TYRP1_FELCA
ID TYRP1_FELCA Reviewed; 537 AA.
AC Q2VPW6; Q2VPU6; Q2VPU7; Q2VPU8; Q4VNX7; Q4VNX8;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 71.
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;
DE Short=TRP-1;
DE Short=TRP1;
DE Flags: Precursor;
GN Name=TYRP1;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS GLY-3;
RP TYR-19; SER-28; VAL-31; ALA-44 AND 100-ARG--VAL-537 DEL.
RX PubMed=15858157; DOI=10.1093/jhered/esi066;
RA Schmidt-Kuntzel A., Eizirik E., O'Brien S.J., Menotti-Raymond M.;
RT "Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat
RT coat color phenotypes of the albino and brown loci.";
RL J. Hered. 96:289-301(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-3 AND VAL-31.
RX PubMed=16104383; DOI=10.1007/s00335-004-2455-4;
RA Lyons L.A., Foe I.T., Rah H.C., Grahn R.A.;
RT "Chocolate coated cats: TYRP1 mutations for brown color in domestic cats.";
RL Mamm. Genome 16:356-366(2005).
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 in the presence of bound Cu(2+) ions, but not
CC in the presence of Zn(2+). May regulate or influence the type of
CC melanin synthesized (By similarity). Also to a lower extent, capable of
CC hydroxylating tyrosine and producing melanin (By similarity).
CC {ECO:0000250|UniProtKB:P07147, 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, giving rise to a protein that lacks DHICA oxidase activity.
CC {ECO:0000250|UniProtKB:P17643};
CC -!- ACTIVITY REGULATION: The activity depends critically on the nature of
CC the bound metal ion. Catalyzes the oxidation of 5,6-dihydroxyindole-2-
CC carboxylic acid (DHICA) in the presence of bound Cu(2+) ions, but lacks
CC activity in the presence of bound Zn(2+) ions.
CC {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 {ECO:0000250|UniProtKB:P07147, 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q2VPW6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2VPW6-2; Sequence=VSP_060953;
CC Name=3;
CC IsoId=Q2VPW6-3; Sequence=VSP_060954;
CC -!- POLYMORPHISM: Allelic variations in TYRP1 may be associated with brown
CC (allele chocolate) or cinnamon (allele cinnamon) coat color in domestic
CC cats. {ECO:0000269|PubMed:15858157, ECO:0000269|PubMed:16104383}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to competing donor splice site.
CC {ECO:0000269|PubMed:15858157}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to competing donor splice site.
CC {ECO:0000269|PubMed:15858157}.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
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DR EMBL; AY956310; AAY29636.1; -; mRNA.
DR EMBL; AY965743; AAY87040.1; -; mRNA.
DR EMBL; AY965744; AAY87041.1; -; mRNA.
DR EMBL; AY965745; AAY87042.1; -; mRNA.
DR EMBL; AH014499; AAV65117.1; -; Genomic_DNA.
DR EMBL; AY804220; AAV65117.1; JOINED; Genomic_DNA.
DR EMBL; AY804221; AAV65117.1; JOINED; Genomic_DNA.
DR EMBL; AY804222; AAV65117.1; JOINED; Genomic_DNA.
DR EMBL; AY804223; AAV65117.1; JOINED; Genomic_DNA.
DR EMBL; AY804224; AAV65117.1; JOINED; Genomic_DNA.
DR EMBL; AH014501; AAV65119.1; -; Genomic_DNA.
DR EMBL; AY804235; AAV65119.1; JOINED; Genomic_DNA.
DR EMBL; AY804236; AAV65119.1; JOINED; Genomic_DNA.
DR EMBL; AY804237; AAV65119.1; JOINED; Genomic_DNA.
DR EMBL; AY804239; AAV65119.1; JOINED; Genomic_DNA.
DR EMBL; AY804240; AAV65119.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001036025.2; NM_001042560.2. [Q2VPW6-1]
DR AlphaFoldDB; Q2VPW6; -.
DR SMR; Q2VPW6; -.
DR GeneID; 554339; -.
DR KEGG; fca:554339; -.
DR CTD; 7306; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR OrthoDB; 518234at2759; -.
DR UniPathway; UPA00785; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
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; 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 2: Evidence at transcript level;
KW Alternative splicing; Copper; Disulfide bond; Glycoprotein;
KW Melanin biosynthesis; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..537
FT /note="5,6-dihydroxyindole-2-carboxylic acid oxidase"
FT /evidence="ECO:0000255"
FT /id="PRO_5004217942"
FT TOPO_DOM 25..480
FT /note="Lumenal, melanosome"
FT /evidence="ECO:0000305"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
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 CARBOHYD 472
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 VAR_SEQ 420
FT /note="A -> AGETFSYAFLRAQQGDRS (in isoform 2)"
FT /id="VSP_060953"
FT VAR_SEQ 420
FT /note="A -> AGETFSYAFLRAQQGDRSG (in isoform 3)"
FT /id="VSP_060954"
FT VARIANT 3
FT /note="A -> G (may be associated with brown coat color
FT phenotype)"
FT /evidence="ECO:0000269|PubMed:15858157,
FT ECO:0000269|PubMed:16104383"
FT VARIANT 19
FT /note="S -> Y"
FT /evidence="ECO:0000269|PubMed:15858157"
FT VARIANT 28
FT /note="R -> S"
FT /evidence="ECO:0000269|PubMed:15858157"
FT VARIANT 31
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:15858157,
FT ECO:0000269|PubMed:16104383"
FT VARIANT 44
FT /note="D -> A"
FT /evidence="ECO:0000269|PubMed:15858157"
FT VARIANT 100..537
FT /note="Missing (might be associated with cinnamon coat
FT color phenotype)"
FT /evidence="ECO:0000269|PubMed:15858157"
FT CONFLICT 155
FT /note="M -> I (in Ref. 2; AAV65117/AAV65119)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="N -> K (in Ref. 2; AAV65117/AAV65119)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 60636 MW; EEC8BDC598F38E23 CRC64;
MKAHKFLSLG YIVLPLLCSP QTWAQFPRQC ATVEALRNGV CCPDLSPLSG PGTDRCGSSS
GRGRCEAVTA DSRPHSLHYP HDGRDDREAW PTRFFNRTCR CNGNFSGHNC GTCRPGWKGA
ACDQRVLIVR RNLLDLSAEE KNHLVQALHL AKRTMHPQFV IATRRSEEIL GPDGNTPQFE
NISIYNYFVW THYYSVKKTF LGPGQESFGE VDFSHEGPAF LTWHRYHLLQ LERDMQEMLQ
DPSFSLPYWN FATGKNICDI CTDDLMGSRS NFDPTLISLN SVFSQWRVVC ESLEDYDTLG
TLCNSTEGGP IRRNPAGNVA RPMVQRLPEP QDVAQCLEVG LFDTPPFYSN STNSFRNTVE
GYSDPTGKYD PAIRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA
DVSTFPLENA PIGHNRQYNM VPFWPPVTNI EMFVTAPDNL GYTYEVQWPS RNFSISELVT
IGVVAALSLV AVIFAGASCM IRARSNMDEA HQPLLTDQYQ HYAEEYEKMH NPNQSMV
