TYRP2_HUMAN
ID TYRP2_HUMAN Reviewed; 519 AA.
AC P40126; Q09GT4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=L-dopachrome tautomerase {ECO:0000305};
DE Short=DCT;
DE Short=DT;
DE EC=5.3.3.12 {ECO:0000250|UniProtKB:P29812};
DE AltName: Full=L-dopachrome Delta-isomerase;
DE AltName: Full=Tyrosinase-related protein 2;
DE Short=TRP-2;
DE Short=TRP2;
DE Flags: Precursor;
GN Name=DCT {ECO:0000312|HGNC:HGNC:2709}; Synonyms=TYRP2;
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] (ISOFORM 1).
RX PubMed=8148378; DOI=10.1016/0167-4781(94)90292-5;
RA Yokoyama K., Suzuki H., Yasumoto K.I., Tomita Y., Shibahara S.;
RT "Molecular cloning and functional analysis of a cDNA coding for human
RT DOPAchrome tautomerase/tyrosinase-related protein-2.";
RL Biochim. Biophys. Acta 1217:317-321(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8206391; DOI=10.1016/0378-1119(94)90114-7;
RA Cassady J.L., Sturm R.A.;
RT "Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA.";
RL Gene 143:295-298(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=8306979; DOI=10.1111/j.1432-1033.1994.tb19922.x;
RA Bouchard B., del Marmol V., Jackson I.J., Cherif D., Dubertret L.;
RT "Molecular characterization of a human tyrosinase-related-protein-2 cDNA.
RT Patterns of expression in melanocytic cells.";
RL Eur. J. Biochem. 219:127-134(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Melanoma;
RX PubMed=11777994; DOI=10.4049/jimmunol.168.2.951;
RA Khong H.T., Rosenberg S.A.;
RT "Pre-existing immunity to tyrosinase-related protein (TRP)-2, a new TRP-2
RT isoform, and the NY-ESO-1 melanoma antigen in a patient with a dramatic
RT response to immunotherapy.";
RL J. Immunol. 168:951-956(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98.
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98.
RC TISSUE=Liver;
RX PubMed=7929451; DOI=10.1016/s0021-9258(18)47128-1;
RA Yokoyama K., Yasumoto K.I., Suzuki H., Shibahara S.;
RT "Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2
RT gene and identification of two regulatory regions required for its pigment
RT cell-specific expression.";
RL J. Biol. Chem. 269:27080-27087(1994).
RN [9]
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 [10]
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 [11]
RP INTERACTION WITH TYR, AND INDUCTION BY BLUE LIGHT.
RX PubMed=28842328; DOI=10.1016/j.jid.2017.07.833;
RA Regazzetti C., Sormani L., Debayle D., Bernerd F., Tulic M.K.,
RA De Donatis G.M., Chignon-Sicard B., Rocchi S., Passeron T.;
RT "Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3.";
RL J. Invest. Dermatol. 138:171-178(2018).
RN [12]
RP VARIANTS OCA8 SER-40 AND TRP-61, AND FUNCTION.
RX PubMed=33100333; DOI=10.1038/s41436-020-00997-8;
RA Pennamen P., Tingaud-Sequeira A., Gazova I., Keighren M., McKie L.,
RA Marlin S., Gherbi Halem S., Kaplan J., Delevoye C., Lacombe D.,
RA Plaisant C., Michaud V., Lasseaux E., Javerzat S., Jackson I., Arveiler B.;
RT "Dopachrome tautomerase variants in patients with oculocutaneous
RT albinism.";
RL Genet. Med. 23:479-487(2021).
CC -!- FUNCTION: Plays a role in melanin biosynthesis (PubMed:33100333).
CC Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-
CC carboxylic acid (DHICA). {ECO:0000269|PubMed:33100333,
CC ECO:0000269|PubMed:8306979}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-dopachrome = 5,6-dihydroxyindole-2-carboxylate;
CC Xref=Rhea:RHEA:13041, ChEBI:CHEBI:16875, ChEBI:CHEBI:57509;
CC EC=5.3.3.12; Evidence={ECO:0000250|UniProtKB:P29812};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P29812};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P29812};
CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC {ECO:0000269|PubMed:33100333}.
CC -!- SUBUNIT: Forms an OPN3-dependent complex with TYR in response to blue
CC light in melanocytes. {ECO:0000269|PubMed:28842328}.
CC -!- INTERACTION:
CC P40126; P60201-2: PLP1; NbExp=3; IntAct=EBI-18640065, EBI-12188331;
CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Melanosome
CC {ECO:0000250|UniProtKB:P29812}. Note=Proper trafficking to melanosome
CC is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
CC {ECO:0000250|UniProtKB:P29812}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P40126-1; Sequence=Displayed;
CC Name=2; Synonyms=TRP-2-6b;
CC IsoId=P40126-2; Sequence=VSP_043581;
CC -!- INDUCTION: Induced by blue light (415nm).
CC {ECO:0000269|PubMed:28842328}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P29812}.
CC -!- DISEASE: Albinism, oculocutaneous, 8 (OCA8) [MIM:619165]: A form of
CC oculocutaneous albinism, a disorder of pigmentation characterized by
CC reduced biosynthesis of melanin in the skin, hair and eyes. OCA8 is an
CC autosomal recessive form characterized by mild hair and skin
CC hypopigmentation, associated with ocular features including nystagmus,
CC reduced visual acuity, iris transillumination, and hypopigmentation of
CC the retina. {ECO:0000269|PubMed:33100333}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
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DR EMBL; D17547; BAA04484.1; -; mRNA.
DR EMBL; L18967; AAA20870.1; -; mRNA.
DR EMBL; S69231; AAC60627.1; -; mRNA.
DR EMBL; DQ902581; ABI73976.1; -; mRNA.
DR EMBL; AL139318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028311; AAH28311.1; -; mRNA.
DR EMBL; L38953; AAC41925.1; -; Genomic_DNA.
DR EMBL; D28767; BAA05956.1; -; Genomic_DNA.
DR CCDS; CCDS45060.1; -. [P40126-2]
DR CCDS; CCDS9470.1; -. [P40126-1]
DR PIR; S43510; YRHUR2.
DR RefSeq; NP_001123361.1; NM_001129889.2. [P40126-2]
DR RefSeq; NP_001913.2; NM_001922.4. [P40126-1]
DR PDB; 4HX1; X-ray; 1.80 A; C=180-188.
DR PDBsum; 4HX1; -.
DR AlphaFoldDB; P40126; -.
DR SMR; P40126; -.
DR BioGRID; 108006; 29.
DR IntAct; P40126; 8.
DR STRING; 9606.ENSP00000392762; -.
DR TCDB; 9.B.423.1.3; the tysrosinase (tyr) family.
DR GlyGen; P40126; 6 sites.
DR iPTMnet; P40126; -.
DR PhosphoSitePlus; P40126; -.
DR BioMuta; DCT; -.
DR DMDM; 731026; -.
DR EPD; P40126; -.
DR jPOST; P40126; -.
DR MassIVE; P40126; -.
DR PeptideAtlas; P40126; -.
DR PRIDE; P40126; -.
DR ProteomicsDB; 55335; -. [P40126-1]
DR ProteomicsDB; 55336; -. [P40126-2]
DR Antibodypedia; 2252; 430 antibodies from 33 providers.
DR DNASU; 1638; -.
DR Ensembl; ENST00000377028.10; ENSP00000366227.4; ENSG00000080166.16. [P40126-1]
DR Ensembl; ENST00000446125.1; ENSP00000392762.1; ENSG00000080166.16. [P40126-2]
DR GeneID; 1638; -.
DR KEGG; hsa:1638; -.
DR MANE-Select; ENST00000377028.10; ENSP00000366227.4; NM_001922.5; NP_001913.2.
DR UCSC; uc001vlv.6; human. [P40126-1]
DR CTD; 1638; -.
DR DisGeNET; 1638; -.
DR GeneCards; DCT; -.
DR HGNC; HGNC:2709; DCT.
DR HPA; ENSG00000080166; Tissue enriched (skin).
DR MalaCards; DCT; -.
DR MIM; 191275; gene.
DR MIM; 619165; phenotype.
DR neXtProt; NX_P40126; -.
DR OpenTargets; ENSG00000080166; -.
DR Orphanet; 597733; Oculocutaneous albinism type 8.
DR PharmGKB; PA27179; -.
DR VEuPathDB; HostDB:ENSG00000080166; -.
DR eggNOG; ENOG502QRNA; Eukaryota.
DR GeneTree; ENSGT00940000156856; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR InParanoid; P40126; -.
DR OMA; RERWPRK; -.
DR OrthoDB; 881347at2759; -.
DR PhylomeDB; P40126; -.
DR TreeFam; TF315865; -.
DR PathwayCommons; P40126; -.
DR Reactome; R-HSA-5662702; Melanin biosynthesis.
DR SignaLink; P40126; -.
DR SIGNOR; P40126; -.
DR UniPathway; UPA00785; -.
DR BioGRID-ORCS; 1638; 12 hits in 1070 CRISPR screens.
DR ChiTaRS; DCT; human.
DR GeneWiki; Dopachrome_tautomerase; -.
DR GenomeRNAi; 1638; -.
DR Pharos; P40126; Tbio.
DR PRO; PR:P40126; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P40126; protein.
DR Bgee; ENSG00000080166; Expressed in upper leg skin and 125 other tissues.
DR ExpressionAtlas; P40126; baseline and differential.
DR Genevisible; P40126; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005507; F:copper ion binding; TAS:ProtInc.
DR GO; GO:0004167; F:dopachrome isomerase activity; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0048468; P:cell development; IEA:Ensembl.
DR GO; GO:0048066; P:developmental pigmentation; IBA:GO_Central.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0006583; P:melanin biosynthetic process from tyrosine; ISS:UniProtKB.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IBA:GO_Central.
DR GO; GO:0009637; P:response to blue light; IDA:UniProtKB.
DR GO; GO:0021847; P:ventricular zone neuroblast division; IBA:GO_Central.
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; Alternative splicing; Disease variant;
KW Glycoprotein; Isomerase; Melanin biosynthesis; Membrane; Metal-binding;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..519
FT /note="L-dopachrome tautomerase"
FT /id="PRO_0000035892"
FT TOPO_DOM 24..472
FT /note="Lumenal, melanosome"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 494..519
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 393
FT /note="V -> VVISNRLLYNATTNILEHVRKEKATKELPSLHVL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:11777994"
FT /id="VSP_043581"
FT VARIANT 40
FT /note="C -> S (in OCA8; dbSNP:rs370729240)"
FT /evidence="ECO:0000269|PubMed:33100333"
FT /id="VAR_085343"
FT VARIANT 61
FT /note="C -> W (in OCA8)"
FT /evidence="ECO:0000269|PubMed:33100333"
FT /id="VAR_085344"
SQ SEQUENCE 519 AA; 59145 MW; AFDDF21768002A89 CRC64;
MSPLWWGFLL SCLGCKILPG AQGQFPRVCM TVDSLVNKEC CPRLGAESAN VCGSQQGRGQ
CTEVRADTRP WSGPYILRNQ DDRELWPRKF FHRTCKCTGN FAGYNCGDCK FGWTGPNCER
KKPPVIRQNI HSLSPQEREQ FLGALDLAKK RVHPDYVITT QHWLGLLGPN GTQPQFANCS
VYDFFVWLHY YSVRDTLLGP GRPYRAIDFS HQGPAFVTWH RYHLLCLERD LQRLIGNESF
ALPYWNFATG RNECDVCTDQ LFGAARPDDP TLISRNSRFS SWETVCDSLD DYNHLVTLCN
GTYEGLLRRN QMGRNSMKLP TLKDIRDCLS LQKFDNPPFF QNSTFSFRNA LEGFDKADGT
LDSQVMSLHN LVHSFLNGTN ALPHSAANDP IFVVLHSFTD AIFDEWMKRF NPPADAWPQE
LAPIGHNRMY NMVPFFPPVT NEELFLTSDQ LGYSYAIDLP VSVEETPGWP TTLLVVMGTL
VALVGLFVLL AFLQYRRLRK GYTPLMETHL SSKRYTEEA
