCLINIMKCGEDFYATSETNYIRKINPQTLETLEK 0
0 VDYRKYVAVNLATSHPHYDEAGNVLNMGTSIVEKGKTKYVIFKIPATVP 1
2 EGKKQGKSPWKHTEVFCSIPSRSLLSPSYYHSFGVTENYVIFLEQPFRLDILKMATAYIRRMSWASCLAFHREEK 0
0 TYIHIIDQRTRQPVQTKFYTDAMVVFHHVNAYEEDGCIVFDVIAYEDNSLYQLFYLANLNQDFKENSRLTSVPTLRRFAVPLHVDK 0
0 NAEVGTNLIKVASTTATALKEEDGQVYCQPEFLYE 1
2 GLELPRVNYAHNGKQYRYVFATGVQWSPIPTK 0
0 IIKYDILTKSSLKWREDDCWPAEPLFVPAPGAKDEDD 1
2 GVILSAIVSTDPQKLPFLLILDAKSFTELARASVDVDMHMDLHGLFITDMDWDTKKQAASEEQRDRASDCHGAPLT* 0

>BCO2_homSap length=579 12 exons alt leader peptide not shown
0 MGNTPQKKAVFGQCRGLPCVAPLLTTVEEAPRGISARVWGHFPKWLNGSLLRIGPGKFEFGKDK 2
1 YNHWFDGMALLHQFRMAKGTVTYRSKFLQSDTYKANSAKNRIVISEFGTLALPDPCKNVFERFMSRFELPGKAA 1
2 AMTDNTNVNYVRYKGDYYLCTETNFMNKVDIETLEKTEK 0
0 VDWSKFIAVNGATAHPHYDLDGTAYNMGNSFGPY 1
2 GFSYKVIRVPPEKVDLGETIHGVQVICSIASTEKGKPSYYHSF 1
2 GMTRNYIIFIEQPLKMNLWKIATSKIRGKAFSDGISWEPQCNTRFHVVEKRTGQ 0
0 LLPGRYYSKPFVTFHQINAFEDQGCVIIDLCCQDNGRTLEVYQLQNLRKAGEGLDQ 0
0 VHNSAAKSFPRRFVLPLNVSLNAPEGDNLSPLSYTSASAVKQADGT 0
0 IWCSHENLHQEDLEKEGGIEFPQIYYDRFSGKKYHFFYGCGFRHLVGDSLIKVDVVNKTLK 0
0 VWREDGFYPSEPVFVPAPGTNEEDGGVILSVVITPNQ 0
0 NESNFILVLDAKNFEELGRAEVPVQMPYGFHGTFIPI* 0

>BCDO2_galGal 67% identical homSap, FVLPLK yellow SNP, RefSeq XM_417929 in error
0 MQFVPGLKNSLPSPLEEQFTLPTLQCISPLLQTVEETPEPIPAKIKGHIPGWINGNLLRNGPGKFEFGEEK 2
1 YNHWFDGMALLHQFQLRNGTVTYQSKFLQSNSYLINNQHNRIVVSEFGTLAMPDPCKSVFARFMSRFDPP 1
2 PSDNANVSYVVYKGDYYVTGENNCMYKVDPETLEMKEK 0
0 VDWTKFVAVNGATAHPHYAPDGTAYNMGNSYGKF 1
2 GTTYNIIEVPPQKSNCNETLEGAKVLCSIAPTDNMKPSYYHSF 1
2 GMSENYIIFIEQPIKLNLLRIITSKFRGKPISEGINWEPQYNTRFHVVDKRTGK 0
0 VLPGQWYTKPFVTFHQINAFEDRGCVVLDLCCQDDGKTLAVYKLQNMRKSGADLDQ 0
0 IFGSVARTFPRRFVLPLKVNSDTPVGKNLNPLSYTSAKAVKDSDGK 0
0 VWCTHENLHPDGFENFGGLEFPQINYSQYSGRKYRYFYGCGFRHFIGDSLMKVDVETKNFK 0
0 IWQEDGSYPSEPVFVPVPNATAEDSGVILSVVISPDE 0
0 NRSAFLLVLDAETFRELGRAEVPVQMPYGFHGIFSSR* 0

>RPE65_cioInt 40% but about equally similar, slightly different intronation
0 MFAIQRRPFFAVFRNFNKMSAPSKTKSYVKLLQKAEERANAECVVT 1
2 GCIPEWLNGDVLRNGPAEFDIGPDTFKHWFDGHALLHK 2
1 FSMFEGKVTYSSKFLRSGTYKTNHENSRIIIGEFGTASRPDPCKNMFSR 2
1 FFTNFVEIAPRSDNANVSVAQLGEAYYAITDGPTAYGFDPETLETKNLITDCGPANMTVTAAHPHY 1
2 DRNGDYLNLGTTFGRTPHYHVIKVPAAKMTSPDPMNELEVFMKFPSTTSNASYHHS 2
1 FGLSENWIIFHEQPFSFSTPKLLIGLKLWNPILSSFYEDKQTIS 0
0 FHIINKTTGEKIATKYEARGMFCFHHINAYETKENDGKRFIVVDMCGSDRSLVWLL 2
1 GLDTLLDEEAHDKVVSNLDEKYLTRPRRIVIPLDISSDTPN 1
2 DTNLVTIPGCKATAMLNKSGVVSLTYELLVPDDFPNTELGIELPRINYDGYNGREYK 2
1 FIYAISSEYILPSHLVKINVETKEIKYWKEK 0
0 DKYTSEPIFVPRPGSQDEDDGVVLSTVISPTDDKTFLLILDGQSFKEIARAE 0
0 IETKMSYPLHGLFSK* 0

>BCMO1_cioInt 525 aa tiled transcripts agree with genomic
0 MDFPVSAFPHLTALATTKNIEYAEAVQGKVQ 1
2 GEVPSWLNGSWYRNGPGVVHFREESVKHWFDGMALARK 2
1 FCIEDGKVSYMSRLVDGESLQKNTAAGRVVVAEFGTTTHSEGFLGR 2
1 VKSALTMPEFTDNCLINFMNLGDHLFAITESNFIRQIDPVTLDTKDK 0
0 VDLAKHLPINIMSSHPLVDGEGNVYTFSSSIFNMGRTKYNLLKFPAAAP 1
2 GTPLETILSQSESICSIDSSWRVSPSYHHSFAMSEKYAVFVEMPLKIDIPKMAVAHLRHMCYSDCIEVLEDTK 0
0 TRIYLVNKETGKQHPITFLCDPLIVYHHVNAYDDGDHVVLDLSCYKKNSFYDKFTMSNLEKTPQEFSKLFDSDEQAVKAMRIVLPLANDS 0
0 KTTGNLVSVANTSCTAEFQGNNIFCTSEMLSVGTECAVINNKYIGKKYKYFYSPGGLKLPPGEM 0
0 LTKIDVETKQRVQTWQEKGCWASQPVFVAKPGATQEDE 1
2 GILMSSVVNENGNPFLLMLDAKSFTEVARIHFDANIPPDVHGVFVPKA* 0

Regularized reference gene collection: teleost RPE65

It is easy to compile large sets of bony vertebrate exons for these three genes using the 44-species genomic alignments at UCSC. To do this, look up the human gene by name at GeneSorter (or blat in a reference sequence) and click on "protein fasta" on the gene details page. Among the various output configurations provided, select all species checking the options as below. Note these alignments, being exon-aware, are intrinsically homological unlike blast alignments in gappy regions which lack this local constraint.

For some species, no data is available (shown as dashes). For others, some exons or parts of exons are misssing. This can be due to incompleteness of the respective genome or technical difficulties at exon edges due to split codons. To facilitate uniform comparison of paralogs, the output can be 'regularized' by filling in missing data using the nearest species in the taxonomic sense, for example using chicken data if finch is missing an exon. Most human genes can be completely regularized back to teleost fish. In some cases, notably frog, it may be necessary to stub in an orthologous region from salamander cDNA.

This introduces artefacts that have the effect of understating comparative genomics variability at the locus but that error is offset by the benefits of having 'complete' copies of the three genes in the same set of 44 species. As long as regularization is limited (topologically) to species diverging off the same node (eg lizard could regularize finch and chicken but not frog or platypus), the impact on gene history at the ancestral nodes leading to human will be very minimal. The regularized set works quite well in a blast classificatory tool.

The sequences for RPE65, BCMO1, and BCO2 have been completely regularized in this manner below. This allows comparison of variation by various techniques such as percent identity at nodes (ie averaging human matches to all species coming off that node if ancestral sequences are not computed) and residue-by-residue conservation by Multalin and similar tools.

Regularization can be done by hand in a spreadsheet using fill-down and similar commands. Begin by creating a template whose first column consists of the 44 species. Color rows by subclade as a visual assist to filling in using tree topology as constraint. Now copy the exons, replace all Z by *, replace double carriage returns by a placeholder, replace remaining carriage returns by tabs, replace placeholder with single carriage return, place into spreadsheet, and reverse rows and columns. Now each column is a separate exon and guided regularization can begin.

Differance alignment of RPE65 relative to homSap:

hg18_1_  MSIQVEHPAGGYKKLFETVEELSSPLTAHVTGRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRRFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQVDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQADKEDPISKSEIVVQFPCSDRFKPSYVHSFGLTPNYIVFVETPVKINLFKFLSS
gorGor1  ...........................................................................................................................................................................................................................................................................
ponAbe2  ...........................................................................................................................................................................................................................................................................
rheMac2  ...........................................................................................................................................................................................................................................................................
calJac1  ...........................................................................................................................................................................................................................................................................
panTro2  ...........................................................................................................................................................................................................................................................................
tarSyr1  ..V.......................P..I.................................................................................................I.......I..............Y.................................S.......................................V..........................................
oryCun1  .......................................................................................................................................I................................................S.......................................V..........................................
ochPri2  .................................................................................K.....................................................I................................................S.......................................V..........................................
equCab2  .......................................................................................................................................I..................V.............................S.......................................V..........................................
felCat3  .......................................................................................................................................I................................................S.......................................V..........................................
vicPac1  .......................................................................................................................................I...................................................................................................................................
bosTau4  ..S....................................................................................................................................I..................V................................................................................................................
turTru1  .......................................................................................................................................I...................................................................................................................................
micMur1  ..........................M...........S................................................................................................I................................................S..................................................................................
speTri1  ...................................V....................................................................................................................................................S..................................................................................
tupBel1  .........A............................S................................................................................................I................................................S...............................D..................................................
canFam2  ................................................................................................................................................................................................................................V....................................L.....
myoLuc1  ...............Y.........V.........F...........................................................................................I.......I................................................S.......................................V..........................................
eriEur1  ..A..............................V.....................................................................................................I..................V.............................S................V......................V.......................F..................
sorAra1  ..A................................V.I........S........................................................................................I......................................................................I.........................................F..................
cavPor3  .........S..R....................V...................A.........................Y.........................Y.Y...........................I.................R....................................................I............................................................
pteVam1  .........S.....................................................................Y.........................Y.....................I........................................................S..................................................................................
loxAfr2  ...............................................................................................N...........................K...........I................................................S...............................Q.......V..........................................
proCap1  ...........................................................................................................................K...I.......I................................................S...............................Q..................................................
echTel1  ....M.................................S............................................................L...........................I.......I..............L...V.............................S...............................Q.......V..........................................
dasNov2  ....I............................................................................K.................L...................................I................................................S...................................N...V..........................................
choHof1  ....I............................M...............................................K.................L...................................I................................................S...................................N...V.........................................V
otoGar1  ..M...................................S.........................................................................R......................I..................V.............................S.......................................V..........................................
dipOrd1  ....I..................T.........................................................K.........................................K...........I.................................K..............S.......................................V.....................S....................
mm9_1_1  ....I......................................................................................................................K...........I...................................I............S...............TV....I.....K.......N...V..........................................
rn4_1_1  ....I..................T.......................................................Y.K.........................................K...........I................................................S...............TV....I.....K.......N...V..........................................
ornAna1  ..N................................V.............................................K.................L...................................I...................................I.I..M.......................A...................N...V...............................I..........
monDom4  ..H.......................P...R....P..A..................................D.R.......................L...................................I...................................I.I..M.......................A..................MN...V.........L..........................L.....
galGal3  ..S...............A......V.........T..R...........................................VG.....................Y.Y...............K.................................D...........K............V..................L....IR...........MN...V....................................L.....
taeGut1  ..S...............A......V.........T..R............................................V.....................Y.Y............T..K.............................R...D..........SK...............................L....IR............N...V....................................L.....
anoCar1  ..S...................AT.I.T.......V..R...............................EI.......Y.......C....I............Y.Y............T..Q..................F........L.....DN...L.K..ISKI.....V..............................R.......RK..MT.C.V........................L...........L.....
xenTro2  .TNH..............A...AT.MAT.....V.P..S................Q..............EIR....S.....V.....................F.Y....R..........K.L........................Y...V.......V.K......I.I..V.......S...............A....V..T...........T..TV...................M....L....Q......L....A
tetNig1      ..........I.......DE.VA.KIS.TL.A..S.....M........D...R........I....L.........K.............N.V....L..A.Y............T..K.......CM..I.TI...F..V........VD.DS...L.K...SK.L....V.....KDA..............M.L.........A.K.SLE.FE.ARV...L.S.E.L....I....MSD..F....P......I....A
fr2_1_1      .....A....I.......NE.IA.TIS.V..T..S.....M........DQ.LH........I....L.D.R...Y.K.............N.V.......A.Y............T..K.I.....C...I.TI...F..V........VD.DS...L.K...SK......I.....KDP..............M.L.........APK.SLE.FE.ARV...L.S.E.L....I....M.E..F....P......L....A
gasAcu1      .....A....I.......NE.IP.R.I.VL.S..G.....M........G...N........I....L.N.Q...Y.K.....T.......N.V.......A.Y............T..K.I.....C...IC.I...F..V....Y...VD.DS...L.K....K......V.....TDA................L.........P.E..S..LERAQV.L.L.S.E.L....L....M.D.HF....Q.....VL.Y..A
oryLat2      .....A....I.......DE.IP.QIS.V..S..G.....M........D...H........M....LRN.Q...N.K..K..S.......N.V.......I.Y...............K.I.....C...I..I...F..V....Y...VD.DS...LEK..V.K.L....L.......A.............DM.L.........A.K..S...E..Q....L.S.E.L.........M.N..F....Q......L....A
danRer5      L.........V..SC...AE.IP...S.E..A..S.....M........D.................L.D.R.....................V.......T.Y............T..Q.I.....C...I..I...F...........VD.D....V.K......L....L.......A..............M.L...........E..S.QFE..K.L....S.E...........I.E.HF...........L...T.

hg18_1_  WSLWGANYMDCFESNETMGVWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDKADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQAFEFPQINYQKYCGKPYTYAYGLGLNHFVPDRLCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS
gorGor1  ..........................................................................................................................................................................................................................................................................
ponAbe2  ..........................................................................................................................................................................................................................................................................
rheMac2  ....................................................................................................................I.....................................................................................................................................................
calJac1  ................................F...........................................................................................................................R................................I............................................................................
panTro2  ...............................................................................................................................................-..........................................................................................................................
tarSyr1  .............................R..............................................................................................................................R................................I............................................................................
oryCun1  .............................R......................E.D...................................................F................D..........................L........G..........................................................................................................
ochPri2  .............................R........................D..V.................................................................D...................................G..........................................................................................................
equCab2  .............................R..........S...........E.E........................................................................................................G..........................................................................................................
felCat3  .............................R..........S...........E.E........................................................................................................G..........................................................................................................
vicPac1  ......................................................E........................................................................................................G..........................................................................................................
bosTau4  ................................I....................HE........................................................................................................G..........................................................................................................
turTru1  ................................I....................SE..V.............................R..................T....................................................G..........................................................................................................
micMur1  .............................R.........................................................................................S.......................................G.......................................................................................................R..
speTri1  .....T...............................................RE........................................................................................................G....................................N................................................I...................P
tupBel1  .............................R..........S.............E..V.....................................................................................................G.....F.............................................................T......................................
canFam2  ........................................S.............E.......................................................................T.R..............................G..........................................................................................................
myoLuc1  .......................V.....R........................E...................................S............................S......................A................G......T..........................................E.................T......................................
eriEur1  .......................V.....R....................F...E..................................................T.............S.............V.........................G.............................I.I....E..........................I...T......................................
sorAra1  .......................V.....R....................F...E.......................................................N.............................................RT.G...................................A..........A................I...T......................................
cavPor3  .....T...............................................RE...................................S....................................................................G....................................N..............................P.....S..................V............A
pteVam1  .......................V.....R....................F...E...................................S..........................S.........................................G....................................Y.......................................................V.............
loxAfr2  .....-D.........N............R..........S.....................................................................................................A................S...................................A.............E.MD........I............................................
proCap1  .....-D.........N............R..........S.....................................................................................................A................S...................................A.............E.MD........I............................................
echTel1  .............................R..........S..................................................................N..................................A................S...................................A.............E.MD........I............................................
dasNov2  ........L....................RM.........S...............V..................................................N..................................A................S...................................A.............E.MD.......................V.............................
choHof1  .............................RM.........S...............V..................................................N..................................A................S...................................A.............E.MD.....................................................
otoGar1  ................S............R..I....................S..........................G..D....S................SM.............H.....V....D...........................G.R.......................R................................I........P........V.............................
dipOrd1  .....................I...H.RQR..........S............D......................S..........R.......................................................................G....................................N................................................I...................P
mm9_1_1  ................S......V.....R..F......................................................R..M..............T...V...R......H.....T.R.............................FG..................K...M......I.M...............Q............................V........I......T...........R.
rn4_1_1  ................S......V.....R..F......................................................R..M..............T.......R......H.....................................CG..................K..........I.M...............Q............................V........I......T............P
ornAna1  .......................V...NQGRC..H.....S..............................................R..K................T.........S..Y......................................G......T.....................D...................................N..P..............M....................R..
monDom4  .T.....................V.....G..........S...........EDN................................R..K..............A.N.........S......A..................................G....AF...................V.....L.H.................Q.....................C..V.....MT........T..........RR.
galGal3  .......................V.E..KGRL..I.....A.........F...........T.................A..D....Q.E......A.......R..............Y.....T.R....V......I.....H.........K..G......T......................................................I.I...S.P............M.........V...........RA
taeGut1  .......................V.E..KGRL..L.F...A.....................T.................A..D...RQ.E......A.......S..............Y.....T.R...........I.....H.........T..G......T..............................A.......................I.I...S.P............M.........V...........RA
anoCar1  ................S....M.V....KG....I.................E.........T...Y..I..........D.......H.Q................E........I.........T.N...........I...............T..S.....F................I.I..R.........A.......................II....N.P........S...M........D.........F...A
xenTro2  ..I...........H......M.V.E.HTGE...I.....A..I..............L.V........I..................H.E......A.......D.N.N.V.....S.NY.....T.H..G........................K..G..D.S..........I....T...............NA........QA...I.....I...A.I..AV.H..S.....D...M..I.....DTI.......M..RA
tetNig1  ..IR..T..........L.T.F.L.T.DPAD.SSY.F...A..I.........Q..MV....T...H........V....QE......A.M..............D.SSE.L.....S.SY.....V.RR.G..............L.........SE.S..M.HFT........I....M....Q....QE.R.EEC.....L..PT.G.TD.....L.....K...--R.GF..V.D..T...LG....SV.....L..M..LT
fr2_1_1  ..VR..T..........L.T.F.L.T.DPAD.SSY.F...A..V.......K.QD.IV....T...........W.....A..D....A.MM..........I..DVH.E.M.....S.SY.....V.R..G..............H.........SE.S..M.RF.F.......I....M....Q...MRE.R.EEC.....L..AT.G.TD.....L.....K...--R.GS..V.D..T.T..G....SV.....L..M..LT
gasAcu1  ..VR.TT........DS..T.F.L.T.DPAD.SSY.F...A..I.....A...Q..IV....T...HD...D.......KGE......A.MR.............D.HREEQ.R...S.SY.....A.R..G........................SLCR..K.SF.........I...VV....Q.........DEC.....L..PT.A.T......L..I..K...--R.SF..V.D.VK.T.L.....NTI....L..TY.LT
oryLat2  ..IR.TT.......C.S..T.F.LTT.NPAA.SSH.F...A............Q..IV....T...H..............E......A.SR.............D.Y.EEQ.....S.SY.....V....G........................SQC...K.FF.........I...VV....Q.........E.C........AT.G.TQ.....L..I..K..T--R.GF..V.D.MK.T.......NAI....L...Y.MT
danRer5  ..IR.S.........DK..T.F.L.A.NPG..IDH.F...A..I.....CF..Q..IV....T...H.............Q.......A.LR.............D.HREEQ.....S..Y.....VMR..G.V......................S.FN..D..F.............F......S....I.....A.....L..QS...ED.....L..I..K...--R..F....K.T..T.I.....DVL..L.L..IYTLT

>RPE65_homSap Homo sapiens (human)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_panTro Pan troglodytes (chimp)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFS-PRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_gorGor Gorilla gorilla (gorilla)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_ponPyg Pongo pygmaeus (orang_sumatran)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_macMul Macaca mulatta (rhesus)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLITLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_calJac Callithrix jacchus (marmoset)
MSIQ
vEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_tarSyr Tarsius syrichta (tarsier)
MSVQ
VEHPAGGYKKLFETVEELSSPLPAHIT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNYITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_micMur Microcebus murinus (mouse_lemur)
MSIQ
VEHPAGGYKKLFETVEELSSPLMAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLSNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFRKS*

>RPE65_otoGar Otolemur garnettii (bushbaby)
MSMQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCRNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHIADKKRRKYINNKYRTSPFNLFHHINTYEDSGFLIVDLCCWKG
FEFVYNYLYLANLRGNWDEVKKSARKAPQPEVRRYVLPLSMDK
ADTGKNLVTLPHTTATAVLCSDDTIWLEPEVLFSGPRQ
AFEFPQINYQKYGGRPYTYAYGLGLNHFVPDR
LCKLNVRTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVILSVVVSPGPGQKPAYLLVLNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_tupBel Tupaia belangeri (tree_shrew)
MSIQ
VEHPAAGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKDDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNEFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTFAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_musMus Mus musculus (mouse)
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISVNGATAHPHIESDGTVYNIGNCFGKNFTVAYNIIKIPPLKA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHVADKKRRKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAMKAPQPEVRRYVLPLTIDK
VDTGRNLVTLPHTTATATLRSDETIWLEPEVLFSGPRQ
AFEFPQINYQKFGGKPYTYAYGLGLNHFVPDK
LCKMNVKTKEIWMWQEPDSYPSEPIFVSQPDALEEDD
GVVLSVVVSPGAGQKPAYLLVLNAKDLSEIARAEVETNIPVTFHGLFKRS*

>RPE65_ratNor Rattus norvegicus (rat)
MSIQ
IEHPAGGYKKLFETVEELSTPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYYRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFTVAYNIIKIPPLKA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHVADKKRRKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAMKAPQPEVRRYVLPLTIDK
ADTGRNLVTLPHTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKCGGKPYTYAYGLGLNHFVPDK
LCKLNVKTKEIWMWQEPDSYPSEPIFVSQPDALEEDD
GVVLSVVVSPGAGQKPAYLLVLNAKDLSEIARAEVETNIPVTFHGLFKKP*

>RPE65_dipOrd Dipodomys ordii (kangaroo_rat)
MSIQ
IEHPAGGYKKLFETVEELSTPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCKYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTSNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWIHIAHKRQRKYLNNKYRTSSFNLFHHINTYEDDGFLIVDLCCWKG
FEFVYNYLYLSNLRENWEEVKRNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEIARAEVEINIPVTFHGLFKKP*

>RPE65_cavPor Cavia porcellus (guinea_pig)
MSIQ
VEHPASGYRKLFETVEELSSPLTAHVT
GRVPLWLTGSLLRCGPGLFEVGAEPFYHLFDGQALLHKFDFKEGHVTYYRR
FIRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITRINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIIKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGTNYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDREFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNASKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGPGQKPASLLILNAKDLSEVARAEVEVNIPVTFHGLFKKA*

>RPE65_speTri Spermophilus tridecemlineatus (squirrel)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPVWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGTNYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDREFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEIARAEVEINIPVTFHGLFKKP*

>RPE65_oryCun Oryctolagus cuniculus (rabbit)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEENDFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNFDK
ADTGKNLVTLPNTTDTAILCSDETIWLEPEVLFSGPRQ
aFELPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_ochPri Ochotona princeps (pika)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNDFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTDTAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_vicPac Vicugna pacos (lama)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_turTru Tursiops truncatus (dolphin)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYINNKYRTSPFNLFHHINTYEDSEFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNARKAPQPEVRRYVLPLNTDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_bosTau Bos taurus (cow)
MSSQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYINNKYRTSPFNLFHHINTYEDHEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_equCab Equus caballus (horse)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEENEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_felCat Felis catus (cat)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEENEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_canFam Canis familiaris (dog)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSSFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATATLRSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_myoLuc Myotis lucifugus (microbat)
MSIQ
VEHPAGGYKKLYETVEELSSPVTAHVT
GRIPFWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHkFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNASKAPQPEVRRYVLPLNIDK
ADTGKNLVTLSNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYGGKPYTYTYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPEALEEDD
GVVLSVVVSPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_pteVam Pteropus vampyrus (macrobat)
MSIQ
VEHPASGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYYRR
FIRTDAYVRAMTEKRIVITEFGTYAFPDPCKNIFSR
FFSYFRGVEITDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNASKAPQPEVRRYVLPLNIDK
ADTGKNLVSLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPYSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEVNIPVTFHGLFKKS-

>RPE65_eriEur Erinaceus europaeus (hedgehog)
MSAQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRVPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSVAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNFIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLTIDK
ADTGKNLVTLSNTTATAILCSDETVWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWIWQEPESYPSEPIFVSHPDALEEDD
GVVLSVVISPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_sorAra Sorex araneus (shrew)
MSAQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPVWITGSLLRCGSGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIIKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNFIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ANTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRTYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVAHPDALEEDD
GVVLSVVISPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_loxAfr Loxodonta africana (elephant)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTENRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKQDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWG-DYMDCFESNENMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_proCap Procavia capensis (hyrax)
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEITDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKQDPISKSEIVVQFPCSDRFKPSYVHs
FGLTPNYIVFVETPVKINLFKFLSSWSLWG-DYMDCFESNENMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
GVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_echTel Echinops telfairi (tenrec)
MSIQ
MEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNLITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKQDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNINK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
GVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_dasNov Dasypus novemcinctus (armadillo)
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYLDCFESNETMG
VWLHIADKKRRMYLNNKYRTSSFNLFHHINTYEDNGFVIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNINK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSVVVSPGAGQKPAYLLVLNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_choHof Choloepus hoffmanni (sloth)
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
GRMPLWLTGSLLRCGPGLFEvGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSVWSLWGANYMDCFESNETMG
VWLHIADKKRRMYLNNKYRTSSFNLFHHINTYEDNGFVIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNINK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65_monDom Monodelphis domestica (opossum)
MSHQ
VEHPAGGYKKLFETVEELSSPLPAHVR
GRIPPWLAGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKDGRVTYHRR
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISINGMTAHPHIENDGTVYNIGNCFGKNFAIAYNIVKIPPLQA
dKEDPMNKSEVVVQFPCSDRLKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWTLWGANYMDCFESNETMG
VWLHVADKKRGKYLNNKYRTSSFNLFHHINTYEEDNFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAKKAPQPEVRRYVLPLAINK
ADTGKNLVSLPNTTAAAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYAFAYGLGLNHFVPDR
LCKLNVVTKETWLWHEPDSYPSEPIFVSHPDAQEEDD
GVVLSVVVSPGAGQKPACLLVLNAKDMTEVARAEVETNIPVTFHGLFRRS*

>RPE65_ornAna Ornithorhynchus anatinus (platypus)
MSNQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPVWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISINGMTAHPHIENDGTVYNIGNCFGKNFAIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPIKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKNQGRCLNHKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAKKAPQPEVRRYVLPLNITK
ADTGKNLVSLPYTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYTYGLGLNHFVPDR
LCKLNVKTKDTWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVNPGPGQKPAYLLILNAKDMSEVARAEVEINIPVTFHGLFRKS*

>RPE65_galGal Gallus gallus (chicken)
MSSQ
VEHPAGGYKKLFETAEELSSPVTAHVT
GRIPTWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
VGRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFSYFKGVEVTDNALVNVYPVGEDYYACTETNFITKINPDTLETIKQ
VDLCKYVSVNGATAHPHVENDGTVYNIGNCFGKNFSLAYNIIRIPPLQA
DKEDPMNKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHVAEKKKGRLLNIKYRTSAFNLFHHINTFEDNGFLIVDLCTWKG
FEFVYNYLYLANLRANWDEVKKQAEKAPQPEARRYVLPLRIDK
ADTGKNLVTLPYTTATATLRSDETVWLEPEVIFSGPRH
AFEFPQINYKKYGGKPYTYTYGLGLNHFVPDR
lCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSIVISPGSGPKPAYLLILNAKDMSEVARAEVEVNIPVTFHGLFKRA*

>RPE65_taeGut Taeniopygia guttata (finch)
MSSQ
VEHPAGGYKKLFETAEELSSPVTAHVT
GRIPTWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FVRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFTYFKGVEVTDNALVNVYPVGEDYYACTETNFITRINPDTLETIKQ
VDLSKYVSVNGATAHPHIENDGTVYNIGNCFGKNFSLAYNIIRIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHVAEKKKGRLLNLKFRTSAFNLFHHINTYEDNGFLIVDLCTWKG
FEFVYNYLYLANLRANWDEVKRQAEKAPQPEARRYVLPLSIDK
ADTGKNLVTLPYTTATATLRSDETIWLEPEVIFSGPRH
AFEFPQINYTKYGGKPYTYTYGLGLNHFVPDR
lCKLNVKTKETWVWQEPDAYPSEPIFVSHPDALEEDD
GVVLSIVISPGSGPKPAYLLILNAKDMSEVARAEVEVNIPVTFHGLFKRA*

>RPE65_anoCar Anolis carolinensis (lizard)
MSSQ
VEHPAGGYKKLFETVEELATPITTHVT
GRIPVWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFEIKEGHVTYYRR
FIRTDCYVRAITEKRIVITEFGTYAYPDPCKNIFSR
FFTYFQGVEVTDNALVNVYPVGEDFYACTETNFLTKINPDNLETLKK
VDISKIVSVNGVTAHPHIENDGTVYNIGNCFGKNFSIAYNIVRIPPLQA
DRKDPMTKCEVVVQFPCSDRFKPSYVHS
FGLTPNYLVFVETPVKINLLKFLSSWSLWGANYMDCFESNESMG
VWMHVADKKKGKYLNIKYRTSPFNLFHHINTYEENGFLIVDLCTWKG
YEFIYNYLYLANLRDNWEEVKKHAQKAPQPEVRRYVLPLNIEK
ADTGKNLITLPNTTATATLNSDETIWLEPEVIFSGPRQ
AFEFPQINYTKYSGKPYTFAYGLGLNHFVPDR
lCKINIKTRETWVWQEPDAYPSEPIFVSHPDALEEDD
GVVLSIIVSPGNGPKPAYLLILSAKDMSEVARAEVDINIPVTFHGFFKKA*

>RPE65_xenTro Xenopus tropicalis (frog)
MTNH
VEHPAGGYKKLFETAEELATPMATHVT
GRVPPWLSGSLLRCGPGLFEVGSEQFYHLFDGQALLHKFEIREGHVSYHRR
FVRTDAYVRAMTEKRIVITEFGTFAYPDPCRNIFSR
FFSYFKGLEVTDNALVNVYPVGEDYYACTETNYITKVNPETLETVKK
VDLCNYISINGVTAHPHIESDGTVYNIGNCFGKNFAIAYNVVKTPPLQA
DKEDPITKSTVVVQFPCSDRFKPSYVHS
FGMTPNYLVFVEQPVKINLLKFLSAWSIWGANYMDCFESHETMG
VWMHVAEKHTGEYLNIKYRTSAFNIFHHINTYEDNGFLILDVCCWKG
FEFIYNYLYLANLRENWEEVKKHAEKAPQPEARRYVLPLDINK
NDVGKNLVSLNYTTATATLHSDGTIWLEPEVLFSGPRQ
AFEFPQINYKKYGGKDYSYAYGLGLNHFIPDR
lTKLNVKTKETWVWQEPNAYPSEPIFVQAPDAIEEDD
GIVLSAVISPAVGHKPSYLLILDAKDMSEIARAEVDTIIPVTFHGMFKRA*

>RPE65_tetNig Tetraodon nigroviridis (pufferfish)
----
VEHPAGGYKKIFETVEELDEPVAAKIS
GTLPAWLSGSLLRMGPGLFEVGDEPFRHLFDGQALIHKFDLKEGHVTYHRK
FIRTDAYVRAMTENRVVITELGTAAYPDPCKNIFSR
FFTYFKGVEVTDNCMVNIYTIGEDFYAVTETNFITKVDPDSLETLKK
VDLSKYLSVNGVTAHPHKDADGTVYNIGNCFGKNMSLAYNIVKIPPAQK
DSLEPFEKARVVVQLPSSERLKPSYIHS
FGMSDNYFVFVEPPVKINLIKFLSAWSIRGATYMDCFESNETLG
TWFHLATKDPADYSSYKFRTSAFNIFHHINTYEDQGFMVVDLCTWKG
HEFVYNYLYVANLRQEWEEVKKAAMKAPQPEVRRYVLPLDISS
EDLGKNLVSLSYTTATAVLRRDGTIWLEPEVLFSGPRL
AFEFPQINYSEYSGKMYHFTYGLGLNHFIPDR
LMKLNVQTKETQEWREEECYPSEPLFVPTPGATDEDD
GVLLSVVVKPGA--RPGFLLVLDAKTLSELGRAEVSVNIPVTLHGMFKLT*

>RPE65_takRub Takifugu rubripes (fugu)
----
VEHPAAGYKKIFETVEELNEPIAATIS
GVIPTWLSGSLLRMGPGLFEVGDQPLHHLFDGQALIHKFDLKDGRVTYYRK
FIRTDAYVRAMTENRVVITEFGTAAYPDPCKNIFSR
FFTYFKGIEVTDNCLVNIYTIGEDFYAVTETNFITKVDPDSLETLKK
VDLSKYVSVNGITAHPHKDPDGTVYNIGNCFGKNMSLAYNIVKIPPAPK
DSLEPFEKARVVVQLPSSERLKPSYIHS
FGMTENYFVFVEPPVKINLLKFLSAWSVRGATYMDCFESNETLG
TWFHLATKDPADYSSYKFRTSAFNVFHHINTYKDQDFIVVDLCTWKG
FEFVYNYLWLANLRANWDEVKKAAMMAPQPEVRRYVIPLDVHK
EDMGKNLVSLSYTTATAVLRSDGTIWLEPEVLFSGPRH
AFEFPQINYSEYSGKMYRFAFGLGLNHFIPDR
lMKLNVQTKEMREWREEECYPSEPLFVATPGATDEDD
GVLLSVVVKPGA--RPGSLLVLDAKTLTEVGRAEVSVNIPVTLHGMFKLT*

>RPE65_gasAcu Gasterosteus  aculeatus (stickleback)
----
VEHPAAGYKKIFETVEELNEPIPARVI
GVLPSWLGGSLLRMGPGLFEVGGEPFNHLFDGQALIHKFDLKNGQVTYYRK
FIRTDTYVRAMTENRVVITEFGTAAYPDPCKNIFSR
FFTYFKGIEVTDNCLVNICPIGEDFYAVTETNYITKVDPDSLETLKK
vDLCKYVSVNGVTAHPHTDADGTVYNIGNCFGKNFSLAYNIVKIPPPQE
DKSDPLERAQVVLQLPSSERLKPSYLHS
FGMTDNHFVFVEQPVKINVLKYLSAWSVRGTTYMDCFESNDSMG
TWFHLATKDPADYSSYKFRTSAFNIFHHINAYEDQGFIVVDLCTWKG
HDFVYDYLYLANLKGEWEEVKKAAMRAPQPEVRRYVLPLDIHR
EEQGRNLVSLSYTTATAALRSDGTIWLEPEVLFSGPRQ
AFEFPQINYSLCRGKKYSFAYGLGLNHFIPDR
VVKLNVQTKETWVWQEDECYPSEPLFVPTPAATEEDD
GVLLSIVVKPGA--RPSFLLVLDAVKLTELARAEVNTIIPVTLHGTYKlt*

>RPE65_oryLap Oryzias latipes (medaka)
----
VEHPAAGYKKIFETVEELDEPIPAQIS
GVIPSWLGGSLLRMGPGLFEVGDEPFHHLFDGQALMHKFDLRNGQVTYNRK
FIKTDSYVRAMTENRVVITEFGTIAYPDPCKNIFSR
FFSYFKGIEVTDNCLVNIYPIGEDFYAVTETNYITKVDPDSLETLEK
VDVCKYLSVNGLTAHPHIEADGTVYNIGNCFGKDMSLAYNIVKIPPAQK
DKSDPIEKSQIVVQLPSSERLKPSYVHS
FGMTNNYFVFVEQPVKINLLKFLSAWSIRGTTYMDCFESCESMG
TWFHLTTKNPAAYSSHKFRTSAFNLFHHINTYEDQGFIVVDLCTWKG
HEFVYNYLYLANLREEWEEVKKAASRAPQPEVRRYVLPLDIYK
EEQGKNLVSLSYTTATAVLCSDGTIWLEPEVLFSGPRQ
AFEFPQINYSQCCGKKYFFAYGLGLNHFIPDR
VVKLNVQTKETWVWQEEDCYPSEPIFVATPGATQEDD
GVLLSIVVKPGT--RPGFLLVLDAMKLTEVARAEVNAIIPVTLHGLYKMT*

>RPE65_danRer Danio rerio (zebrafish)
----
LEHPAGGYKKVFESCEELAEPIPAHVS
GEIPAWLSGSLLRMGPGLFEVGDEPFYHLFDGQALLHKFDLKDGRVTYHRR
FIRTDAYVRAMTEKRVVITEFGTTAYPDPCKNIFSR
FFTYFQGIEVTDNCLVNIYPIGEDFYACTETNFITKVDPDTLETVKK
VDLCNYLSVNGLTAHPHIEADGTVYNIGNCFGKNMSLAYNIVKIPPLQE
DKSDQFEKSKILVQFPSSERFKPSYVHS
FGITENHFVFVETPVKINLLKFLTSWSIRGSNYMDCFESNDKMG
TWFHLAAKNPGKYIDHKFRTSAFNIFHHINCFEDQGFIVVDLCTWKG
HEFVYNYLYLANLRQNWEEVKKAALRAPQPEVRRYVLPLDIHR
EEQGKNLVSLPYTTATAVMRSDGTVWLEPEVLFSGPRQ
AFEFPQINYSKFNGKDYTFAYGLGLNHFVPDR
FCKLNVKSKETWIWQEPDAYPSEPLFVQSPDAEDEDD
GVLLSIVVKPGA--RPAFLLILKATDLTEIARAEVDVLIPLTLHGIYTLt*