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 the illegimate gene name suggests, is a protein of 65 kdaltons found in the retinal pigment epithelium adjacent to photoreceptor layers.

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).

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 would 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 it is merely an 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 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. The other two 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.

The confused history of RPE65

RPE65 was the subject of recent studies with serious experimental and interpretive error, such as attributing its enzymatic activity to LRAT (ecithin:retinol acyl transferase), assigning palmitolyation to various cysteine residues that did not occur, and attributing its (non-passaging) membrane association to these lipids when in fact that is intrinsic, and misunderstanding enzyme mechanism.

While this never made sense in view of full-length alignment of RPE65 with its two well-studied paralogous carotenoid oxygenases, the most interesting aspect of the debacle is the light it sheds on the multi-year delay cycle in updates at primary hub databases such as RefSeq, SwissProt, and OMIM. None of these have been corrected 18 months later. It's not clear when they will ever be revisited. Consequently hundreds of derived databases such as UCSC perpetuate serious misunderstandings about this important but straighforward disease gene and the visual pigment cycle in vertebrates.

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.

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

>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.

>RPE65r_hg8
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_panTro
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFS-PRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_gorGor
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_ponAbe
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_rheMac
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLITLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_calJac
MSIQ
vEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_tarSyr
MSVQ
VEHPAGGYKKLFETVEELSSPLPAHIT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNYITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRKYCGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_micMur
MSIQ
VEHPAGGYKKLFETVEELSSPLMAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKg
-------------------------------------------
ADTGKNLVTLSNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFRKS*

>RPE65r_otoGar
MSMQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCRNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHIADKKRRKYINNKYRTSPFNLFHHINTYEDSGFLIVDLCCWKG
FEFVYNYLYLANLRGNWDEVKKSARKAPQPEVRRYVLPLSMDK
ADTGKNLVTLPHTTATAVLCSDDTIWLEPEVLFSGPRQ
AFEFPQINYQKYGGRPYTYAYGLGLNHFVPDR
LCKLNVRTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVILSVVVSPGPGQKPAYLLVLNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_tupBel
MSIQ
VEHPAAGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKDDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNEFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTFAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_mm9
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISVNGATAHPHIESDGTVYNIGNCFGKNFTVAYNIIKIPPLKA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHVADKKRRKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAMKAPQPEVRRYVLPLTIDK
VDTGRNLVTLPHTTATATLRSDETIWLEPEVLFSGPRQ
AFEFPQINYQKFGGKPYTYAYGLGLNHFVPDK
LCKMNVKTKEIWMWQEPDSYPSEPIFVSQPDALEEDD
GVVLSVVVSPGAGQKPAYLLVLNAKDLSEIARAEVETNIPVTFHGLFKRS*

>RPE65r_rn4
MSIQ
IEHPAGGYKKLFETVEELSTPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYYRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFTVAYNIIKIPPLKA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNESMG
VWLHVADKKRRKYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAMKAPQPEVRRYVLPLTIDK
ADTGRNLVTLPHTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKCGGKPYTYAYGLGLNHFVPDK
LCKLNVKTKEIWMWQEPDSYPSEPIFVSQPDALEEDD
GVVLSVVVSPGAGQKPAYLLVLNAKDLSEIARAEVETNIPVTFHGLFKKP*

>RPE65r_dipOrd
MSIQ
IEHPAGGYKKLFETVEELSTPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCKYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTSNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWIHIAHKRQRKYLNNKYRTSSFNLFHHINTYEDDGFLIVDLCCWKG
FEFVYNYLYLSNLRENWEEVKRNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEIARAEVEINIPVTFHGLFKKP*

>RPE65r_cavPor3
MSIQ
VEHPASGYRKLFETVEELSSPLTAHVT
GRVPLWLTGSLLRCGPGLFEVGAEPFYHLFDGQALLHKFDFKEGHVTYYRR
FIRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITRINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIIKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGTNYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDREFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNASKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGPGQKPASLLILNAKDLSEVARAEVEVNIPVTFHGLFKKA*

>RPE65r_speTri
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPVWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGTNYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDREFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPNSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEIARAEVEINIPVTFHGLFKKP*

>RPE65r_oryCun
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEENDFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNFDK
ADTGKNLVTLPNTTDTAILCSDETIWLEPEVLFSGPRQ
aFELPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_ochPri
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSPFNLFHHINTYEDNDFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTDTAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_vicPac
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_turTru
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYINNKYRTSPFNLFHHINTYEDSEFLVVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNARKAPQPEVRRYVLPLNTDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_bosTau4
MSSQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYINNKYRTSPFNLFHHINTYEDHEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_equCab
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEENEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_felCat3
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEENEFLIVDLCCWKG
---VYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_canFam
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRKKYLNNKYRTSSFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATATLRSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_myoLuc
MSIQ
VEHPAGGYKKLYETVEELSSPVTAHVT
GRIPFWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLH-FDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTYEDNEFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNASKAPQPEVRRYVLPLNIDK
ADTGKNLVTLSNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYGGKPYTYTYGLGLNHFVPDR
LCKLNVKTKETWVWQEPDSYPSEPIFVSHPEALEEDD
GVVLSVVVSPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_pteVam
MSIQ
VEHPASGYKKLFETVEELSSPLTAHVT
GRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYYRR
FIRTDAYVRAMTEKRIVITEFGTYAFPDPCKNIFSR
FFSYFRGVEITDNALVNVYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
-------------------------------------------
ADTGKNLVSLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEPYSYPSEPIFVSHPDALEEDD
GVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEVNIPVTFHGLFKKS-

>RPE65r_eriEur
MSAQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRVPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSVAYNIVKIPPLQA
DKEDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNFIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLTIDK
ADTGKNLVTLSNTTATAILCSDETVWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKEIWIWQEPESYPSEPIFVSHPDALEEDD
GVVLSVVISPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_sorAra
MSAQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPVWITGSLLRCGSGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIIKIPPLQA
DKEDPISKSEIVVQFPCSDRFKPSYVHS
FGLTPNFIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKKRRKYLNNKYRTSPFNLFHHINTFEDNEFLIVDLCCWKg
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ANTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYRTYGGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVAHPDALEEDD
GVVLSVVISPGTGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_loxAfr
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTENRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKQDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWG-DYMDCFESNENMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_proCap
MSIQ
VEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSR
FFSYFKGVEITDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
dKQDPISKSEIVVQFPCSDRFKPSYVHs
FGLTPNYIVFVETPVKINLFKFLSSWSLWG-DYMDCFESNENMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
GVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_echTel
MSIQ
MEHPAGGYKKLFETVEELSSPLTAHVT
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEITDNALVNIYPVGEDYYACTETNLITKVNPETLETIKQ
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKQDPISKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHIADKKRRKYLNNKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNINK
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
GVVLSIVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_dasNov
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
gRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSSWSLWGANYLDCFESNETMG
VWLHIADKKRRMYLNNKYRTSSFNLFHHINTYEDNGFVIVDLCCWKg
-------------------------------------------
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSVVVSPGAGQKPAYLLVLNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_choHof
MSIQ
IEHPAGGYKKLFETVEELSSPLTAHVT
GRMPLWLTGSLLRCGPGLFE-GSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
GRIPLWLSGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
VDLCNYVSVNGATAHPHIESDGTVYNIGNCFGKNFSIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLFKFLSVWSLWGANYMDCFESNETMG
VWLHIADKKRRMYLNNKYRTSSFNLFHHINTYEDNGFVIVDLCCWKg
-------------------------------------------
ADTGKNLVTLPNTTATAILCSDETIWLEPEVLFAGPRQ
AFEFPQINYQKYSGKPYTYAYGLGLNHFVPDR
LCKLNVKTKETWVWQEADSYPSEPIFVSHPEAMDEDD
gVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS*

>RPE65r_monDom4
MSHQ
VEHPAGGYKKLFETVEELSSPLPAHVR
GRIPPWLAGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKDGRVTYHRR
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISINGMTAHPHIENDGTVYNIGNCFGKNFAIAYNIVKIPPLQA
dKEDPMNKSEVVVQFPCSDRLKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWTLWGANYMDCFESNETMG
VWLHVADKKRGKYLNNKYRTSSFNLFHHINTYEEDNFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAKKAPQPEVRRYVLPLAINK
ADTGKNLVSLPNTTAAAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYAFAYGLGLNHFVPDR
LCKLNVVTKETWLWHEPDSYPSEPIFVSHPDAQEEDD
GVVLSVVVSPGAGQKPACLLVLNAKDMTEVARAEVETNIPVTFHGLFRRS*

>RPE65r_ornAna
MSNQ
VEHPAGGYKKLFETVEELSSPLTAHVT
GRIPVWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRK
FIRTDAYVRAMTEKRIVLTEFGTCAFPDPCKNIFSR
FFSYFRGVEVTDNALVNIYPVGEDYYACTETNFITKINPETLETIKQ
VDLCNYISINGMTAHPHIENDGTVYNIGNCFGKNFAIAYNIVKIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPIKINLFKFLSSWSLWGANYMDCFESNETMG
VWLHVADKNQGRCLNHKYRTSSFNLFHHINTYEDNGFLIVDLCCWKG
FEFVYNYLYLANLRENWEEVKRNAKKAPQPEVRRYVLPLNITK
ADTGKNLVSLPYTTATAILCSDETIWLEPEVLFSGPRQ
AFEFPQINYQKYGGKPYTYTYGLGLNHFVPDR
LCKLNVKTKDTWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSVVVNPGPGQKPAYLLILNAKDMSEVARAEVEINIPVTFHGLFRKS*

>RPE65r_galGal3
MSSQ
VEHPAGGYKKLFETAEELSSPVTAHVT
GRIPTWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
VGRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFSYFKGVEVTDNALVNVYPVGEDYYACTETNFITKINPDTLETIKQ
VDLCKYVSVNGATAHPHVENDGTVYNIGNCFGKNFSLAYNIIRIPPLQA
DKEDPMNKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHVAEKKKGRLLNIKYRTSAFNLFHHINTFEDNGFLIVDLCTWKG
FEFVYNYLYLANLRANWDEVKKQAEKAPQPEARRYVLPLRIDK
ADTGKNLVTLPYTTATATLRSDETVWLEPEVIFSGPRH
AFEFPQINYKKYGGKPYTYTYGLGLNHFVPDR
lCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDD
GVVLSIVISPGSGPKPAYLLILNAKDMSEVARAEVEVNIPVTFHGLFKRA*

>RPE65r_taeGut
MSSQ
VEHPAGGYKKLFETAEELSSPVTAHVT
GRIPTWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRR
FVRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSR
FFTYFKGVEVTDNALVNVYPVGEDYYACTETNFITRINPDTLETIKQ
VDLSKYVSVNGATAHPHIENDGTVYNIGNCFGKNFSLAYNIIRIPPLQA
DKEDPINKSEVVVQFPCSDRFKPSYVHS
FGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMG
VWLHVAEKKKGRLLNLKFRTSAFNLFHHINTYEDNGFLIVDLCTWKG
FEFVYNYLYLANLRANWDEVKRQAEKAPQPEARRYVLPLSIDK
ADTGKNLVTLPYTTATATLRSDETIWLEPEVIFSGPRH
AFEFPQINYTKYGGKPYTYTYGLGLNHFVPDR
lCKLNVKTKETWVWQEPDAYPSEPIFVSHPDALEEDD
GVVLSIVISPGSGPKPAYLLILNAKDMSEVARAEVEVNIPVTFHGLFKRA*

>RPE65r_anoCar
MSSQ
VEHPAGGYKKLFETVEELATPITTHVT
GRIPVWLRGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFEIKEGHVTYYRR
FIRTDCYVRAITEKRIVITEFGTYAYPDPCKNIFSR
FFTYFQGVEVTDNALVNVYPVGEDFYACTETNFLTKINPDNLETLKK
VDISKIVSVNGVTAHPHIENDGTVYNIGNCFGKNFSIAYNIVRIPPLQA
DRKDPMTKCEVVVQFPCSDRFKPSYVHS
FGLTPNYLVFVETPVKINLLKFLSSWSLWGANYMDCFESNESMG
VWMHVADKKKGKYLNIKYRTSPFNLFHHINTYEENGFLIVDLCTWKG
YEFIYNYLYLANLRDNWEEVKKHAQKAPQPEVRRYVLPLNIEK
ADTGKNLITLPNTTATATLNSDETIWLEPEVIFSGPRQ
AFEFPQINYTKYSGKPYTFAYGLGLNHFVPDR
lCKINIKTRETWVWQEPDAYPSEPIFVSHPDALEEDD
GVVLSIIVSPGNGPKPAYLLILSAKDMSEVARAEVDINIPVTFHGFFKKA*

>RPE65r_xenTro
MTNH
VEHPAGGYKKLFETAEELATPMATHVT
GRVPPWLSGSLLRCGPGLFEVGSEQFYHLFDGQALLHKFEIREGHVSYHRR
FVRTDAYVRAMTEKRIVITEFGTFAYPDPCRNIFSR
FFSYFKGLEVTDNALVNVYPVGEDYYACTETNYITKVNPETLETVKK
VDLCNYISINGVTAHPHIESDGTVYNIGNCFGKNFAIAYNVVKTPPLQA
DKEDPITKSTVVVQFPCSDRFKPSYVHS
FGMTPNYLVFVEQPVKINLLKFLSAWSIWGANYMDCFESHETMG
VWMHVAEKHTGEYLNIKYRTSAFNIFHHINTYEDNGFLILDVCCWKG
FEFIYNYLYLANLRENWEEVKKHAEKAPQPEARRYVLPLDINK
NDVGKNLVSLNYTTATATLHSDGTIWLEPEVLFSGPRQ
AFEFPQINYKKYGGKDYSYAYGLGLNHFIPDR
lTKLNVKTKETWVWQEPNAYPSEPIFVQAPDAIEEDD
GIVLSAVISPAVGHKPSYLLILDAKDMSEIARAEVDTIIPVTFHGMFKRA*

>RPE65r_tetNig
----
VEHPAGGYKKIFETVEELDEPVAAKIS
GTLPAWLSGSLLRMGPGLFEVGDEPFRHLFDGQALIHKFDLKEGHVTYHRK
FIRTDAYVRAMTENRVVITELGTAAYPDPCKNIFSR
FFTYFKGVEVTDNCMVNIYTIGEDFYAVTETNFITKVDPDSLETLKK
VDLSKYLSVNGVTAHPHKDADGTVYNIGNCFGKNMSLAYNIVKIPPAQK
DSLEPFEKARVVVQLPSSERLKPSYIHS
FGMSDNYFVFVEPPVKINLIKFLSAWSIRGATYMDCFESNETLG
TWFHLATKDPADYSSYKFRTSAFNIFHHINTYEDQGFMVVDLCTWKG
HEFVYNYLYVANLRQEWEEVKKAAMKAPQPEVRRYVLPLDISS
EDLGKNLVSLSYTTATAVLRRDGTIWLEPEVLFSGPRL
AFEFPQINYSEYSGKMYHFTYGLGLNHFIPDR
LMKLNVQTKETQEWREEECYPSEPLFVPTPGATDEDD
GVLLSVVVKPGA--RPGFLLVLDAKTLSELGRAEVSVNIPVTLHGMFKLT*

>RPE65r_fr
----
VEHPAAGYKKIFETVEELNEPIAATIS
GVIPTWLSGSLLRMGPGLFEVGDQPLHHLFDGQALIHKFDLKDGRVTYYRK
FIRTDAYVRAMTENRVVITEFGTAAYPDPCKNIFSR
FFTYFKGIEVTDNCLVNIYTIGEDFYAVTETNFITKVDPDSLETLKK
VDLSKYVSVNGITAHPHKDPDGTVYNIGNCFGKNMSLAYNIVKIPPAPK
DSLEPFEKARVVVQLPSSERLKPSYIHS
FGMTENYFVFVEPPVKINLLKFLSAWSVRGATYMDCFESNETLG
TWFHLATKDPADYSSYKFRTSAFNVFHHINTYKDQDFIVVDLCTWKG
FEFVYNYLWLANLRANWDEVKKAAMMAPQPEVRRYVIPLDVHK
EDMGKNLVSLSYTTATAVLRSDGTIWLEPEVLFSGPRH
AFEFPQINYSEYSGKMYRFAFGLGLNHFIPDR
lMKLNVQTKEMREWREEECYPSEPLFVATPGATDEDD
GVLLSVVVKPGA--RPGSLLVLDAKTLTEVGRAEVSVNIPVTLHGMFKLT*

>RPE65r_gasAcu
----
VEHPAAGYKKIFETVEELNEPIPARVI
GVLPSWLGGSLLRMGPGLFEVGGEPFNHLFDGQALIHKFDLKNGQVTYYRK
FIRTDTYVRAMTENRVVITEFGTAAYPDPCKNIFSR
FFTYFKGIEVTDNCLVNICPIGEDFYAVTETNYITKVDPDSLETLKK
vDLCKYVSVNGVTAHPHTDADGTVYNIGNCFGKNFSLAYNIVKIPPPQE
DKSDPLERAQVVLQLPSSERLKPSYLHS
FGMTDNHFVFVEQPVKINVLKYLSAWSVRGTTYMDCFESNDSMG
TWFHLATKDPADYSSYKFRTSAFNIFHHINAYEDQGFIVVDLCTWKG
HDFVYDYLYLANLKGEWEEVKKAAMRAPQPEVRRYVLPLDIHR
EEQGRNLVSLSYTTATAALRSDGTIWLEPEVLFSGPRQ
AFEFPQINYSLCRGKKYSFAYGLGLNHFIPDR
VVKLNVQTKETWVWQEDECYPSEPLFVPTPAATEEDD
GVLLSIVVKPGA--RPSFLLVLDAVKLTELARAEVNTIIPVTLHGTYKlt*

>RPE65r_oryLat
----
VEHPAAGYKKIFETVEELDEPIPAQIS
GVIPSWLGGSLLRMGPGLFEVGDEPFHHLFDGQALMHKFDLRNGQVTYNRK
FIKTDSYVRAMTENRVVITEFGTIAYPDPCKNIFSR
FFSYFKGIEVTDNCLVNIYPIGEDFYAVTETNYITKVDPDSLETLEK
VDVCKYLSVNGLTAHPHIEADGTVYNIGNCFGKDMSLAYNIVKIPPAQK
DKSDPIEKSQIVVQLPSSERLKPSYVHS
FGMTNNYFVFVEQPVKINLLKFLSAWSIRGTTYMDCFESCESMG
TWFHLTTKNPAAYSSHKFRTSAFNLFHHINTYEDQGFIVVDLCTWKG
HEFVYNYLYLANLREEWEEVKKAASRAPQPEVRRYVLPLDIYK
EEQGKNLVSLSYTTATAVLCSDGTIWLEPEVLFSGPRQ
AFEFPQINYSQCCGKKYFFAYGLGLNHFIPDR
VVKLNVQTKETWVWQEEDCYPSEPIFVATPGATQEDD
GVLLSIVVKPGT--RPGFLLVLDAMKLTEVARAEVNAIIPVTLHGLYKMT*

>RPE65r_danRer5
----
LEHPAGGYKKVFESCEELAEPIPAHVS
GEIPAWLSGSLLRMGPGLFEVGDEPFYHLFDGQALLHKFDLKDGRVTYHRR
FIRTDAYVRAMTEKRVVITEFGTTAYPDPCKNIFSR
FFTYFQGIEVTDNCLVNIYPIGEDFYACTETNFITKVDPDTLETVKK
VDLCNYLSVNGLTAHPHIEADGTVYNIGNCFGKNMSLAYNIVKIPPLQE
DKSDQFEKSKILVQFPSSERFKPSYVHS
FGITENHFVFVETPVKINLLKFLTSWSIRGSNYMDCFESNDKMG
TWFHLAAKNPGKYIDHKFRTSAFNIFHHINCFEDQGFIVVDLCTWKG
HEFVYNYLYLANLRQNWEEVKKAALRAPQPEVRRYVLPLDIHR
EEQGKNLVSLPYTTATAVMRSDGTVWLEPEVLFSGPRQ
AFEFPQINYSKFNGKDYTFAYGLGLNHFVPDR
FCKLNVKSKETWIWQEPDAYPSEPLFVQSPDAEDEDD
GVLLSIVVKPGA--RPAFLLILKATDLTEIARAEVDVLIPLTLHGIYTLt*