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P17643 (TYRP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5,6-dihydroxyindole-2-carboxylic acid oxidase

Short name=DHICA oxidase
EC=1.14.18.-
Alternative name(s):
Catalase B
Glycoprotein 75
Melanoma antigen gp75
Tyrosinase-related protein 1
Short name=TRP
Short name=TRP-1
Short name=TRP1
Gene names
Name:TYRP1
Synonyms:CAS2, TYRP, TYRRP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length537 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. May regulate or influence the type of melanin synthesized. Ref.9

Cofactor

Binds 2 copper ions per subunit By similarity.

Pathway

Pigment biosynthesis; melanin biosynthesis.

Subcellular location

Melanosome membrane; Single-pass type I membrane protein By similarity. Note: Located to mature stage III and IV melanosomes and apposed endosomal tubular membranes. Transported to pigmented melanosomes by the BLOC-1 complex By similarity. Ref.10 Ref.11

Tissue specificity

Pigment cells.

Polymorphism

Genetic variants in TYRP1 define the skin/hair/eye pigmentation variation locus 11 (SHEP11) [MIM:612271] and are responsible for variability in hair color linked to chromosome 9p23 in Melanesians. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification.

Involvement in disease

Albinism, oculocutaneous, 3 (OCA3) [MIM:203290]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Tyrosinase activity is normal and patients have only moderate reduction of pigment. The eyes present red reflex on transillumination of the iris, dilution of color of iris, nystagmus and strabismus. Darker-skinned individuals have bright copper-red coloration of the skin and hair.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the tyrosinase family.

Ontologies

Keywords
   Biological processMelanin biosynthesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseAlbinism
Disease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCopper
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   PTMGlycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacetoacetic acid metabolic process

Inferred from electronic annotation. Source: Ensembl

melanin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

melanosome organization

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentclathrin-coated endocytic vesicle membrane

Inferred from direct assay PubMed 19841138. Source: UniProtKB

endosome membrane

Inferred from direct assay PubMed 19841138. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

melanosome

Inferred from sequence or structural similarity. Source: UniProtKB

melanosome membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncopper ion binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 19841138. Source: UniProtKB

protein heterodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GIPC1O149083EBI-7900408,EBI-373132

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 5375135,6-dihydroxyindole-2-carboxylic acid oxidase
PRO_0000035889

Regions

Topological domain25 – 477453Lumenal, melanosome Potential
Transmembrane478 – 50124Helical; Potential
Topological domain502 – 53736Cytoplasmic Potential

Sites

Metal binding1921Copper A By similarity
Metal binding2151Copper A By similarity
Metal binding2241Copper A By similarity
Metal binding3771Copper B By similarity
Metal binding3811Copper B By similarity
Metal binding4041Copper B By similarity

Amino acid modifications

Glycosylation961N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1811N-linked (GlcNAc...) Potential
Glycosylation3041N-linked (GlcNAc...) Potential
Glycosylation3501N-linked (GlcNAc...) Potential
Glycosylation3851N-linked (GlcNAc...) Potential

Natural variations

Natural variant931R → C Polymorphism associated with blond hair in individuals from the Solomon Islands; rare or absent outside of Oceania. Ref.12
VAR_068176
Natural variant3261R → H.
Corresponds to variant rs16929374 [ dbSNP | Ensembl ].
VAR_026827
Natural variant3561R → Q in OCA3. Ref.13
VAR_026828

Experimental info

Sequence conflict395 – 3962PN → SQ in CAA35820. Ref.7
Sequence conflict526 – 53712YEKLQ…NQSVV → RI Ref.1
Sequence conflict526 – 53712YEKLQ…NQSVV → RI Ref.2

Sequences

Sequence LengthMass (Da)Tools
P17643 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: 1051CEEF52908CCA

FASTA53760,724
        10         20         30         40         50         60 
MSAPKLLSLG CIFFPLLLFQ QARAQFPRQC ATVEALRSGM CCPDLSPVSG PGTDRCGSSS 

        70         80         90        100        110        120 
GRGRCEAVTA DSRPHSPQYP HDGRDDREVW PLRFFNRTCH CNGNFSGHNC GTCRPGWRGA 

       130        140        150        160        170        180 
ACDQRVLIVR RNLLDLSKEE KNHFVRALDM AKRTTHPLFV IATRRSEEIL GPDGNTPQFE 

       190        200        210        220        230        240 
NISIYNYFVW THYYSVKKTF LGVGQESFGE VDFSHEGPAF LTWHRYHLLR LEKDMQEMLQ 

       250        260        270        280        290        300 
EPSFSLPYWN FATGKNVCDI CTDDLMGSRS NFDSTLISPN SVFSQWRVVC DSLEDYDTLG 

       310        320        330        340        350        360 
TLCNSTEDGP IRRNPAGNVA RPMVQRLPEP QDVAQCLEVG LFDTPPFYSN STNSFRNTVE 

       370        380        390        400        410        420 
GYSDPTGKYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA 

       430        440        450        460        470        480 
DISTFPLENA PIGHNRQYNM VPFWPPVTNT EMFVTAPDNL GYTYEIQWPS REFSVPEIIA 

       490        500        510        520        530 
IAVVGALLLV ALIFGTASYL IRARRSMDEA NQPLLTDQYQ CYAEEYEKLQ NPNQSVV 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the cDNA encoding human tyrosinase-related protein."
Cohen T., Muller R.M., Tomita Y., Shibahara S.
Nucleic Acids Res. 18:2807-2807(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Melanoma.
[2]"Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter."
Chintamaneni C.D., Ramsay M., Colman M.-A., Fox M.F., Pickard R.T., Kwon B.S.
Biochem. Biophys. Res. Commun. 178:227-235(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein 1."
Box N.F., Wyeth J.R., Mayne C.J., O'Gorman L.E., Martin N.G., Sturm R.A.
Mamm. Genome 9:50-53(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[5]"Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family."
Sturm R.A., O'Sullivan B.J., Box N.F., Smith A.G., Smit S.E., Puttick E.R.J., Parsons P.G., Dunn I.S.
Genomics 29:24-34(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-128.
Tissue: Liver.
[6]"Downstream region of the human tyrosinase-related protein gene enhances its promoter activity."
Shibata K., Takeda K., Tomita Y., Tagami H., Shibahara S.
Biochem. Biophys. Res. Commun. 184:568-575(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
[7]"The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product."
Vijayasaradhi S., Bouchard B., Houghton A.N.
J. Exp. Med. 171:1375-1380(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 218-465, PARTIAL PROTEIN SEQUENCE.
Tissue: Melanoma.
[8]"Human tyrosinase-like protein (TYRL) carboxy terminus: closer homology with the mouse protein than previously reported."
Urquhart A.J.
Nucleic Acids Res. 19:5803-5803(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 481-537.
Tissue: Blood and Hair root.
[9]"Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity."
Halaban R., Moellmann G.
Proc. Natl. Acad. Sci. U.S.A. 87:4809-4813(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE FUNCTION.
[10]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[11]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[12]"Melanesian blond hair is caused by an amino acid change in TYRP1."
Kenny E.E., Timpson N.J., Sikora M., Yee M.C., Moreno-Estrada A., Eng C., Huntsman S., Burchard E.G., Stoneking M., Bustamante C.D., Myles S.
Science 336:554-554(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP11, VARIANT CYS-93, ASSOCIATION OF VARIANT CYS-93 WITH BLOND HAIR.
[13]"Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient."
Rooryck C., Roudaut C., Robine E., Muesebeck J., Arveiler B.
Pigment Cell Res. 19:239-242(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OCA3 GLN-356.
+Additional computationally mapped references.

Web resources

Mutations of the TYRP1 gene

Retina International's Scientific Newsletter

Albinism database (ADB)

TYRP1 mutations

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X51420 mRNA. Translation: CAA35785.1.
AF001295 Genomic DNA. Translation: AAC15468.1.
L38952 Genomic DNA. Translation: AAC41924.1.
D83059 Genomic DNA. Translation: BAA11759.1.
BC052608 mRNA. Translation: AAH52608.1.
X51455 mRNA. Translation: CAA35820.1.
X60955 Genomic DNA. Translation: CAA43288.1.
CCDSCCDS34990.1.
PIRYRHUB6. S09999.
RefSeqNP_000541.1. NM_000550.2.
UniGeneHs.270279.

3D structure databases

ProteinModelPortalP17643.
SMRP17643. Positions 129-466.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113156. 5 interactions.
IntActP17643. 1 interaction.
MINTMINT-1784675.
STRING9606.ENSP00000373570.

PTM databases

PhosphoSiteP17643.

Polymorphism databases

DMDM12644141.

Proteomic databases

PaxDbP17643.
PRIDEP17643.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000388918; ENSP00000373570; ENSG00000107165.
GeneID7306.
KEGGhsa:7306.
UCSCuc003zkv.4. human.

Organism-specific databases

CTD7306.
GeneCardsGC09P012683.
HGNCHGNC:12450. TYRP1.
HPACAB002520.
HPA000937.
MIM115501. gene.
203290. phenotype.
612271. phenotype.
neXtProtNX_P17643.
Orphanet79433. Oculocutaneous albinism type 3.
PharmGKBPA37101.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG86242.
HOGENOMHOG000118376.
HOVERGENHBG003553.
InParanoidP17643.
KOK00506.
OMAVKKTFLG.
PhylomeDBP17643.
TreeFamTF315865.

Enzyme and pathway databases

UniPathwayUPA00785.

Gene expression databases

ArrayExpressP17643.
BgeeP17643.
CleanExHS_TYRP1.
GenevestigatorP17643.

Family and domain databases

Gene3D1.10.1280.10. 1 hit.
InterProIPR015559. DiOHindole_carboxylic_A_Oxase.
IPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view]
PANTHERPTHR11474:SF3. PTHR11474:SF3. 1 hit.
PfamPF00264. Tyrosinase. 1 hit.
[Graphical view]
PRINTSPR00092. TYROSINASE.
SUPFAMSSF48056. SSF48056. 2 hits.
PROSITEPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTYRP1.
GenomeRNAi7306.
NextBio28568.
PROP17643.
SOURCESearch...

Entry information

Entry nameTYRP1_HUMAN
AccessionPrimary (citable) accession number: P17643
Secondary accession number(s): P78468 expand/collapse secondary AC list , P78469, Q13721, Q15679
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 11, 2001
Last modified: July 9, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM