TYRP1_AMBME
ID TYRP1_AMBME Reviewed; 534 AA.
AC P55027;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 94.
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 Ambystoma mexicanum (Axolotl).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Ambystomatidae; Ambystoma.
OX NCBI_TaxID=8296;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mason K.A., Moody M., Amack J., Thibaudeau G.;
RT "Complete cDNA for Ambystoma mexicanum TRP-1.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-436.
RX PubMed=7792254; DOI=10.1111/j.1600-0749.1995.tb00773.x;
RA Mason K.A., Mason S.K.;
RT "The identification and partial cloning by PCR of the gene for tyrosinase-
RT related protein-1 in the Mexican axolotl.";
RL Pigment Cell Res. 8:46-52(1995).
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 -!- 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 -!- SUBCELLULAR LOCATION: Melanosome membrane
CC {ECO:0000250|UniProtKB:P07147}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P07147}. Melanosome
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 -!- 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; AF064803; AAC17168.1; -; mRNA.
DR PIR; I51282; I51282.
DR AlphaFoldDB; P55027; -.
DR SMR; P55027; -.
DR UniPathway; UPA00785; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1280.10; -; 1.
DR InterPro; IPR008922; Di-copper_centre_dom_sf.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR002227; Tyrosinase_Cu-bd.
DR Pfam; PF00053; Laminin_EGF; 1.
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 2: Evidence at transcript level;
KW Copper; Disulfide bond; Glycoprotein; Melanin biosynthesis; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..534
FT /note="5,6-dihydroxyindole-2-carboxylic acid oxidase"
FT /id="PRO_0000035886"
FT TOPO_DOM 24..477
FT /note="Lumenal, melanosome"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..534
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 175
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 29..40
FT /evidence="ECO:0000250|UniProtKB:P17643"
FT DISULFID 41..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 534 AA; 59609 MW; 40EB807CB5F36093 CRC64;
MLGPATFLPL TAALLLLIPG GRAQFPRQCV TPEALRSGQC CPGLFPALTP DPADRCGASV
GRGRCAPLQV DARPHGPQYP HDGVDDREQW PTRFFNNSCL CAENFSGYDC GSCKPGWVGV
NCNQRVLAVR RNILDLTAQE RRRFIAALDL AKRTTHPHYV IASRRYAEIM GPDGNSTQFE
NVSIYNFFVW THYYSIGKTF LGAGRESFGG IDFSHEGPAF VTWHRYHLLQ LERDMQEMLQ
DPTFALPYWN FAIGGNECDI CTDDFMGARS NFDSILLSSN SVFSQWRVLC ESLEGYDTLG
TICNSTEGGP IRRNPGGNVA RPMVQRLPEP QDVALCLEVG LFDTPPFYSN SSESFRNTVE
GYSEPSGKYD PSVRSLHNLA HLFLNGTGGQ THVSPNDPIF VLLHTFTDAV FDEWLRRHNA
DISLYPLENA PIGHNRQYNM VPFWPPVSNN EMFVTAPESL GYSYEVQWPS RALNFTEIIT
IAVVAALVLV AVIFAAASCA VHRSRKDDVH QPLLGEQYPR YSEEYERDAS QSAV
