ID   TYRO_NEUCR              Reviewed;         685 AA.
AC   P00440; Q6MGJ7; Q7RVL7;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   04-DEC-2007, sequence version 5.
DT   27-MAR-2024, entry version 138.
DE   RecName: Full=Tyrosinase;
DE            EC=1.14.18.1;
DE   AltName: Full=Monophenol monooxygenase;
DE   Flags: Precursor;
GN   Name=T; ORFNames=90C4.150, NCU00776;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Oak Ridge, and TS;
RX   PubMed=2529259; DOI=10.1016/s0021-9258(18)71485-3;
RA   Kupper U., Niedermann D.M., Travaglini G., Lerch K.;
RT   "Isolation and characterization of the tyrosinase gene from Neurospora
RT   crassa.";
RL   J. Biol. Chem. 264:17250-17258(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12655011; DOI=10.1093/nar/gkg293;
RA   Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA   Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT   "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT   genome sequence.";
RL   Nucleic Acids Res. 31:1944-1954(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
RN   [4]
RP   PROTEIN SEQUENCE OF 2-408, AND ACETYLATION AT SER-2.
RC   STRAIN=TL;
RX   PubMed=6210696; DOI=10.1016/s0021-9258(20)65157-2;
RA   Lerch K.;
RT   "Primary structure of tyrosinase from Neurospora crassa. II. Complete amino
RT   acid sequence and chemical structure of a tripeptide containing an unusual
RT   thioether.";
RL   J. Biol. Chem. 257:6414-6419(1982).
RN   [5]
RP   PROTEIN SEQUENCE OF 2-408.
RC   STRAIN=Sing, and TS;
RX   PubMed=6210697; DOI=10.1016/s0021-9258(20)65158-4;
RA   Ruegg C., Ammer D., Lerch K.;
RT   "Comparison of amino acid sequence and thermostability of tyrosinase from
RT   three wild type strains of Neurospora crassa.";
RL   J. Biol. Chem. 257:6420-6426(1982).
CC   -!- FUNCTION: This is a copper-containing oxidase that functions in the
CC       formation of pigments such as melanins and other polyphenolic
CC       compounds.
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   -!- 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   -!- 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   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA33618.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAA33619.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=EAA35696.3; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; M32843; AAA33619.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; M33271; AAA33618.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; BX842680; CAE81941.1; -; Genomic_DNA.
DR   EMBL; CM002236; EAA35696.3; ALT_SEQ; Genomic_DNA.
DR   PIR; A34460; YRNC.
DR   RefSeq; XP_964932.3; XM_959839.3.
DR   AlphaFoldDB; P00440; -.
DR   SMR; P00440; -.
DR   STRING; 367110.P00440; -.
DR   iPTMnet; P00440; -.
DR   PaxDb; 5141-EFNCRP00000000584; -.
DR   EnsemblFungi; EAA35696; EAA35696; NCU00776.
DR   GeneID; 3881081; -.
DR   KEGG; ncr:NCU00776; -.
DR   HOGENOM; CLU_013691_3_1_1; -.
DR   InParanoid; P00440; -.
DR   OrthoDB; 1908494at2759; -.
DR   Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004503; F:tyrosinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.310.20; -; 1.
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; IPR016216; Monophenol_mOase_fun.
DR   InterPro; IPR041640; Tyrosinase_C.
DR   InterPro; IPR002227; Tyrosinase_Cu-bd.
DR   PANTHER; PTHR11474:SF132; TYROSINASE; 1.
DR   PANTHER; PTHR11474; TYROSINASE FAMILY MEMBER; 1.
DR   Pfam; PF18132; Tyosinase_C; 1.
DR   Pfam; PF00264; Tyrosinase; 1.
DR   PIRSF; PIRSF000340; MPO_fungal; 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   1: Evidence at protein level;
KW   Acetylation; Copper; Direct protein sequencing; Melanin biosynthesis;
KW   Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW   Thioether bond.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:6210696,
FT                   ECO:0000269|PubMed:6210697"
FT   CHAIN           2..408
FT                   /note="Tyrosinase"
FT                   /id="PRO_0000035895"
FT   PROPEP          409..685
FT                   /note="Could be involved in enzyme activation"
FT                   /id="PRO_0000035896"
FT   BINDING         67
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         97
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         106
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         278
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         282
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         307
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000269|PubMed:6210696"
FT   CROSSLNK        95..97
FT                   /note="2'-(S-cysteinyl)-histidine (Cys-His)"
FT   VARIANT         15
FT                   /note="P -> T (in strain: Sing, TL and TS)"
FT   VARIANT         30
FT                   /note="D -> E (in strain: Sing)"
FT   VARIANT         130
FT                   /note="V -> T (in strain: Sing)"
FT   VARIANT         202
FT                   /note="D -> N (in strain: TL)"
FT   VARIANT         346..347
FT                   /note="KS -> QN (in strain: Sing)"
FT   VARIANT         371
FT                   /note="I -> T (in strain: Sing)"
FT   VARIANT         424
FT                   /note="K -> N (in strain: TS)"
FT   VARIANT         450
FT                   /note="K -> R (in strain: TS)"
FT   VARIANT         678
FT                   /note="G -> R (in strain: TS)"
FT   CONFLICT        235
FT                   /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   685 AA;  75886 MW;  DF64B764BFF5468A CRC64;
     MSTDIKFAIT GVPTPPSSNG AVPLRRELRD LQQNYPEQFN LYLLGLRDFQ GLDEAKLDSY
     YQVAGIHGMP FKPWAGVPSD TDWSQPGSSG FGGYCTHSSI LFITWHRPYL ALYEQALYAS
     VQAVAQKFPV EGGLRAKYVA AAKDFRAPYF DWASQPPKGT LAFPESLSSR TIQVVDVDGK
     TKSINNPLHR FTFHPVNPSP GDFSAAWSRY PSTVRYPNRL TGASRDERIA PILANELASL
     RNNVSLLLLS YKDFDAFSYN RWDPNTNPGD FGSLEDVHNE IHDRTGGNGH MSSLEVSAFD
     PLFWLHHVNV DRLWSIWQDL NPNSFMTPRP APYSTFVAQE GESQSKSTPL EPFWDKSAAN
     FWTSEQVKDS ITFGYAYPET QKWKYSSVKE YQAAIRKSVT ALYGSNVFAN FVENVADRTP
     ALKKPQATGE ESKSTVSAAA AHAVELSGAK KVAEKVHNVF QHAEEKAQKP VVPVKDTKAE
     SSTAAGMMIG LSIKRPSKLT ASPGPIPESL KYLAPDGKYT DWIVNVRAQK HGLGQSFRVI
     VFLGEFNPDP ETWDDEFNCV GRVSVLGRSA ETQCGKCRKD NANGLIVSGT VPLTSALLQD
     IVGGELQSLK PEDVIPHLRA NLKWKVALFN GDEYNLEEVP DLKVSVASTE VTIDEEGLPH
     YSRQYTVYPE ITEGKPCGHG PEDHI
//