TYRP2_MOUSE
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 03-AUG-2022, entry version 169.
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, AND VARIANTS SLATY-2J LEU-434
RP 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 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}.
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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 GlyGen; P29812; 7 sites.
DR iPTMnet; P29812; -.
DR PhosphoSitePlus; P29812; -.
DR MaxQB; P29812; -.
DR PaxDb; P29812; -.
DR PRIDE; P29812; -.
DR ProteomicsDB; 297765; -.
DR TopDownProteomics; P29812; -.
DR Antibodypedia; 2252; 430 antibodies from 33 providers.
DR DNASU; 13190; -.
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 VEuPathDB; HostDB:ENSMUSG00000022129; -.
DR eggNOG; ENOG502QRNA; Eukaryota.
DR GeneTree; ENSGT00940000156856; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR InParanoid; P29812; -.
DR OMA; RERWPRK; -.
DR OrthoDB; 881347at2759; -.
DR PhylomeDB; P29812; -.
DR TreeFam; TF315865; -.
DR BioCyc; MetaCyc:X01347-MON; -.
DR Reactome; R-MMU-5662702; Melanin biosynthesis.
DR UniPathway; UPA00785; -.
DR BioGRID-ORCS; 13190; 3 hits in 72 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 125 other tissues.
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: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; -; 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 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
