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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.9 Ref.10.
Sequence similarities	Belongs to the tyrosinase family.

Ontologies

Keywords
Biological process	Melanin biosynthesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
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	cell development Inferred from electronic annotation. Source: Compara developmental pigmentation Inferred from electronic annotation. Source: Compara epidermis development Traceable author statement Ref.2. Source: ProtInc melanin biosynthetic process from tyrosine Inferred from sequence or structural similarity. Source: UniProtKB oxidation-reduction process Inferred from electronic annotation. Source: GOC positive regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara ventricular zone neuroblast division Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Traceable author statement Ref.2. Source: ProtInc melanosome Inferred from sequence or structural similarity. Source: UniProtKB melanosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	copper ion binding Traceable author statement Ref.2. Source: ProtInc dopachrome isomerase activity Inferred from sequence or structural similarity. Source: UniProtKB oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P40126-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P40126-2)

Also known as: TRP-2-6b;

The sequence of this isoform differs from the canonical sequence as follows:
     393-393: V → VVISNRLLYNATTNILEHVRKEKATKELPSLHVL

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
Natural variations
	Alternative sequence	393	1	V → VVISNRLLYNATTNILEHVR KEKATKELPSLHVL in isoform 2.		VSP_043581

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2 (TRP-2-6b) [UniParc]. Checksum: F2B047A524167DD3	FASTA	552	62,929
	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 IFVVISNRLL YNATTNILEH VRKEKATKEL 430 440 450 460 470 480 PSLHVLVLHS FTDAIFDEWM KRFNPPADAW PQELAPIGHN RMYNMVPFFP PVTNEELFLT 490 500 510 520 530 540 SDQLGYSYAI DLPVSVEETP GWPTTLLVVM GTLVALVGLF VLLAFLQYRR LRKGYTPLME 550 THLSSKRYTE EA

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA." Cassady J.L., Sturm R.A. Gene 143:295-298(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Pre-existing immunity to tyrosinase-related protein (TRP)-2, a new TRP-2 isoform, and the NY-ESO-1 melanoma antigen in a patient with a dramatic response to immunotherapy." Khong H.T., Rosenberg S.A. J. Immunol. 168:951-956(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING. Tissue: Melanoma.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Mammary gland.
[7]	"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 1-98. Tissue: Liver.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98. Tissue: Liver.
[9]	"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], MASS SPECTROMETRY. Tissue: Melanoma.
[10]	"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], 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. DQ902581 mRNA. Translation: ABI73976.1. 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. IPI00798153.
PIR	YRHUR2. S43510.
RefSeq	NP_001123361.1. NM_001129889.1. NP_001913.2. NM_001922.3.
UniGene	Hs.301865.
3D structure databases
ProteinModelPortal	P40126.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000392762.
PTM databases
PhosphoSite	P40126.
Polymorphism databases
DMDM	731026.
Proteomic databases
PaxDb	P40126.
PRIDE	P40126.
Protocols and materials databases
DNASU	1638.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377028; ENSP00000366227; ENSG00000080166. ENST00000446125; ENSP00000392762; ENSG00000080166.
GeneID	1638.
KEGG	hsa:1638.
UCSC	uc001vlv.4. human.
Organism-specific databases
CTD	1638.
GeneCards	GC13M095091.
HGNC	HGNC:2709. DCT.
HPA	CAB017634. HPA010743. HPA010800.
MIM	191275. gene.
neXtProt	NX_P40126.
PharmGKB	PA27179.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG301916.
HOGENOM	HOG000118376.
HOVERGEN	HBG003553.
InParanoid	P40126.
KO	K01827.
OMA	WPRKFFN.
PhylomeDB	P40126.
Enzyme and pathway databases
UniPathway	UPA00785.
Gene expression databases
ArrayExpress	P40126.
Bgee	P40126.
CleanEx	HS_DCT.
Genevestigator	P40126.
GermOnline	ENSG00000080166. Homo sapiens.
Family and domain databases
Gene3D	1.10.1280.10. 1 hit.
InterPro	IPR002227. Tyrosinase. IPR008922. Unchr_di-copper_centre. [Graphical view]
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
GenomeRNAi	1638.
NextBio	6730.
SOURCE	Search...

Entry information

Entry name

TYRP2_HUMAN

Accession

Primary (citable) accession number: P40126
Secondary accession number(s): Q09GT4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 126 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.