P17643 (TYRP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	537 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 Probable Ref.10 Ref.11.
Tissue specificity	Pigment cells.
Involvement in disease	Defects in TYRP1 are the cause of albinism oculocutaneous type 3 (OCA3) [MIM:203290]; also known as Rufous oculocutaneous albinism. 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. Ref.12
Sequence similarities	Belongs to the tyrosinase family.

Ontologies

Keywords
Biological process	Melanin biosynthesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Albinism Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Ligand	Copper Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	melanin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	clathrin-coated endocytic vesicle membrane Inferred from direct assay. Source: UniProtKB endosome membrane Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW melanosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	copper 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 heterodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24
	Chain	25 – 537	513	5,6-dihydroxyindole-2-carboxylic acid oxidase		PRO_0000035889
Regions
	Topological domain	25 – 477	453	Lumenal, melanosome Potential
	Transmembrane	478 – 501	24	Helical; Potential
	Topological domain	502 – 537	36	Cytoplasmic Potential
Sites
	Metal binding	192	1	Copper A By similarity
	Metal binding	215	1	Copper A By similarity
	Metal binding	224	1	Copper A By similarity
	Metal binding	377	1	Copper B By similarity
	Metal binding	381	1	Copper B By similarity
	Metal binding	404	1	Copper B By similarity
Amino acid modifications
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	304	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	385	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	326	1	R → H. Corresponds to variant rs16929374 [ dbSNP | Ensembl ].		VAR_026827
	Natural variant	356	1	R → Q in OCA3. Ref.12		VAR_026828
Experimental info
	Sequence conflict	395 – 396	2	PN → SQ in CAA35820. Ref.7
	Sequence conflict	526 – 537	12	YEKLQ…NQSVV → RI Ref.1
	Sequence conflict	526 – 537	12	YEKLQ…NQSVV → RI Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P17643 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 1051CEEF52908CCA	FASTA	537	60,724
	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

References

	« Hide 'large scale' referencesShow '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: 2111010] [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: 1906272] [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: 9434945] [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: 15489334] [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: 8530077] [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: 1575733] [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: 2324688] [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: 1945866] [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: 1693779] [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: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. 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: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[12]	"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: 16704458] [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.
IPI	IPI00015913.
PIR	YRHUB6. S09999.
RefSeq	NP_000541.1. NM_000550.2.
UniGene	Hs.270279.
3D structure databases
ProteinModelPortal	P17643.
SMR	P17643. Positions 126-466.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1784675.
STRING	P17643.
PTM databases
PhosphoSite	P17643.
Polymorphism databases
DMDM	12644141.
Proteomic databases
PRIDE	P17643.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000388918; ENSP00000373570; ENSG00000107165.
GeneID	7306.
KEGG	hsa:7306.
UCSC	uc003zkv.2. human.
Organism-specific databases
CTD	7306.
GeneCards	GC09P012683.
H-InvDB	HIX0025869.
HGNC	HGNC:12450. TYRP1.
HPA	CAB002520. HPA000937.
MIM	115501. gene. 203290. phenotype.
neXtProt	NX_P17643.
Orphanet	79433. Oculocutaneous albinism type 3.
PharmGKB	PA37101.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13118.
HOGENOM	HBG447182.
HOVERGEN	HBG003553.
InParanoid	P17643.
OMA	HYYSVKK.
Gene expression databases
ArrayExpress	P17643.
Bgee	P17643.
CleanEx	HS_TYRP1.
Genevestigator	P17643.
GermOnline	ENSG00000107165. Homo sapiens.
Family and domain databases
InterPro	IPR015559. DiOHindole_carboxylic_A_Oxase. IPR002227. Tyrosinase. IPR008922. Unchr_di-copper_centre. [Graphical view]
Gene3D	G3DSA:1.10.1280.10. Di-copper_centre. 1 hit.
KO	K00506.
PANTHER	PTHR11474:SF3. DHXI_oxidase. 1 hit.
Pfam	PF00264. Tyrosinase. 1 hit. [Graphical view]
PRINTS	PR00092. TYROSINASE.
SUPFAM	SSF48056. Di-copper_centre. 1 hit.
PROSITE	PS00497. TYROSINASE_1. 1 hit. PS00498. TYROSINASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	28568.
SOURCE	Search...

Entry information

Entry name

TYRP1_HUMAN

Accession

Primary (citable) accession number: P17643
Secondary accession number(s): P78468 , P78469, Q13721, Q15679

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 11, 2001
Last modified:	December 14, 2011
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.