P40126 (TYRP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
L-dopachrome tautomerase
Short name=DCT
Short name=DT
EC=5.3.3.12

Alternative name(s):
L-dopachrome Delta-isomerase
Tyrosinase-related protein 2
Short name=TRP-2
Short name=TRP2

Gene names

Name:	DCT
Synonyms:	TYRP2

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	519 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	Involved in regulating eumelanin and phaeomelanin levels.
Catalytic activity	L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.
Cofactor	Binds 2 zinc ions per subunit By similarity.
Pathway	Pigment biosynthesis; melanin biosynthesis.
Subunit structure	Tyrosinase, TYRP1 and DCT/TYRP2 may form a multienzyme complex By similarity.
Subcellular location	Melanosome membrane; Single-pass type I membrane protein Ref.8 Ref.9.
Sequence similarities	Belongs to the tyrosinase family.

Ontologies

Keywords
Biological process	Melanin biosynthesis
Cellular component	Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Isomerase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	epidermis development Traceable author statement. Source: ProtInc melanin biosynthetic process from tyrosine Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Traceable author statement. Source: ProtInc melanosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	copper ion binding Traceable author statement. Source: ProtInc dopachrome isomerase activity Inferred from sequence or structural similarity. Source: UniProtKB oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 519	496	L-dopachrome tautomerase		PRO_0000035892
Regions
	Topological domain	24 – 472	449	Lumenal, melanosome Potential
	Transmembrane	473 – 493	21	Helical; Potential
	Topological domain	494 – 519	26	Cytoplasmic Potential
Sites
	Metal binding	189	1	Zinc A By similarity
	Metal binding	211	1	Zinc A By similarity
	Metal binding	220	1	Zinc A By similarity
	Metal binding	369	1	Zinc B By similarity
	Metal binding	373	1	Zinc B By similarity
	Metal binding	396	1	Zinc B By similarity
Amino acid modifications
	Glycosylation	170	1	N-linked (GlcNAc...) Potential
	Glycosylation	178	1	N-linked (GlcNAc...) Potential
	Glycosylation	237	1	N-linked (GlcNAc...) Potential
	Glycosylation	300	1	N-linked (GlcNAc...) Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	377	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P40126 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: AFDDF21768002A89	FASTA	519	59,145
	10 20 30 40 50 60 MSPLWWGFLL SCLGCKILPG AQGQFPRVCM TVDSLVNKEC CPRLGAESAN VCGSQQGRGQ 70 80 90 100 110 120 CTEVRADTRP WSGPYILRNQ DDRELWPRKF FHRTCKCTGN FAGYNCGDCK FGWTGPNCER 130 140 150 160 170 180 KKPPVIRQNI HSLSPQEREQ FLGALDLAKK RVHPDYVITT QHWLGLLGPN GTQPQFANCS 190 200 210 220 230 240 VYDFFVWLHY YSVRDTLLGP GRPYRAIDFS HQGPAFVTWH RYHLLCLERD LQRLIGNESF 250 260 270 280 290 300 ALPYWNFATG RNECDVCTDQ LFGAARPDDP TLISRNSRFS SWETVCDSLD DYNHLVTLCN 310 320 330 340 350 360 GTYEGLLRRN QMGRNSMKLP TLKDIRDCLS LQKFDNPPFF QNSTFSFRNA LEGFDKADGT 370 380 390 400 410 420 LDSQVMSLHN LVHSFLNGTN ALPHSAANDP IFVVLHSFTD AIFDEWMKRF NPPADAWPQE 430 440 450 460 470 480 LAPIGHNRMY NMVPFFPPVT NEELFLTSDQ LGYSYAIDLP VSVEETPGWP TTLLVVMGTL 490 500 510 VALVGLFVLL AFLQYRRLRK GYTPLMETHL SSKRYTEEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional analysis of a cDNA coding for human DOPAchrome tautomerase/tyrosinase-related protein-2." Yokoyama K., Suzuki H., Yasumoto K.I., Tomita Y., Shibahara S. Biochim. Biophys. Acta 1217:317-321(1994) [PubMed: 8148378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA." Cassady J.L., Sturm R.A. Gene 143:295-298(1994) [PubMed: 8206391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns of expression in melanocytic cells." Bouchard B., del Marmol V., Jackson I.J., Cherif D., Dubertret L. Eur. J. Biochem. 219:127-134(1994) [PubMed: 8306979] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Mammary gland.
[6]	"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 1-98. Tissue: Liver.
[7]	"Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression." Yokoyama K., Yasumoto K.I., Suzuki H., Shibahara S. J. Biol. Chem. 269:27080-27087(1994) [PubMed: 7929451] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98. Tissue: Liver.
[8]	"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.
[9]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D17547 mRNA. Translation: BAA04484.1. L18967 mRNA. Translation: AAA20870.1. S69231 mRNA. Translation: AAC60627.1. AL139318 Genomic DNA. Translation: CAC19460.1. BC028311 mRNA. Translation: AAH28311.1. L38953 Genomic DNA. Translation: AAC41925.1. D28767 Genomic DNA. Translation: BAA05956.1.
IPI	IPI00027343.
PIR	YRHUR2. S43510.
RefSeq	NP_001913.2. NM_001922.3.
UniGene	Hs.301865.
3D structure databases
ProteinModelPortal	P40126.
SMR	P40126. Positions 124-457.
ModBase	Search...
Protein-protein interaction databases
STRING	P40126.
PTM databases
PhosphoSite	P40126.
Polymorphism databases
DMDM	731026.
Proteomic databases
PRIDE	P40126.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377028; ENSP00000366227; ENSG00000080166.
GeneID	1638.
KEGG	hsa:1638.
UCSC	uc001vlv.2. human.
Organism-specific databases
CTD	1638.
GeneCards	GC13M095091.
H-InvDB	HIX0011400.
HGNC	HGNC:2709. DCT.
HPA	CAB017634. HPA010743. HPA010800.
MIM	191275. gene.
neXtProt	NX_P40126.
PharmGKB	PA27179.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG003553.
InParanoid	P40126.
PhylomeDB	P40126.
Gene expression databases
ArrayExpress	P40126.
Bgee	P40126.
CleanEx	HS_DCT.
Genevestigator	P40126.
GermOnline	ENSG00000080166. Homo sapiens.
Family and domain databases
InterPro	IPR002227. Tyrosinase. IPR008922. Unchr_di-copper_centre. [Graphical view]
Gene3D	G3DSA:1.10.1280.10. Di-copper_centre. 1 hit.
KO	K01827.
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	6730.
SOURCE	Search...

Entry information

Entry name

TYRP2_HUMAN

Accession

Primary (citable) accession number: P40126

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 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.