ID TYRP1_HUMAN Reviewed; 537 AA. AC P17643; P78468; P78469; Q13721; Q15679; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 2. DT 24-JAN-2024, entry version 214. DE RecName: Full=5,6-dihydroxyindole-2-carboxylic acid oxidase; DE Short=DHICA oxidase; DE EC=1.14.18.- {ECO:0000269|PubMed:28661582}; DE AltName: Full=Catalase B; DE AltName: Full=Glycoprotein 75 {ECO:0000303|PubMed:1693779}; DE AltName: Full=Melanoma antigen gp75 {ECO:0000303|PubMed:2324688}; DE AltName: Full=Tyrosinase-related protein 1 {ECO:0000303|PubMed:9434945}; DE Short=TRP {ECO:0000303|PubMed:2111010}; DE Short=TRP-1; DE Short=TRP1; DE Flags: Precursor; GN Name=TYRP1 {ECO:0000312|HGNC:HGNC:12450}; GN Synonyms=CAS2 {ECO:0000303|PubMed:1906272}, TYRP, TYRRP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Melanoma; RX PubMed=2111010; DOI=10.1093/nar/18.9.2807; RA Cohen T., Muller R.M., Tomita Y., Shibahara S.; RT "Nucleotide sequence of the cDNA encoding human tyrosinase-related RT protein."; RL Nucleic Acids Res. 18:2807-2807(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1906272; DOI=10.1016/0006-291x(91)91803-k; RA Chintamaneni C.D., Ramsay M., Colman M.-A., Fox M.F., Pickard R.T., RA Kwon B.S.; RT "Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, RT to human chromosome 9p22-pter."; RL Biochem. Biophys. Res. Commun. 178:227-235(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9434945; DOI=10.1007/s003359900678; RA Box N.F., Wyeth J.R., Mayne C.J., O'Gorman L.E., Martin N.G., Sturm R.A.; RT "Complete sequence and polymorphism study of the human TYRP1 gene encoding RT tyrosinase-related protein 1."; RL Mamm. Genome 9:50-53(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-128. RC TISSUE=Liver; RX PubMed=8530077; DOI=10.1006/geno.1995.1211; RA Sturm R.A., O'Sullivan B.J., Box N.F., Smith A.G., Smit S.E., RA Puttick E.R.J., Parsons P.G., Dunn I.S.; RT "Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of RT the tyrosinase-related protein gene family."; RL Genomics 29:24-34(1995). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17. RX PubMed=1575733; DOI=10.1016/0006-291x(92)90627-w; RA Shibata K., Takeda K., Tomita Y., Tagami H., Shibahara S.; RT "Downstream region of the human tyrosinase-related protein gene enhances RT its promoter activity."; RL Biochem. Biophys. Res. Commun. 184:568-575(1992). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 218-465, AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Melanoma; RX PubMed=2324688; DOI=10.1084/jem.171.4.1375; RA Vijayasaradhi S., Bouchard B., Houghton A.N.; RT "The melanoma antigen gp75 is the human homologue of the mouse b (brown) RT locus gene product."; RL J. Exp. Med. 171:1375-1380(1990). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 481-537. RC TISSUE=Blood, and Hair root; RX PubMed=1945866; DOI=10.1093/nar/19.20.5803; RA Urquhart A.J.; RT "Human tyrosinase-like protein (TYRL) carboxy terminus: closer homology RT with the mouse protein than previously reported."; RL Nucleic Acids Res. 19:5803-5803(1991). RN [9] RP POSSIBLE FUNCTION. RX PubMed=1693779; DOI=10.1073/pnas.87.12.4809; RA Halaban R., Moellmann G.; RT "Murine and human b locus pigmentation genes encode a glycoprotein (gp75) RT with catalase activity."; RL Proc. Natl. Acad. Sci. U.S.A. 87:4809-4813(1990). RN [10] RP LACK OF DHICA OXIDASE ACTIVITY. RX PubMed=9758418; DOI=10.1111/j.1600-0625.1998.tb00324.x; RA Boissy R.E., Sakai C., Zhao H., Kobayashi T., Hearing V.J.; RT "Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA RT oxidase activity in contrast to murine TRP-1."; RL Exp. Dermatol. 7:198-204(1998). RN [11] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [12] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [13] {ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 25-470 IN COMPLEX WITH ZINC IONS RP AND SYNTHETIC INHIBITORS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, GLYCOSYLATION AT ASN-96; ASN-104; ASN-181; ASN-304; ASN-350 AND RP ASN-385, DISULFIDE BONDS, AND MUTAGENESIS OF TYR-362; ARG-374 AND THR-391. RX PubMed=28661582; DOI=10.1002/anie.201704616; RA Lai X., Wichers H.J., Soler-Lopez M., Dijkstra B.W.; RT "Structure of Human Tyrosinase Related Protein1 Reveals a Binuclear Zinc RT Active Site Important for Melanogenesis."; RL Angew. Chem. Int. Ed. Engl. 56:9812-9815(2017). RN [14] RP INVOLVEMENT IN SHEP11, VARIANT CYS-93, ASSOCIATION OF VARIANT CYS-93 WITH RP BLOND HAIR, FUNCTION, AND PATHWAY. RX PubMed=22556244; DOI=10.1126/science.1217849; RA Kenny E.E., Timpson N.J., Sikora M., Yee M.C., Moreno-Estrada A., Eng C., RA Huntsman S., Burchard E.G., Stoneking M., Bustamante C.D., Myles S.; RT "Melanesian blond hair is caused by an amino acid change in TYRP1."; RL Science 336:554-554(2012). RN [15] RP VARIANT OCA3 GLN-356, PATHWAY, AND FUNCTION. RX PubMed=16704458; DOI=10.1111/j.1600-0749.2006.00298.x; RA Rooryck C., Roudaut C., Robine E., Muesebeck J., Arveiler B.; RT "Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian RT patient."; RL Pigment Cell Res. 19:239-242(2006). RN [16] RP VARIANT OCA3 THR-24, PATHWAY, AND FUNCTION. RX PubMed=23504663; DOI=10.1002/humu.22315; RA Simeonov D.R., Wang X., Wang C., Sergeev Y., Dolinska M., Bower M., RA Fischer R., Winer D., Dubrovsky G., Balog J.Z., Huizing M., Hart R., RA Zein W.M., Gahl W.A., Brooks B.P., Adams D.R.; RT "DNA variations in oculocutaneous albinism: an updated mutation list and RT current outstanding issues in molecular diagnostics."; RL Hum. Mutat. 34:827-835(2013). CC -!- FUNCTION: Plays a role in melanin biosynthesis (PubMed:22556244, CC PubMed:16704458, PubMed:23504663). Catalyzes the oxidation of 5,6- CC dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2- CC carboxylic acid in the presence of bound Cu(2+) ions, but not in the CC presence of Zn(2+) (PubMed:28661582). May regulate or influence the CC type of melanin synthesized (PubMed:22556244, PubMed:16704458). Also to CC a lower extent, capable of hydroxylating tyrosine and producing melanin CC (By similarity). {ECO:0000250|UniProtKB:P07147, CC ECO:0000269|PubMed:16704458, ECO:0000269|PubMed:22556244, CC ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:28661582}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 H2O + 2 CC indole-5,6-quinone-2-carboxylate; Xref=Rhea:RHEA:68388, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16875, CC ChEBI:CHEBI:177869; Evidence={ECO:0000269|PubMed:28661582}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68389; CC Evidence={ECO:0000305|PubMed:28661582}; CC -!- COFACTOR: CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036; CC Evidence={ECO:0000269|PubMed:28661582}; CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:28661582}; CC Note=Contains bound zinc ions after heterologous expression in insect CC cells, giving rise to a protein that lacks DHICA oxidase activity. CC {ECO:0000269|PubMed:28661582}; CC -!- ACTIVITY REGULATION: The activity depends critically on the nature of CC the bound metal ion. Catalyzes the oxidation of 5,6-dihydroxyindole-2- CC carboxylic acid (DHICA) in the presence of bound Cu(2+) ions, but lacks CC activity in the presence of bound Zn(2+) ions. CC {ECO:0000269|PubMed:28661582}. CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis. CC {ECO:0000269|PubMed:16704458, ECO:0000269|PubMed:22556244, CC ECO:0000269|PubMed:23504663}. CC -!- SUBUNIT: Monomer (PubMed:28661582). Interacts with ATP7A (By CC similarity) (PubMed:28661582). Interacts with SLC45A2 (By similarity). CC {ECO:0000250|UniProtKB:P07147, ECO:0000269|PubMed:28661582}. CC -!- INTERACTION: CC P17643; O14908: GIPC1; NbExp=3; IntAct=EBI-7900408, EBI-373132; CC P17643; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-7900408, EBI-8652744; CC -!- SUBCELLULAR LOCATION: Melanosome membrane CC {ECO:0000250|UniProtKB:P07147}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P07147}. Note=Located to mature stage III and IV CC melanosomes and apposed endosomal tubular membranes. Transported to CC pigmented melanosomes by the BLOC-1 complex. Proper trafficking to CC melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38. CC {ECO:0000250|UniProtKB:P07147}. CC -!- TISSUE SPECIFICITY: Pigment cells. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P07147}. CC -!- POLYMORPHISM: Genetic variants in TYRP1 define the skin/hair/eye CC pigmentation variation locus 11 (SHEP11) [MIM:612271] and are CC responsible for variability in hair color linked to chromosome 9p23 in CC Melanesians. Hair, eye and skin pigmentation are among the most visible CC examples of human phenotypic variation, with a broad normal range that CC is subject to substantial geographic stratification. CC {ECO:0000269|PubMed:22556244}. CC -!- DISEASE: Albinism, oculocutaneous, 3 (OCA3) [MIM:203290]: An autosomal CC recessive disorder in which the biosynthesis of melanin pigment is CC reduced in skin, hair, and eyes. Tyrosinase activity is normal and CC patients have only moderate reduction of pigment. The eyes present red CC reflex on transillumination of the iris, dilution of color of iris, CC nystagmus and strabismus. Darker-skinned individuals have bright CC copper-red coloration of the skin and hair. CC {ECO:0000269|PubMed:16704458, ECO:0000269|PubMed:23504663}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}. CC -!- CAUTION: The precise function of this protein in melanin biosynthesis CC is still under debate. DHICA oxidase activity is controversial CC (PubMed:9758418, PubMed:28661582). Lacks DHICA oxidase activity CC (PubMed:9758418). Has DHICA oxidase activity in the presence of Cu(2+), CC but lacks DHICA oxidase activity with Zn(2+) (PubMed:28661582). CC {ECO:0000269|PubMed:28661582, ECO:0000269|PubMed:9758418}. CC -!- WEB RESOURCE: Name=Mutations of the TYRP1 gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/trp1mut.htm"; CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=TYRP1 mutations; CC URL="http://www.ifpcs.org/albinism/oca3mut.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X51420; CAA35785.1; -; mRNA. DR EMBL; AF001295; AAC15468.1; -; Genomic_DNA. DR EMBL; L38952; AAC41924.1; -; Genomic_DNA. DR EMBL; D83059; BAA11759.1; -; Genomic_DNA. DR EMBL; BC052608; AAH52608.1; -; mRNA. DR EMBL; X51455; CAA35820.1; -; mRNA. DR EMBL; X60955; CAA43288.1; -; Genomic_DNA. DR CCDS; CCDS34990.1; -. DR PIR; S09999; YRHUB6. DR RefSeq; NP_000541.1; NM_000550.2. DR PDB; 5M8L; X-ray; 2.35 A; A/B/C/D=25-470. DR PDB; 5M8M; X-ray; 2.65 A; A/B/C/D=25-470. DR PDB; 5M8N; X-ray; 2.60 A; A/B/C/D=25-470. DR PDB; 5M8O; X-ray; 2.50 A; A/B/C/D=25-470. DR PDB; 5M8P; X-ray; 2.80 A; A/B/C/D=25-470. DR PDB; 5M8Q; X-ray; 2.85 A; A/B/C/D=25-470. DR PDB; 5M8R; X-ray; 2.40 A; A/B/C/D=25-470. DR PDB; 5M8S; X-ray; 2.20 A; A/B/C/D=25-470. DR PDB; 5M8T; X-ray; 2.35 A; A/B/C/D=25-470. DR PDBsum; 5M8L; -. DR PDBsum; 5M8M; -. DR PDBsum; 5M8N; -. DR PDBsum; 5M8O; -. DR PDBsum; 5M8P; -. DR PDBsum; 5M8Q; -. DR PDBsum; 5M8R; -. DR PDBsum; 5M8S; -. DR PDBsum; 5M8T; -. DR AlphaFoldDB; P17643; -. DR SMR; P17643; -. DR BioGRID; 113156; 9. DR IntAct; P17643; 3. DR MINT; P17643; -. DR STRING; 9606.ENSP00000373570; -. DR ChEMBL; CHEMBL3712886; -. DR TCDB; 9.B.423.1.2; the tysrosinase (tyr) family. DR GlyCosmos; P17643; 6 sites, No reported glycans. DR GlyGen; P17643; 6 sites. DR iPTMnet; P17643; -. DR PhosphoSitePlus; P17643; -. DR BioMuta; TYRP1; -. DR DMDM; 12644141; -. DR MassIVE; P17643; -. DR PaxDb; 9606-ENSP00000373570; -. DR PeptideAtlas; P17643; -. DR ProteomicsDB; 53498; -. DR ABCD; P17643; 3 sequenced antibodies. DR Antibodypedia; 745; 872 antibodies from 32 providers. DR DNASU; 7306; -. DR Ensembl; ENST00000388918.10; ENSP00000373570.4; ENSG00000107165.13. DR GeneID; 7306; -. DR KEGG; hsa:7306; -. DR MANE-Select; ENST00000388918.10; ENSP00000373570.4; NM_000550.3; NP_000541.1. DR UCSC; uc003zkv.5; human. DR AGR; HGNC:12450; -. DR CTD; 7306; -. DR DisGeNET; 7306; -. DR GeneCards; TYRP1; -. DR HGNC; HGNC:12450; TYRP1. DR HPA; ENSG00000107165; Group enriched (choroid plexus, heart muscle, skin). DR MalaCards; TYRP1; -. DR MIM; 115501; gene. DR MIM; 203290; phenotype. DR MIM; 612271; phenotype. DR neXtProt; NX_P17643; -. DR OpenTargets; ENSG00000107165; -. DR Orphanet; 79433; Oculocutaneous albinism type 3. DR PharmGKB; PA37101; -. DR VEuPathDB; HostDB:ENSG00000107165; -. DR eggNOG; ENOG502QRNA; Eukaryota. DR GeneTree; ENSGT00940000155804; -. DR HOGENOM; CLU_038693_1_0_1; -. DR InParanoid; P17643; -. DR OMA; RNTCDIC; -. DR OrthoDB; 70287at2759; -. DR PhylomeDB; P17643; -. DR TreeFam; TF315865; -. DR PathwayCommons; P17643; -. DR Reactome; R-HSA-5662702; Melanin biosynthesis. DR SignaLink; P17643; -. DR SIGNOR; P17643; -. DR UniPathway; UPA00785; -. DR BioGRID-ORCS; 7306; 9 hits in 1151 CRISPR screens. DR ChiTaRS; TYRP1; human. DR GeneWiki; TYRP1; -. DR GenomeRNAi; 7306; -. DR Pharos; P17643; Tbio. DR PRO; PR:P17643; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P17643; Protein. DR Bgee; ENSG00000107165; Expressed in pigmented layer of retina and 138 other cell types or tissues. DR ExpressionAtlas; P17643; baseline and differential. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0097708; C:intracellular vesicle; IDA:UniProtKB. DR GO; GO:0042470; C:melanosome; ISS:UniProtKB. DR GO; GO:0033162; C:melanosome membrane; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0016491; F:oxidoreductase activity; TAS:Reactome. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0004503; F:tyrosinase activity; IDA:UniProtKB. DR GO; GO:0043438; P:acetoacetic acid metabolic process; IEA:Ensembl. DR GO; GO:0042438; P:melanin biosynthetic process; TAS:Reactome. DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central. DR GO; GO:0032438; P:melanosome organization; IBA:GO_Central. DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IMP:CACAO. DR Gene3D; 1.10.1280.10; Di-copper center containing domain from catechol oxidase; 1. DR InterPro; IPR008922; Di-copper_centre_dom_sf. DR InterPro; IPR002227; Tyrosinase_Cu-bd. DR PANTHER; PTHR11474:SF3; 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID OXIDASE; 1. DR PANTHER; PTHR11474; TYROSINASE FAMILY MEMBER; 1. DR Pfam; PF00264; Tyrosinase; 1. DR PRINTS; PR00092; TYROSINASE. DR SUPFAM; SSF48056; Di-copper centre-containing domain; 1. DR PROSITE; PS00497; TYROSINASE_1; 1. DR PROSITE; PS00498; TYROSINASE_2; 1. DR Genevisible; P17643; HS. PE 1: Evidence at protein level; KW 3D-structure; Albinism; Copper; Direct protein sequencing; Disease variant; KW Disulfide bond; Glycoprotein; Melanin biosynthesis; Membrane; KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..24 FT CHAIN 25..537 FT /note="5,6-dihydroxyindole-2-carboxylic acid oxidase" FT /id="PRO_0000035889" FT TOPO_DOM 25..477 FT /note="Lumenal, melanosome" FT /evidence="ECO:0000255" FT TRANSMEM 478..501 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 502..537 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT BINDING 192 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="A" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="A" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT BINDING 224 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="A" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT BINDING 377 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="B" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT BINDING 381 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="B" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT BINDING 404 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="B" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 96 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 104 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 181 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 304 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 350 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT CARBOHYD 385 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L" FT DISULFID 30..41 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 42..65 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 56..99 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 101..110 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 113..122 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 258..261 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT DISULFID 290..303 FT /evidence="ECO:0000269|PubMed:28661582, FT ECO:0007744|PDB:5M8L, ECO:0007744|PDB:5M8M, FT ECO:0007744|PDB:5M8N, ECO:0007744|PDB:5M8O, FT ECO:0007744|PDB:5M8P, ECO:0007744|PDB:5M8Q, FT ECO:0007744|PDB:5M8R, ECO:0007744|PDB:5M8T" FT VARIANT 24 FT /note="A -> T (in OCA3; dbSNP:rs61758405)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072599" FT VARIANT 93 FT /note="R -> C (associated with blond hair in individuals FT from the Solomon Islands; rare or absent outside of FT Oceania; dbSNP:rs387907171)" FT /evidence="ECO:0000269|PubMed:22556244" FT /id="VAR_068176" FT VARIANT 326 FT /note="R -> H (in dbSNP:rs16929374)" FT /id="VAR_026827" FT VARIANT 356 FT /note="R -> Q (in OCA3; dbSNP:rs281865424)" FT /evidence="ECO:0000269|PubMed:16704458" FT /id="VAR_026828" FT MUTAGEN 362 FT /note="Y->F: No effect; when associated with S-374 and FT V-391." FT /evidence="ECO:0000269|PubMed:28661582" FT MUTAGEN 374 FT /note="R->S: No effect; when associated with F-362 and FT V-391." FT /evidence="ECO:0000269|PubMed:28661582" FT MUTAGEN 391 FT /note="T->V: No effect; when associated with F-362 and FT S-374." FT /evidence="ECO:0000269|PubMed:28661582" FT CONFLICT 395..396 FT /note="PN -> SQ (in Ref. 7; CAA35820)" FT /evidence="ECO:0000305" FT CONFLICT 526..537 FT /note="YEKLQNPNQSVV -> RI (in Ref. 1; CAA35785 and 2)" FT /evidence="ECO:0000305" FT TURN 28..30 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 33..38 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 44..46 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 56..61 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 62..67 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 86..94 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 96..101 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 119..122 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 138..153 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 157..164 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 179..183 FT /evidence="ECO:0007829|PDB:5M8Q" FT HELIX 184..196 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 203..205 FT /evidence="ECO:0007829|PDB:5M8Q" FT STRAND 213..217 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 220..239 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 263..266 FT /evidence="ECO:0007829|PDB:5M8L" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:5M8N" FT HELIX 282..285 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 293..299 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 330..336 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 355..360 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 376..383 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 391..393 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 394..396 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 399..417 FT /evidence="ECO:0007829|PDB:5M8S" FT TURN 418..420 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:5M8L" FT STRAND 427..431 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 449..452 FT /evidence="ECO:0007829|PDB:5M8S" FT HELIX 456..459 FT /evidence="ECO:0007829|PDB:5M8S" FT STRAND 461..464 FT /evidence="ECO:0007829|PDB:5M8S" SQ SEQUENCE 537 AA; 60724 MW; 1051CEEF52908CCA CRC64; MSAPKLLSLG CIFFPLLLFQ QARAQFPRQC ATVEALRSGM CCPDLSPVSG PGTDRCGSSS GRGRCEAVTA DSRPHSPQYP HDGRDDREVW PLRFFNRTCH CNGNFSGHNC GTCRPGWRGA ACDQRVLIVR RNLLDLSKEE KNHFVRALDM AKRTTHPLFV IATRRSEEIL GPDGNTPQFE NISIYNYFVW THYYSVKKTF LGVGQESFGE VDFSHEGPAF LTWHRYHLLR LEKDMQEMLQ EPSFSLPYWN FATGKNVCDI CTDDLMGSRS NFDSTLISPN SVFSQWRVVC DSLEDYDTLG TLCNSTEDGP IRRNPAGNVA RPMVQRLPEP QDVAQCLEVG LFDTPPFYSN STNSFRNTVE GYSDPTGKYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA DISTFPLENA PIGHNRQYNM VPFWPPVTNT EMFVTAPDNL GYTYEIQWPS REFSVPEIIA IAVVGALLLV ALIFGTASYL IRARRSMDEA NQPLLTDQYQ CYAEEYEKLQ NPNQSVV //