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Database: UniProt
Entry: P11344
LinkDB: P11344
Original site: P11344 
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   13-FEB-2019, entry version 180.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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
RT   melanotropin on its gene expression.";
RL   Biochem. Biophys. Res. Commun. 153:1301-1309(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=3141148;
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].
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
RT   mouse 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.,
RA   Francke U., Lamoreux M.L., Whitney J.B. III, Halaban R.;
RT   "Isolation, chromosomal mapping, and expression of the mouse
RT   tyrosinase 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
RT   causing the 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;
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   [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
RT   regulates melanogenic enzyme trafficking in melanocytes.";
RL   J. Biol. Chem. 291:1427-1440(2016).
RN   [11]
RP   VARIANT CHINCHILLA MICE THR-482.
RX   PubMed=2118105;
RA   Beermann F., Ruppert S., Hummler E., Bosch F.X., Mueller G.,
RA   Ruether U., Schuetz G.;
RT   "Rescue of the albino phenotype by introduction of a functional
RT   tyrosinase gene into mice.";
RL   EMBO J. 9:2819-2826(1990).
CC   -!- FUNCTION: This is a copper-containing oxidase that functions in
CC       the formation of pigments such as melanins and other polyphenolic
CC       compounds. Catalyzes the initial and rate limiting step in the
CC       cascade of reactions leading to melanin production from tyrosine.
CC       In addition to hydroxylating tyrosine to DOPA (3,4-
CC       dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to
CC       DOPA-quinone, and possibly the oxidation of DHI (5,6-
CC       dihydroxyindole) to indole-5,6 quinone (PubMed:2494997,
CC       PubMed:2517217, PubMed:1537333). {ECO:0000269|PubMed:1537333,
CC       ECO:0000269|PubMed:2494997, ECO:0000269|PubMed:2517217}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone;
CC         Xref=Rhea:RHEA:34287, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57504, 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;
CC         Xref=Rhea:RHEA:18117, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57924, ChEBI:CHEBI:58315; EC=1.14.18.1;
CC         Evidence={ECO:0000269|PubMed:1537333};
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC       Note=Binds 2 copper ions per subunit.
CC       {ECO:0000250|UniProtKB:Q9ZP19};
CC   -!- INTERACTION:
CC       P07147:Tyrp1; NbExp=2; IntAct=EBI-821603, EBI-821614;
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:P14679}; Single-pass type I membrane
CC       protein {ECO:0000250|UniProtKB:P14679}. 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   -!- 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
CC       49 of August 2004;
CC       URL="https://web.expasy.org/spotlight/back_issues/049";
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   UniGene; Mm.238127; -.
DR   ProteinModelPortal; P11344; -.
DR   SMR; P11344; -.
DR   BioGrid; 204394; 7.
DR   ELM; P11344; -.
DR   IntAct; P11344; 1.
DR   STRING; 10090.ENSMUSP00000004770; -.
DR   BindingDB; P11344; -.
DR   ChEMBL; CHEMBL5346; -.
DR   PhosphoSitePlus; P11344; -.
DR   PaxDb; P11344; -.
DR   PRIDE; P11344; -.
DR   Ensembl; ENSMUST00000004770; ENSMUSP00000004770; ENSMUSG00000004651.
DR   GeneID; 22173; -.
DR   KEGG; mmu:22173; -.
DR   UCSC; uc009ifo.1; mouse.
DR   CTD; 7299; -.
DR   MGI; MGI:98880; Tyr.
DR   eggNOG; ENOG410IEZU; Eukaryota.
DR   eggNOG; ENOG410Y42I; LUCA.
DR   GeneTree; ENSGT00940000155336; -.
DR   HOGENOM; HOG000118376; -.
DR   HOVERGEN; HBG003553; -.
DR   InParanoid; P11344; -.
DR   KO; K00505; -.
DR   OMA; PNCTEKR; -.
DR   OrthoDB; 881347at2759; -.
DR   PhylomeDB; P11344; -.
DR   TreeFam; TF315865; -.
DR   BRENDA; 1.14.18.1; 3474.
DR   Reactome; R-MMU-5662702; Melanin biosynthesis.
DR   PRO; PR:P11344; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; ENSMUSG00000004651; Expressed in 82 organ(s), highest expression level in iris.
DR   ExpressionAtlas; P11344; baseline and differential.
DR   Genevisible; P11344; MM.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0016021; C:integral component of membrane; TAS: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:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR   GO; GO:0004503; F:monophenol monooxygenase activity; ISO:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
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:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0009411; P:response to UV; IBA:GO_Central.
DR   GO; GO:0033280; P:response to vitamin D; IBA:GO_Central.
DR   GO; GO:0048538; P:thymus development; 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   Albinism; Complete proteome; Copper; Disease mutation; Glycoprotein;
KW   Melanin biosynthesis; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     18       {ECO:0000255}.
FT   CHAIN        19    533       Tyrosinase.
FT                                /FTId=PRO_0000035880.
FT   TOPO_DOM     19    476       Lumenal, melanosome. {ECO:0000255}.
FT   TRANSMEM    477    497       Helical. {ECO:0000255}.
FT   TOPO_DOM    498    533       Cytoplasmic. {ECO:0000255}.
FT   COMPBIAS    503    508       Poly-Lys.
FT   METAL       180    180       Copper A. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   METAL       202    202       Copper A. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   METAL       211    211       Copper A. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   METAL       363    363       Copper B. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   METAL       367    367       Copper B. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   METAL       390    390       Copper B. {ECO:0000250|UniProtKB:Q9ZP19}.
FT   CARBOHYD     86     86       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    111    111       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    161    161       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    230    230       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    337    337       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    371    371       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT     103    103       C -> S (in albino mice).
FT                                {ECO:0000269|PubMed:2110899,
FT                                ECO:0000269|PubMed:2507645,
FT                                ECO:0000269|PubMed:3134020}.
FT   VARIANT     420    420       H -> R (in strain: Himalayan).
FT                                {ECO:0000269|PubMed:2567165}.
FT   VARIANT     482    482       A -> T (in chinchilla mice).
FT                                {ECO:0000269|PubMed:2118105}.
FT   CONFLICT     40     40       M -> I (in Ref. 4; AAA37806).
FT                                {ECO:0000305}.
FT   CONFLICT    197    197       D -> Q (in Ref. 4; AAA37806).
FT                                {ECO:0000305}.
FT   CONFLICT    264    264       S -> I (in Ref. 3; CAA31273).
FT                                {ECO:0000305}.
FT   CONFLICT    346    346       G -> V (in Ref. 2; AAA40516).
FT                                {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
//
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