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   24-JAN-2024, entry version 177.
DE   RecName: Full=L-dopachrome tautomerase {ECO:0000305};
DE            Short=DCT;
DE            Short=DT;
DE            EC=5.3.3.12 {ECO:0000269|PubMed:1537333};
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 {ECO:0000312|MGI:MGI:102563}; Synonyms=Tyrp-2, Tyrp2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN
RP   SLATY, AND VARIANT SLATY GLN-194.
RX   PubMed=1537334; DOI=10.1002/j.1460-2075.1992.tb05083.x;
RA   Jackson I.J., Chambers D.M., Tsukamoto K., Copeland N.G., Gilbert D.J.,
RA   Jenkins N.A., Hearing V.J.;
RT   "A second tyrosinase-related protein, TRP-2, maps to and is mutated at the
RT   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., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98, VARIANT SLATY-2J LEU-434, AND
RP   VARIANT 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 tautomerase
RT   (Tyrp2/Dct) gene and sequence of two novel slaty alleles.";
RL   Genomics 29:35-43(1995).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND GLYCOSYLATION.
RX   PubMed=1537333; DOI=10.1002/j.1460-2075.1992.tb05082.x;
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 termed
RT   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., Garcia-Borron J.C.,
RA   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., Garcia-Borron J.C.,
RA   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 regulates
RT   melanogenic enzyme trafficking in melanocytes.";
RL   J. Biol. Chem. 291:1427-1440(2016).
RN   [9]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-40 AND CYS-61.
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) (PubMed:1537333, PubMed:1537334).
CC       {ECO:0000269|PubMed:1537333, ECO:0000269|PubMed:1537334,
CC       ECO:0000269|PubMed:33100333}.
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, 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: Forms an OPN3-dependent complex with TYR in response to blue
CC       light in melanocytes. {ECO:0000250|UniProtKB:P40126}.
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:P40126}; Single-pass type I membrane protein
CC       {ECO:0000250|UniProtKB:P40126}. Melanosome
CC       {ECO:0000269|PubMed:26620560}. Note=Proper trafficking to melanosome is
CC       regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
CC       {ECO:0000269|PubMed:26620560}.
CC   -!- TISSUE SPECIFICITY: Melanocytes and retinal pigmented epithelium (at
CC       protein level). {ECO:0000269|PubMed:1537334}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:1537333}.
CC   -!- DISEASE: Note=The slaty mutation in Tyrp2 leads to a decrease of DT
CC       activity and a consequent change in the pigmentation of the mice to a
CC       dark gray/brown eumelanin. The slaty-2j mutation has a similar
CC       phenotype, the slaty-lt (light) mutation has a more severe effect and
CC       is semidominant; its phenotype may be a result of the failure of the
CC       enzyme to be correctly targeted to its normal location on the inner
CC       face of the melanosomal membrane. {ECO:0000269|PubMed:1537334,
CC       ECO:0000269|PubMed:8530099}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice show an hypopigmentation of the coat
CC       and have the retinal pigmented epithelium significantly less pigmented
CC       than wild-type retinas. {ECO:0000269|PubMed:33100333}.
CC   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
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; 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   AlphaFoldDB; P29812; -.
DR   SMR; P29812; -.
DR   STRING; 10090.ENSMUSP00000022725; -.
DR   GlyCosmos; P29812; 7 sites, No reported glycans.
DR   GlyGen; P29812; 7 sites.
DR   iPTMnet; P29812; -.
DR   PhosphoSitePlus; P29812; -.
DR   MaxQB; P29812; -.
DR   PaxDb; 10090-ENSMUSP00000022725; -.
DR   ProteomicsDB; 297765; -.
DR   TopDownProteomics; P29812; -.
DR   Antibodypedia; 2252; 475 antibodies from 33 providers.
DR   DNASU; 13190; -.
DR   Ensembl; ENSMUST00000022725.4; ENSMUSP00000022725.3; ENSMUSG00000022129.5.
DR   GeneID; 13190; -.
DR   KEGG; mmu:13190; -.
DR   UCSC; uc007uym.2; mouse.
DR   AGR; MGI:102563; -.
DR   CTD; 1638; -.
DR   MGI; MGI:102563; Dct.
DR   VEuPathDB; HostDB:ENSMUSG00000022129; -.
DR   eggNOG; ENOG502QRNA; Eukaryota.
DR   GeneTree; ENSGT00940000156856; -.
DR   HOGENOM; CLU_038693_1_0_1; -.
DR   InParanoid; P29812; -.
DR   OMA; FFNRTCK; -.
DR   OrthoDB; 70287at2759; -.
DR   PhylomeDB; P29812; -.
DR   TreeFam; TF315865; -.
DR   BioCyc; MetaCyc:X01347-MONOMER; -.
DR   Reactome; R-MMU-5662702; Melanin biosynthesis.
DR   UniPathway; UPA00785; -.
DR   BioGRID-ORCS; 13190; 3 hits in 77 CRISPR screens.
DR   ChiTaRS; Dct; mouse.
DR   PRO; PR:P29812; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; P29812; Protein.
DR   Bgee; ENSMUSG00000022129; Expressed in iris and 127 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR   GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:0007405; P:neuroblast proliferation; IMP:MGI.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:MGI.
DR   GO; GO:0009637; P:response to blue light; ISS:UniProtKB.
DR   GO; GO:0021847; P:ventricular zone neuroblast division; IMP:MGI.
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:SF4; L-DOPACHROME TAUTOMERASE; 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; P29812; MM.
PE   1: Evidence at protein level;
KW   Disease variant; Glycoprotein; Isomerase; Melanin biosynthesis; Membrane;
KW   Metal-binding; Reference proteome; Signal; Transmembrane;
KW   Transmembrane helix; Zinc.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..517
FT                   /note="L-dopachrome tautomerase"
FT                   /id="PRO_0000035893"
FT   TOPO_DOM        24..472
FT                   /note="Lumenal, melanosome"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        473..491
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        492..517
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        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
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   VARIANT         194
FT                   /note="R -> Q (in slaty; decreased DOPAchrome tautomerase
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:1537334"
FT   VARIANT         434
FT                   /note="P -> L (in slaty-2j)"
FT                   /evidence="ECO:0000269|PubMed:8530099"
FT   VARIANT         486
FT                   /note="G -> R (in slaty-lt)"
FT                   /evidence="ECO:0000269|PubMed:8530099"
FT   MUTAGEN         40
FT                   /note="C->S: Mutant mice show an hypopigmentation of the
FT                   coat and have the retinal pigmented epithelium
FT                   significantly less pigmented than wild-type retinas."
FT                   /evidence="ECO:0000269|PubMed:33100333"
FT   MUTAGEN         61
FT                   /note="C->W: Mutant mice show an hypopigmentation of the
FT                   coat and have the retinal pigmented epithelium
FT                   significantly less pigmented than wild-type retinas."
FT                   /evidence="ECO:0000269|PubMed:33100333"
FT   CONFLICT        260..261
FT                   /note="EL -> DW (in Ref. 1; CAA44951)"
FT                   /evidence="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
//