TYRP1_MOUSE
ID TYRP1_MOUSE Reviewed; 537 AA.
AC P07147;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=5,6-dihydroxyindole-2-carboxylic acid oxidase;
DE Short=DHICA oxidase {ECO:0000303|PubMed:7813420};
DE EC=1.14.18.- {ECO:0000269|PubMed:7813420};
DE AltName: Full=Brown locus protein;
DE AltName: Full=Catalase B;
DE AltName: Full=Tyrosinase-related protein 1;
DE Short=TRP;
DE Short=TRP-1;
DE Short=TRP1;
DE Flags: Precursor;
GN Name=Tyrp1; Synonyms=Tyrp-1;
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 TISSUE=Melanoma;
RX PubMed=3008090; DOI=10.1093/nar/14.6.2413;
RA Shibahara S., Tomita Y., Sakakura T., Nager C., Chaudhuri B., Mueller R.;
RT "Cloning and expression of cDNA encoding mouse tyrosinase.";
RL Nucleic Acids Res. 14:2413-2427(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION OF PROTEIN.
RX PubMed=3132713; DOI=10.1073/pnas.85.12.4392;
RA Jackson I.J.;
RT "A cDNA encoding tyrosinase-related protein maps to the brown locus in
RT mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:4392-4396(1988).
RN [4]
RP POSSIBLE FUNCTION.
RX PubMed=1693779; DOI=10.1073/pnas.87.12.4809;
RA Halaban R., Moellmann G.;
RT "Murine and human b locus pigmentation genes encode a glycoprotein (gp75)
RT with catalase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4809-4813(1990).
RN [5]
RP FUNCTION, 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 [6]
RP POSSIBLE FUNCTION.
RX PubMed=8270621; DOI=10.1242/jcs.106.1.153;
RA Winder A.J., Wittbjer A., Rosengren E., Rorsman H.;
RT "The mouse brown (b) locus protein has dopachrome tautomerase activity and
RT is located in lysosomes in transfected fibroblasts.";
RL J. Cell Sci. 106:153-166(1993).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7813420; DOI=10.1002/j.1460-2075.1994.tb06925.x;
RA Kobayashi T., Urabe K., Winder A., Jimenez-Cervantes C., Imokawa G.,
RA Brewington T., Solano F., Garcia-Borron J.C., Hearing V.J.;
RT "Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in
RT melanin biosynthesis.";
RL EMBO J. 13:5818-5825(1994).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=17182842; DOI=10.1091/mbc.e06-12-1066;
RA Setty S.R., Tenza D., Truschel S.T., Chou E., Sviderskaya E.V., Theos A.C.,
RA Lamoreux M.L., Di Pietro S.M., Starcevic M., Bennett D.C.,
RA Dell'Angelica E.C., Raposo G., Marks M.S.;
RT "BLOC-1 is required for cargo-specific sorting from vacuolar early
RT endosomes toward lysosome-related organelles.";
RL Mol. Biol. Cell 18:768-780(2007).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ATP7A.
RX PubMed=18650808; DOI=10.1038/nature07163;
RA Setty S.R., Tenza D., Sviderskaya E.V., Bennett D.C., Raposo G.,
RA Marks M.S.;
RT "Cell-specific ATP7A transport sustains copper-dependent tyrosinase
RT activity in melanosomes.";
RL Nature 454:1142-1146(2008).
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 VARIANTS BROWN TYR-110 AND HIS-326, FUNCTION, AND PATHWAY.
RX PubMed=2245916; DOI=10.1093/genetics/126.2.443;
RA Zdarsky E., Favor J., Jackson I.J.;
RT "The molecular basis of brown, an old mouse mutation, and of an induced
RT revertant to wild type.";
RL Genetics 126:443-449(1990).
CC -!- FUNCTION: Plays a role in melanin biosynthesis (PubMed:2245916).
CC Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid
CC (DHICA) into indole-5,6-quinone-2-carboxylic acid (PubMed:7813420). May
CC regulate or influence the type of melanin synthesized (PubMed:7813420,
CC PubMed:2245916). Also to a lower extent, capable of hydroxylating
CC tyrosine and producing melanin (PubMed:1537333).
CC {ECO:0000269|PubMed:1537333, ECO:0000269|PubMed:2245916,
CC ECO:0000269|PubMed:7813420}.
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:0000269|PubMed:2245916}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with ATP7A
CC (PubMed:18650808). {ECO:0000250|UniProtKB:P17643,
CC ECO:0000269|PubMed:18650808}.
CC -!- INTERACTION:
CC P07147; P11344: Tyr; NbExp=8; IntAct=EBI-821614, EBI-821603;
CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:17182842,
CC ECO:0000269|PubMed:18650808}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:17182842}. Melanosome
CC {ECO:0000269|PubMed:26620560}. 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:0000269|PubMed:17182842, ECO:0000269|PubMed:26620560}.
CC -!- TISSUE SPECIFICITY: Pigment cells.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:1537333}.
CC -!- DISEASE: Note=Defects in Tyrp1 are the cause of the brown (b)
CC phenotype. Brown mice have a brown or hypopigmented coat.
CC {ECO:0000269|PubMed:2245916}.
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
CC (PubMed:7813420). 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:P17643, ECO:0000269|PubMed:7813420,
CC ECO:0000305}.
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DR EMBL; X03687; CAA27323.1; -; mRNA.
DR EMBL; BC076598; AAH76598.1; -; mRNA.
DR CCDS; CCDS18290.1; -.
DR PIR; A24933; YRMSB6.
DR RefSeq; NP_001268943.1; NM_001282014.1.
DR RefSeq; NP_001268944.1; NM_001282015.1.
DR RefSeq; NP_112479.1; NM_031202.3.
DR PDB; 6MP0; X-ray; 2.00 A; A=455-463.
DR PDB; 6MP1; X-ray; 2.21 A; A=455-463.
DR PDBsum; 6MP0; -.
DR PDBsum; 6MP1; -.
DR AlphaFoldDB; P07147; -.
DR SMR; P07147; -.
DR IntAct; P07147; 1.
DR STRING; 10090.ENSMUSP00000006151; -.
DR BindingDB; P07147; -.
DR ChEMBL; CHEMBL3638355; -.
DR GlyGen; P07147; 6 sites.
DR iPTMnet; P07147; -.
DR PhosphoSitePlus; P07147; -.
DR PaxDb; P07147; -.
DR PRIDE; P07147; -.
DR ProteomicsDB; 297764; -.
DR Antibodypedia; 745; 742 antibodies from 32 providers.
DR DNASU; 22178; -.
DR Ensembl; ENSMUST00000006151; ENSMUSP00000006151; ENSMUSG00000005994.
DR Ensembl; ENSMUST00000102831; ENSMUSP00000099895; ENSMUSG00000005994.
DR GeneID; 22178; -.
DR KEGG; mmu:22178; -.
DR UCSC; uc008tjq.3; mouse.
DR CTD; 7306; -.
DR MGI; MGI:98881; Tyrp1.
DR VEuPathDB; HostDB:ENSMUSG00000005994; -.
DR eggNOG; ENOG502QRNA; Eukaryota.
DR GeneTree; ENSGT00940000155804; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR InParanoid; P07147; -.
DR OMA; ATRHYSD; -.
DR OrthoDB; 518234at2759; -.
DR PhylomeDB; P07147; -.
DR TreeFam; TF315865; -.
DR BioCyc; MetaCyc:MON-15620; -.
DR Reactome; R-MMU-5662702; Melanin biosynthesis.
DR UniPathway; UPA00785; -.
DR BioGRID-ORCS; 22178; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tyrp1; mouse.
DR PRO; PR:P07147; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P07147; protein.
DR Bgee; ENSMUSG00000005994; Expressed in iris and 62 other tissues.
DR ExpressionAtlas; P07147; baseline and differential.
DR Genevisible; P07147; MM.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0097708; C:intracellular vesicle; ISO:MGI.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004503; F:tyrosinase activity; ISS:UniProtKB.
DR GO; GO:0043438; P:acetoacetic acid metabolic process; IMP:MGI.
DR GO; GO:0006583; P:melanin biosynthetic process from tyrosine; TAS:UniProtKB.
DR GO; GO:0006582; P:melanin metabolic process; IMP:MGI.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI.
DR GO; GO:0032438; P:melanosome organization; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:MGI.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IGI:CACAO.
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 3D-structure; Albinism; Copper; Disease variant; Disulfide bond;
KW Glycoprotein; Melanin biosynthesis; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1..24
FT CHAIN 25..537
FT /note="5,6-dihydroxyindole-2-carboxylic acid oxidase"
FT /id="PRO_0000035890"
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"
FT VARIANT 110
FT /note="C -> Y (in brown)"
FT /evidence="ECO:0000269|PubMed:2245916"
FT VARIANT 326
FT /note="R -> H (in brown)"
FT /evidence="ECO:0000269|PubMed:2245916"
SQ SEQUENCE 537 AA; 60761 MW; 86570998AA9EB0BC CRC64;
MKSYNVLPLA YISLFLMLFY QVWAQFPREC ANIEALRRGV CCPDLLPSSG PGTDPCGSSS
GRGRCVAVIA DSRPHSRHYP HDGKDDREAW PLRFFNRTCQ CNDNFSGHNC GTCRPGWRGA
ACNQKILTVR RNLLDLSPEE KSHFVRALDM AKRTTHPQFV IATRRLEDIL GPDGNTPQFE
NISVYNYFVW THYYSVKKTF LGTGQESFGD VDFSHEGPAF LTWHRYHLLQ LERDMQEMLQ
EPSFSLPYWN FATGKNVCDV CTDDLMGSRS NFDSTLISPN SVFSQWRVVC ESLEEYDTLG
TLCNSTEGGP IRRNPAGNVG RPAVQRLPEP QDVTQCLEVR VFDTPPFYSN STDSFRNTVE
GYSAPTGKYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA
DISTFPLENA PIGHNRQYNM VPFWPPVTNT EMFVTAPDNL GYAYEVQWPG QEFTVSEIIT
IAVVAALLLV AAIFGVASCL IRSRSTKNEA NQPLLTDHYQ RYAEDYEELP NPNHSMV
