ID   TYRO_MOUSE              Reviewed;         533 AA.
AC   P11344;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2007, sequence version 3.
DT   27-MAR-2024, entry version 208.
DE   RecName: Full=Tyrosinase;
DE            EC=1.14.18.1;
DE   AltName: Full=Albino locus protein;
DE   AltName: Full=Monophenol monooxygenase;
DE   Flags: Precursor;
GN   Name=Tyr;
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].
RC   STRAIN=C57BL/6J;
RA   Yamamoto H., Takeuchi S., Kudo T., Makino K., Nakata A., Shinoda T.,
RA   Takeuchi T.;
RT   "Cloning and sequencing of mouse tyrosinase cDNA.";
RL   Jpn. J. Genet. 62:271-274(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-103.
RC   STRAIN=DBA/2J;
RX   PubMed=3134020; DOI=10.1016/s0006-291x(88)81370-6;
RA   Kwon B.S., Wakulchik M., Haq A.K., Halaban R., Kestler D.;
RT   "Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin
RT   on its gene expression.";
RL   Biochem. Biophys. Res. Commun. 153:1301-1309(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=3141148; DOI=10.1002/j.1460-2075.1988.tb03126.x;
RA   Mueller G., Ruppert S., Schmid E., Schuetz G.;
RT   "Functional analysis of alternatively spliced tyrosinase gene
RT   transcripts.";
RL   EMBO J. 7:2723-2730(1988).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-420.
RC   STRAIN=Himalayan;
RX   PubMed=2567165; DOI=10.1016/0006-291x(89)91588-x;
RA   Kwon B.S., Halaban R., Chintamaneni C.;
RT   "Molecular basis of mouse Himalayan mutation.";
RL   Biochem. Biophys. Res. Commun. 161:252-260(1989).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=2494997; DOI=10.1016/0006-291x(89)90072-7;
RA   Terao M., Tabe L., Garattini E., Sartori D., Studer M., Mintz B.;
RT   "Isolation and characterization of variant cDNAs encoding mouse
RT   tyrosinase.";
RL   Biochem. Biophys. Res. Commun. 159:848-853(1989).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-273, AND FUNCTION.
RX   PubMed=2517217; DOI=10.1266/jjg.64.121;
RA   Yamamoto H., Takeuchi S., Kudo T., Sato C., Takeuchi T.;
RT   "Melanin production in cultured albino melanocytes transfected with mouse
RT   tyrosinase cDNA.";
RL   Jpn. J. Genet. 64:121-135(1989).
RN   [7]
RP   NUCLEOTIDE SEQUENCE OF 1-273, AND VARIANT ALBINO SER-103.
RC   STRAIN=BALB/cJ;
RX   PubMed=2507645; DOI=10.1111/1523-1747.ep12319693;
RA   Kwon B.S., Haq A.K., Wakulchik M., Kestler D., Barton D.E., Francke U.,
RA   Lamoreux M.L., Whitney J.B. III, Halaban R.;
RT   "Isolation, chromosomal mapping, and expression of the mouse tyrosinase
RT   gene.";
RL   J. Invest. Dermatol. 93:589-594(1989).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-13, AND VARIANT ALBINO SER-103.
RC   STRAIN=BALB/cJ;
RX   PubMed=2110899; DOI=10.1111/j.1432-1033.1990.tb15510.x;
RA   Shibahara S., Okinaga S., Tomita Y., Takeda A., Yamamoto H., Sato M.,
RA   Takeuchi T.;
RT   "A point mutation in the tyrosinase gene of BALB/c albino mouse causing the
RT   cysteine-->serine substitution at position 85.";
RL   Eur. J. Biochem. 189:455-461(1990).
RN   [9]
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   [10]
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   [11]
RP   FUNCTION.
RX   PubMed=35469906; DOI=10.1016/j.jid.2022.04.008;
RA   Liu Y., Chi W., Tao L., Wang G., Deepak R.N.V.K., Sheng L., Chen T.,
RA   Feng Y., Cao X., Cheng L., Zhao X., Liu X., Deng H., Fan H., Jiang P.,
RA   Chen L.;
RT   "Ablation of H+/glucose Exporter SLC45A2 Enhances Melanosomal Glycolysis to
RT   Inhibit Melanin Biosynthesis and Promote Melanoma Metastasis.";
RL   J. Invest. Dermatol. 0:0-0(2022).
RN   [12]
RP   VARIANT CHINCHILLA MICE THR-482.
RX   PubMed=2118105; DOI=10.1002/j.1460-2075.1990.tb07470.x;
RA   Beermann F., Ruppert S., Hummler E., Bosch F.X., Mueller G., Ruether U.,
RA   Schuetz G.;
RT   "Rescue of the albino phenotype by introduction of a functional tyrosinase
RT   gene into mice.";
RL   EMBO J. 9:2819-2826(1990).
CC   -!- FUNCTION: This is a copper-containing oxidase that functions in the
CC       formation of pigments such as melanins and other polyphenolic compounds
CC       (PubMed:2517217). Catalyzes the initial and rate limiting step in the
CC       cascade of reactions leading to melanin production from tyrosine
CC       (PubMed:2517217, PubMed:1537333, PubMed:35469906). In addition to
CC       hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also
CC       catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the
CC       oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone
CC       (PubMed:1537333). {ECO:0000269|PubMed:1537333,
CC       ECO:0000269|PubMed:2517217, ECO:0000269|PubMed:35469906}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504,
CC         ChEBI:CHEBI:57924; EC=1.14.18.1;
CC         Evidence={ECO:0000269|PubMed:1537333};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924,
CC         ChEBI:CHEBI:58315; EC=1.14.18.1;
CC         Evidence={ECO:0000269|PubMed:1537333};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 H2O + 2
CC         indole-5,6-quinone-2-carboxylate; Xref=Rhea:RHEA:68388,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16875,
CC         ChEBI:CHEBI:177869; Evidence={ECO:0000250|UniProtKB:P14679};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68389;
CC         Evidence={ECO:0000250|UniProtKB:P14679};
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC       Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19};
CC   -!- SUBUNIT: Forms an OPN3-dependent complex with DCT in response to blue
CC       light in melanocytes. {ECO:0000250|UniProtKB:P14679}.
CC   -!- INTERACTION:
CC       P11344; P07147: Tyrp1; NbExp=8; IntAct=EBI-821603, EBI-821614;
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:P14679}; Single-pass type I membrane protein
CC       {ECO:0000250|UniProtKB:P14679}. 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: Expressed in the skin.
CC       {ECO:0000269|PubMed:2494997}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:1537333}.
CC   -!- DISEASE: Note=Defects in Tyr result in various forms of albinism.
CC       Himalayan strain tyrosinase is temperature-sensitive.
CC       {ECO:0000269|PubMed:2110899, ECO:0000269|PubMed:2118105,
CC       ECO:0000269|PubMed:2507645, ECO:0000269|PubMed:2567165}.
CC   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA00079.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Snowy stardom - Issue 49 of
CC       August 2004;
CC       URL="https://web.expasy.org/spotlight/back_issues/049";
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; D00440; BAA00341.1; -; mRNA.
DR   EMBL; D00131; BAA00079.1; ALT_SEQ; mRNA.
DR   EMBL; M20234; AAA40516.1; -; mRNA.
DR   EMBL; X12782; CAA31273.1; -; mRNA.
DR   EMBL; M26729; AAA37806.1; -; mRNA.
DR   EMBL; M24560; AAA40517.1; -; mRNA.
DR   EMBL; D00439; BAA00340.1; -; Genomic_DNA.
DR   EMBL; X51743; CAA36033.1; -; Genomic_DNA.
DR   CCDS; CCDS52304.1; -.
DR   PIR; A27711; YRMSCS.
DR   RefSeq; NP_035791.1; NM_011661.5.
DR   AlphaFoldDB; P11344; -.
DR   SMR; P11344; -.
DR   BioGRID; 204394; 8.
DR   ELM; P11344; -.
DR   IntAct; P11344; 2.
DR   STRING; 10090.ENSMUSP00000004770; -.
DR   BindingDB; P11344; -.
DR   ChEMBL; CHEMBL5346; -.
DR   DrugCentral; P11344; -.
DR   GlyCosmos; P11344; 6 sites, No reported glycans.
DR   GlyGen; P11344; 6 sites.
DR   PhosphoSitePlus; P11344; -.
DR   PaxDb; 10090-ENSMUSP00000004770; -.
DR   ProteomicsDB; 298079; -.
DR   Antibodypedia; 3663; 982 antibodies from 38 providers.
DR   DNASU; 22173; -.
DR   Ensembl; ENSMUST00000004770.7; ENSMUSP00000004770.6; ENSMUSG00000004651.7.
DR   GeneID; 22173; -.
DR   KEGG; mmu:22173; -.
DR   UCSC; uc009ifo.1; mouse.
DR   AGR; MGI:98880; -.
DR   CTD; 7299; -.
DR   MGI; MGI:98880; Tyr.
DR   VEuPathDB; HostDB:ENSMUSG00000004651; -.
DR   eggNOG; ENOG502QRET; Eukaryota.
DR   GeneTree; ENSGT00940000155336; -.
DR   HOGENOM; CLU_038693_1_0_1; -.
DR   InParanoid; P11344; -.
DR   OMA; MEAEDYQ; -.
DR   OrthoDB; 70287at2759; -.
DR   PhylomeDB; P11344; -.
DR   TreeFam; TF315865; -.
DR   BRENDA; 1.14.18.1; 3474.
DR   Reactome; R-MMU-5662702; Melanin biosynthesis.
DR   BioGRID-ORCS; 22173; 3 hits in 77 CRISPR screens.
DR   ChiTaRS; Tyr; mouse.
DR   PRO; PR:P11344; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; P11344; Protein.
DR   Bgee; ENSMUSG00000004651; Expressed in iris and 55 other cell types or tissues.
DR   ExpressionAtlas; P11344; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
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:0016020; C:membrane; TAS:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0004503; F:tyrosinase activity; ISO:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0009637; P:response to blue light; ISS:UniProtKB.
DR   GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0009411; P:response to UV; IEA:Ensembl.
DR   GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR   GO; GO:0048538; P:thymus development; 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:SF124; TYROSINASE; 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; P11344; MM.
PE   1: Evidence at protein level;
KW   Albinism; Copper; Disease variant; Glycoprotein; Melanin biosynthesis;
KW   Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..533
FT                   /note="Tyrosinase"
FT                   /id="PRO_0000035880"
FT   TOPO_DOM        19..476
FT                   /note="Lumenal, melanosome"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        477..497
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        498..533
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   BINDING         180
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         202
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         211
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         363
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         367
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         390
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   CARBOHYD        86
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        111
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        371
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         103
FT                   /note="C -> S (in albino mice)"
FT                   /evidence="ECO:0000269|PubMed:2110899,
FT                   ECO:0000269|PubMed:2507645, ECO:0000269|PubMed:3134020"
FT   VARIANT         420
FT                   /note="H -> R (in strain: Himalayan)"
FT                   /evidence="ECO:0000269|PubMed:2567165"
FT   VARIANT         482
FT                   /note="A -> T (in chinchilla mice)"
FT                   /evidence="ECO:0000269|PubMed:2118105"
FT   CONFLICT        40
FT                   /note="M -> I (in Ref. 4; AAA37806)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197
FT                   /note="D -> Q (in Ref. 4; AAA37806)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        264
FT                   /note="S -> I (in Ref. 3; CAA31273)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        346
FT                   /note="G -> V (in Ref. 2; AAA40516)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   533 AA;  60606 MW;  A4C109A97CBD5D6A CRC64;
     MFLAVLYCLL WSFQISDGHF PRACASSKNL LAKECCPPWM GDGSPCGQLS GRGSCQDILL
     SSAPSGPQFP FKGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFGGP NCTEKRVLIR
     RNIFDLSVSE KNKFFSYLTL AKHTISSVYV IPTGTYGQMN NGSTPMFNDI NIYDLFVWMH
     YYVSRDTLLG GSEIWRDIDF AHEAPGFLPW HRLFLLLWEQ EIRELTGDEN FTVPYWDWRD
     AENCDICTDE YLGGRHPENP NLLSPASFFS SWQIICSRSE EYNSHQVLCD GTPEGPLLRN
     PGNHDKAKTP RLPSSADVEF CLSLTQYESG SMDRTANFSF RNTLEGFASP LTGIADPSQS
     SMHNALHIFM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLLEV YPEANAPIGH
     NRDSYMVPFI PLYRNGDFFI TSKDLGYDYS YLQESDPGFY RNYIEPYLEQ ASRIWPWLLG
     AALVGAVIAA ALSGLSSRLC LQKKKKKKQP QEERQPLLMD KDDYHSLLYQ SHL
//