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Database: UniProt
Entry: P29812
LinkDB: P29812
Original site: P29812 
ID   TYRP2_MOUSE             Reviewed;         517 AA.
AC   P29812; Q6NXI2;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   13-FEB-2019, entry version 151.
DE   RecName: Full=L-dopachrome tautomerase;
DE            Short=DCT;
DE            Short=DT;
DE            EC=5.3.3.12;
DE   AltName: Full=DOPAchrome conversion factor {ECO:0000303|PubMed:1537333};
DE   AltName: Full=DOPAchrome isomerase {ECO:0000303|PubMed:1537333};
DE   AltName: Full=DOPAchrome oxidoreductase {ECO:0000303|PubMed:1537333};
DE   AltName: Full=L-dopachrome Delta-isomerase;
DE   AltName: Full=SLATY locus protein;
DE   AltName: Full=Tyrosinase-related protein 2;
DE            Short=TRP-2;
DE            Short=TRP2;
DE   Flags: Precursor;
GN   Name=Dct; Synonyms=Tyrp-2, Tyrp2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1537334;
RA   Jackson I.J., Chambers D.M., Tsukamoto K., Copeland N.G.,
RA   Gilbert D.J., Jenkins N.A., Hearing V.J.;
RT   "A second tyrosinase-related protein, TRP-2, maps to and is mutated at
RT   the mouse slaty locus.";
RL   EMBO J. 11:527-536(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98, AND VARIANTS SLATY-2J
RP   LEU-434 AND SLATY-LT ARG-486.
RC   STRAIN=129/Sv;
RX   PubMed=8530099; DOI=10.1006/geno.1995.1212;
RA   Budd P.S., Jackson I.J.;
RT   "Structure of the mouse tyrosinase-related protein-2/dopachrome
RT   tautomerase (Tyrp2/Dct) gene and sequence of two novel slaty
RT   alleles.";
RL   Genomics 29:35-43(1995).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND GLYCOSYLATION.
RX   PubMed=1537333;
RA   Tsukamoto K., Jackson I.J., Urabe K., Montague P.M., Hearing V.J.;
RT   "A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme
RT   termed DOPAchrome tautomerase.";
RL   EMBO J. 11:519-526(1992).
RN   [6]
RP   ZINC-BINDING.
RX   PubMed=7980602; DOI=10.1006/bbrc.1994.2596;
RA   Solano F., Martinez-Liarte J.H., Jimenez-Cervantes C.,
RA   Garcia-Borron J.C., Lozano J.A.;
RT   "Dopachrome tautomerase is a zinc-containing enzyme.";
RL   Biochem. Biophys. Res. Commun. 204:1243-1250(1994).
RN   [7]
RP   ZINC-BINDING.
RX   PubMed=8573077; DOI=10.1042/bj3130447;
RA   Solano F., Jimenez-Cervantes C., Martinez-Liarte J.H.,
RA   Garcia-Borron J.C., Jara J.R., Lozano J.A.;
RT   "Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome
RT   tautomerase.";
RL   Biochem. J. 313:447-453(1996).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=26620560; DOI=10.1074/jbc.M115.684043;
RA   Marubashi S., Shimada H., Fukuda M., Ohbayashi N.;
RT   "RUTBC1 functions as a GTPase-activating protein for Rab32/38 and
RT   regulates melanogenic enzyme trafficking in melanocytes.";
RL   J. Biol. Chem. 291:1427-1440(2016).
CC   -!- FUNCTION: Catalyzes the conversion of L-dopachrome into 5,6-
CC       dihydroxyindole-2-carboxylic acid (DHICA) (PubMed:1537333).
CC       Involved in regulating eumelanin and phaeomelanin levels.
CC       {ECO:0000269|PubMed:1537333}.
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:0000269|PubMed:1537333};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:7980602,
CC         ECO:0000269|PubMed:8573077};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:7980602,
CC       ECO:0000269|PubMed:8573077};
CC   -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC   -!- SUBUNIT: Tyrosinase, TYRP1 and DCT/TYRP2 may form a multienzyme
CC       complex.
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:P40126}; Single-pass type I membrane
CC       protein {ECO:0000250|UniProtKB:P40126}. Melanosome
CC       {ECO:0000269|PubMed:26620560}. Note=Proper trafficking to
CC       melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
CC       {ECO:0000269|PubMed:26620560}.
CC   -!- TISSUE SPECIFICITY: Melanocytes and retinal pigmented epithelium.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:1537333}.
CC   -!- DISEASE: Note=The slaty mutation in Tyrp2 leads to a decrease of
CC       DT activity and a consequent change in the pigmentation of the
CC       mice to a dark gray/brown eumelanin. The slaty-2j mutation has a
CC       similar phenotype, the slaty-lt (light) mutation has a more severe
CC       effect and is semidominant; its phenotype may be a result of the
CC       failure of the enzyme to be correctly targeted to its normal
CC       location on the inner face of the melanosomal membrane.
CC       {ECO:0000269|PubMed:8530099}.
CC   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
DR   EMBL; X63349; CAA44951.1; -; mRNA.
DR   EMBL; CT025675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC067064; AAH67064.1; -; mRNA.
DR   EMBL; BC082330; AAH82330.1; -; mRNA.
DR   EMBL; X85126; CAA59440.1; -; Genomic_DNA.
DR   CCDS; CCDS27331.1; -.
DR   PIR; S19243; S19243.
DR   RefSeq; NP_034154.2; NM_010024.3.
DR   UniGene; Mm.19987; -.
DR   ProteinModelPortal; P29812; -.
DR   SMR; P29812; -.
DR   STRING; 10090.ENSMUSP00000022725; -.
DR   iPTMnet; P29812; -.
DR   PhosphoSitePlus; P29812; -.
DR   MaxQB; P29812; -.
DR   PaxDb; P29812; -.
DR   PRIDE; P29812; -.
DR   TopDownProteomics; P29812; -.
DR   Ensembl; ENSMUST00000022725; ENSMUSP00000022725; ENSMUSG00000022129.
DR   GeneID; 13190; -.
DR   KEGG; mmu:13190; -.
DR   UCSC; uc007uym.2; mouse.
DR   CTD; 1638; -.
DR   MGI; MGI:102563; Dct.
DR   eggNOG; ENOG410IEEB; Eukaryota.
DR   eggNOG; ENOG410XSJD; LUCA.
DR   GeneTree; ENSGT00940000156856; -.
DR   HOGENOM; HOG000118376; -.
DR   HOVERGEN; HBG003553; -.
DR   InParanoid; P29812; -.
DR   KO; K01827; -.
DR   OMA; FVVLHSF; -.
DR   OrthoDB; 881347at2759; -.
DR   TreeFam; TF315865; -.
DR   BioCyc; MetaCyc:X01347-MONOMER; -.
DR   Reactome; R-MMU-5662702; Melanin biosynthesis.
DR   UniPathway; UPA00785; -.
DR   ChiTaRS; Dct; mouse.
DR   PRO; PR:P29812; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   Bgee; ENSMUSG00000022129; Expressed in 126 organ(s), highest expression level in iris.
DR   Genevisible; P29812; MM.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR   GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004167; F:dopachrome isomerase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR   GO; GO:0048468; P:cell development; IMP:MGI.
DR   GO; GO:0048066; P:developmental pigmentation; IMP:MGI.
DR   GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR   GO; GO:0006583; P:melanin biosynthetic process from tyrosine; IDA:UniProtKB.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:MGI.
DR   GO; GO:0021847; P:ventricular zone neuroblast division; IMP:MGI.
DR   Gene3D; 1.10.1280.10; -; 1.
DR   InterPro; IPR002227; Tyrosinase_Cu-bd.
DR   InterPro; IPR008922; Unchr_di-copper_centre.
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   Complete proteome; Disease mutation; Glycoprotein; Isomerase;
KW   Melanin biosynthesis; Membrane; Metal-binding; Reference proteome;
KW   Signal; Transmembrane; Transmembrane helix; Zinc.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    517       L-dopachrome tautomerase.
FT                                /FTId=PRO_0000035893.
FT   TOPO_DOM     24    472       Lumenal, melanosome. {ECO:0000255}.
FT   TRANSMEM    473    491       Helical. {ECO:0000255}.
FT   TOPO_DOM    492    517       Cytoplasmic. {ECO:0000255}.
FT   METAL       189    189       Zinc A. {ECO:0000250}.
FT   METAL       211    211       Zinc A. {ECO:0000250}.
FT   METAL       220    220       Zinc A. {ECO:0000250}.
FT   METAL       369    369       Zinc B. {ECO:0000250}.
FT   METAL       373    373       Zinc B. {ECO:0000250}.
FT   METAL       396    396       Zinc B. {ECO:0000250}.
FT   CARBOHYD     92     92       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    170    170       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    178    178       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    237    237       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    300    300       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    342    342       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    377    377       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT     194    194       R -> Q (in slaty).
FT   VARIANT     434    434       P -> L (in slaty-2j).
FT                                {ECO:0000269|PubMed:8530099}.
FT   VARIANT     486    486       G -> R (in slaty-lt).
FT                                {ECO:0000269|PubMed:8530099}.
FT   CONFLICT    260    261       EL -> DW (in Ref. 1; CAA44951).
FT                                {ECO:0000305}.
SQ   SEQUENCE   517 AA;  58510 MW;  BC21FE73BE392CEA CRC64;
     MGLVGWGLLL GCLGCGILLR ARAQFPRVCM TLDGVLNKEC CPPLGPEATN ICGFLEGRGQ
     CAEVQTDTRP WSGPYILRNQ DDREQWPRKF FNRTCKCTGN FAGYNCGGCK FGWTGPDCNR
     KKPAILRRNI HSLTAQEREQ FLGALDLAKK SIHPDYVITT QHWLGLLGPN GTQPQIANCS
     VYDFFVWLHY YSVRDTLLGP GRPYKAIDFS HQGPAFVTWH RYHLLWLERE LQRLTGNESF
     ALPYWNFATG KNECDVCTDE LLGAARQDDP TLISRNSRFS TWEIVCDSLD DYNRRVTLCN
     GTYEGLLRRN KVGRNNEKLP TLKNVQDCLS LQKFDSPPFF QNSTFSFRNA LEGFDKADGT
     LDSQVMNLHN LAHSFLNGTN ALPHSAANDP VFVVLHSFTD AIFDEWLKRN NPSTDAWPQE
     LAPIGHNRMY NMVPFFPPVT NEELFLTAEQ LGYNYAVDLS EEEAPVWSTT LSVVIGILGA
     FVLLLGLLAF LQYRRLRKGY APLMETGLSS KRYTEEA
//
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