ID TYRP1_BOVIN Reviewed; 537 AA.
AC Q8WN57;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 08-NOV-2023, entry version 117.
DE RecName: Full=5,6-dihydroxyindole-2-carboxylic acid oxidase;
DE Short=DHICA oxidase;
DE EC=1.14.18.-;
DE AltName: Full=Tyrosinase-related protein 1;
DE Short=TRP-1;
DE Short=TRP1;
DE Flags: Precursor;
GN Name=TYRP1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RA Guibert S., Julien R., Oulmouden A.;
RT "Transcriptional regulation of bovine TYRP1 gene.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays a role in melanin biosynthesis. Catalyzes the oxidation
CC of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-
CC quinone-2-carboxylic acid. May regulate or influence the type of
CC melanin synthesized. Also to a lower extent, capable of hydroxylating
CC tyrosine and producing melanin. {ECO:0000250|UniProtKB:P07147}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 H2O + 2 indole-
CC 5,6-quinone-2-carboxylate; Xref=Rhea:RHEA:68388, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16875, ChEBI:CHEBI:177869;
CC Evidence={ECO:0000250|UniProtKB:P17643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68389;
CC Evidence={ECO:0000250|UniProtKB:P17643};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000250|UniProtKB:P17643};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P17643};
CC Note=Contains bound zinc ions after heterologous expression in insect
CC cells. {ECO:0000250|UniProtKB:P17643};
CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC {ECO:0000250|UniProtKB:P17643}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with ATP7A (By similarity).
CC Interacts with SLC45A2 (By similarity). {ECO:0000250|UniProtKB:P07147,
CC ECO:0000250|UniProtKB:P17643}.
CC -!- SUBCELLULAR LOCATION: Melanosome membrane
CC {ECO:0000250|UniProtKB:P07147}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P07147}. Note=Located to mature stage III and IV
CC melanosomes and apposed endosomal tubular membranes. Transported to
CC pigmented melanosomes by the BLOC-1 complex. Proper trafficking to
CC melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
CC {ECO:0000250|UniProtKB:P07147}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P07147}.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC -!- CAUTION: The precise function of this protein in melanin biosynthesis
CC is still under debate. DHICA oxidase activity is controversial. The
CC mouse protein has been shown to have DHICA oxidase activity (By
CC similarity). In contrast, the human protein was shown lack DHICA
CC oxidase activity, or to have DHICA oxidase activity only in the
CC presence of Cu(2+), but not with Zn(2+) (By similarity).
CC {ECO:0000250|UniProtKB:P07147, ECO:0000250|UniProtKB:P17643,
CC ECO:0000305}.
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DR EMBL; AF445638; AAL38167.2; -; mRNA.
DR RefSeq; NP_776905.2; NM_174480.3.
DR AlphaFoldDB; Q8WN57; -.
DR SMR; Q8WN57; -.
DR STRING; 9913.ENSBTAP00000027945; -.
DR GlyCosmos; Q8WN57; 6 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000027945; -.
DR GeneID; 282105; -.
DR KEGG; bta:282105; -.
DR CTD; 7306; -.
DR eggNOG; ENOG502QRNA; Eukaryota.
DR InParanoid; Q8WN57; -.
DR UniPathway; UPA00785; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0097708; C:intracellular vesicle; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004503; F:tyrosinase activity; ISS:UniProtKB.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:0032438; P:melanosome organization; IBA:GO_Central.
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:SF3; 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID OXIDASE; 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 Albinism; Copper; Disulfide bond; Glycoprotein; Melanin biosynthesis;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000250"
FT CHAIN 25..537
FT /note="5,6-dihydroxyindole-2-carboxylic acid oxidase"
FT /id="PRO_0000035888"
FT TOPO_DOM 25..477
FT /note="Lumenal, melanosome"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT BINDING 215
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT BINDING 224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT BINDING 404
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..41
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 42..65
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 56..99
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 101..110
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 113..122
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 258..261
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 290..303
FT /evidence="ECO:0000250|UniProtKB:P17643"
SQ SEQUENCE 537 AA; 60617 MW; 2FAB599AE3FA217B CRC64;
MKSPTLLSLG YMFLVLLFFQ QAWAQFPREC ATIEALRNGV CCPDLSPLSG PGSDRCGLSS
GRGRCEVVIA DSRPHSHHYP HDGRDDREGW PTRSFNRTCH CNGNFSGHNC GTCRPGWGGA
ACDQRVLTVR RNLLDLSTEE KNRFVRALDM AKRTTHPQFV IATRRSEEIL GPDGNTPQFE
NISIYNYFVW THYYSVKKTF LGAGQESFGE VDFSHEGPAF LTWHRYHLLQ LERDMQEMLQ
DPSFSLPYWN FATGKNTCDI CTDDLMGSRS NFDSTLISPN SVFSQWRVVC ESLEDYDTLG
TLCNSTEGGP IKRNPAGNVA RPMVQRLPKP QDVAQCLEVG SYDTPPFYSN STNSFRNTVE
GYSHPTGRYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA
DISTYPLENA PIGHNRQYNM VPFWPPVTNI EMFVTAPDNL GYTYEVQWPS RSFSISEIVT
IAVVAALSLV AVIFAGASCL IRARSNMDEA NQPLLTDQYQ HYIEEYEKIH NPNQSVV
//
