TYRO_MOUSE
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 03-AUG-2022, entry version 199.
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 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). In addition to hydroxylating tyrosine
CC to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of
CC DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-
CC dihydroxyindole) to indole-5,6 quinone (PubMed:1537333).
CC {ECO:0000269|PubMed:1537333, ECO:0000269|PubMed:2517217}.
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 -!- 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";
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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 GlyGen; P11344; 6 sites.
DR PhosphoSitePlus; P11344; -.
DR PaxDb; P11344; -.
DR PRIDE; P11344; -.
DR ProteomicsDB; 298079; -.
DR Antibodypedia; 3663; 881 antibodies from 38 providers.
DR DNASU; 22173; -.
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 VEuPathDB; HostDB:ENSMUSG00000004651; -.
DR eggNOG; ENOG502QRET; Eukaryota.
DR GeneTree; ENSGT00940000155336; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR InParanoid; P11344; -.
DR OMA; HWAPAFS; -.
DR OrthoDB; 881347at2759; -.
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 72 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 tissues.
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: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; -; 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 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
