TYRP1_HUMAN
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 03-AUG-2022, entry version 206.
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; 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). Catalyzes the oxidation of 5,6-dihydroxyindole-2-
CC carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in
CC the presence of bound Cu(2+) ions, but not in the presence of Zn(2+)
CC (PubMed:28661582). May regulate or influence the type of melanin
CC synthesized (PubMed:22556244, PubMed:16704458). Also to a lower extent,
CC capable of hydroxylating tyrosine and producing melanin (By
CC similarity). {ECO:0000250|UniProtKB:P07147,
CC ECO:0000269|PubMed:16704458, ECO:0000269|PubMed:22556244,
CC ECO:0000269|PubMed:28661582, ECO:0000305|PubMed:16704458,
CC ECO:0000305|PubMed:22556244, ECO:0000305|PubMed:23504663}.
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). {ECO:0000250|UniProtKB:P07147,
CC 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}. Melanosome
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";
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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 GlyGen; P17643; 6 sites.
DR iPTMnet; P17643; -.
DR PhosphoSitePlus; P17643; -.
DR BioMuta; TYRP1; -.
DR DMDM; 12644141; -.
DR MassIVE; P17643; -.
DR PaxDb; P17643; -.
DR PeptideAtlas; P17643; -.
DR PRIDE; P17643; -.
DR ProteomicsDB; 53498; -.
DR ABCD; P17643; 3 sequenced antibodies.
DR Antibodypedia; 745; 742 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 CTD; 7306; -.
DR DisGeNET; 7306; -.
DR GeneCards; TYRP1; -.
DR HGNC; HGNC:12450; TYRP1.
DR HPA; ENSG00000107165; Tissue enhanced (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; AGATCIV; -.
DR OrthoDB; 518234at2759; -.
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 1067 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 137 other tissues.
DR ExpressionAtlas; P17643; baseline and differential.
DR Genevisible; P17643; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 1.
DR InterPro; IPR008922; Di-copper_centre_dom_sf.
DR InterPro; IPR002227; Tyrosinase_Cu-bd.
DR Pfam; PF00264; Tyrosinase; 1.
DR PRINTS; PR00092; TYROSINASE.
DR SUPFAM; SSF48056; SSF48056; 1.
DR PROSITE; PS00497; TYROSINASE_1; 1.
DR PROSITE; PS00498; TYROSINASE_2; 1.
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 V-
FT 391."
FT /evidence="ECO:0000269|PubMed:28661582"
FT MUTAGEN 374
FT /note="R->S: No effect; when associated with F-362 and V-
FT 391."
FT /evidence="ECO:0000269|PubMed:28661582"
FT MUTAGEN 391
FT /note="T->V: No effect; when associated with F-362 and S-
FT 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
