ID   TYRO_PELNI              Reviewed;         532 AA.
AC   Q04604;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   03-MAY-2023, entry version 93.
DE   RecName: Full=Tyrosinase {ECO:0000305};
DE            EC=1.14.18.1 {ECO:0000250|UniProtKB:Q0MVP0};
DE   AltName: Full=Monophenol monooxygenase {ECO:0000305};
DE   Flags: Precursor;
GN   Name=TYR; Synonyms=TYRS;
OS   Pelophylax nigromaculatus (Black-spotted frog) (Rana nigromaculata).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Neobatrachia; Ranoidea; Ranidae; Pelophylax.
OX   NCBI_TaxID=8409;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1446833; DOI=10.1016/0378-1119(92)90144-e;
RA   Takase M., Miura I., Nakata A., Takeuchi T., Nishioka M.;
RT   "Cloning and sequencing of the cDNA encoding tyrosinase of the Japanese
RT   pond frog, Rana nigromaculata.";
RL   Gene 121:359-363(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-277.
RC   TISSUE=Blood;
RX   PubMed=7772385; DOI=10.1266/jjg.70.79;
RA   Miura I., Okumoto H., Makino K., Nakata A., Nishioka M.;
RT   "Analysis of the tyrosinase gene of the Japanese pond frog, Rana
RT   nigromaculata: cloning and nucleotide sequence of the genomic DNA
RT   containing the tyrosinase gene and its flanking regions.";
RL   Jpn. J. Genet. 70:79-92(1995).
CC   -!- FUNCTION: This is a copper-containing oxidase that functions in the
CC       formation of pigments such as melanins and other polyphenolic compounds
CC       (By similarity). Catalyzes the initial and rate limiting step in the
CC       cascade of reactions leading to melanin production from tyrosine. In
CC       addition to hydroxylating tyrosine to DOPA (3,4-
CC       dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-
CC       quinone (By similarity). {ECO:0000250|UniProtKB:P11344,
CC       ECO:0000250|UniProtKB:Q0MVP0}.
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:0000250|UniProtKB:Q0MVP0};
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:0000250|UniProtKB:Q0MVP0};
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   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:Q0MVP0, ECO:0000255}; Single-pass type I
CC       membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
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DR   EMBL; D12514; BAA02077.1; -; mRNA.
DR   EMBL; D37779; BAA07034.1; -; Genomic_DNA.
DR   PIR; JC1392; JC1392.
DR   AlphaFoldDB; Q04604; -.
DR   SMR; Q04604; -.
DR   GlyCosmos; Q04604; 6 sites, No reported glycans.
DR   GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR   GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR   GO; GO:0004503; F:tyrosinase activity; ISS:UniProtKB.
DR   GO; GO:0006583; P:melanin biosynthetic process from tyrosine; ISS:UniProtKB.
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.
PE   2: Evidence at transcript level;
KW   Copper; Glycoprotein; Melanin biosynthesis; Membrane; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..532
FT                   /note="Tyrosinase"
FT                   /id="PRO_0000035884"
FT   TOPO_DOM        20..475
FT                   /note="Lumenal, melanosome"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        476..499
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        500..532
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   BINDING         184
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         206
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         215
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
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         371
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         394
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   CARBOHYD        90
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        341
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        375
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         10
FT                   /note="T -> A"
SQ   SEQUENCE   532 AA;  60116 MW;  B27D3080F0C74B3A CRC64;
     MESTTVLLAT STLLLVLHAS YGQFPRACST AQVLLSKECC PVWPGDNSSC GEVSGRGVCQ
     DVVPSNSPVG AQFPFSGIDD RENWPIVFYN RTCQCQGNFM GYNCGECRFG YTGPNCTVRR
     NMIRKDIFRM TTAEKDKLIA YLNLAKHTIS PDYVIATGTY EQMNNGSNPM FADISAYDLF
     VWIHYYASRD AFLEDGSVWA DIDFAHEAPG FLPWHRFYLL LWEREIQKVT GDDNFTIPFW
     DWRDAQQCEL CTDEFFGGTH PTSNNLLSPA SFFSSWQIIC SRPEEYNSLR IICNGTNEGP
     LLRSPGRHDR NRTPRLPTSA DVEACLSLTD YETGAMDRSA NFSFRNTLEG FAVPTSGIAN
     RSQSSMHNSL HVFLNGSMSS VQGSANDPIF VLHHAFVDSL FEQWLRRHQP SLDVYPEANA
     PVGHNREYNM VPFIPLFTNG EFFVQSRDLG YDYDYLAESG SIEDFLLPYL EQARQIWQWL
     LGAAVLGGLI TAVIATIISL TCRRKRKTKI SEETRPLLME AEDYQATYQS NL
//