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P40126 (TYRP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length519 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processMelanin biosynthesis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionIsomerase
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell development

Inferred from electronic annotation. Source: Ensembl

developmental pigmentation

Inferred from electronic annotation. Source: Ensembl

epidermis development

Traceable author statement Ref.2. Source: ProtInc

melanin biosynthetic process from tyrosine

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

ventricular zone neuroblast division

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of 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_functioncopper 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 519496L-dopachrome tautomerase
PRO_0000035892

Regions

Topological domain24 – 472449Lumenal, melanosome Potential
Transmembrane473 – 49321Helical; Potential
Topological domain494 – 51926Cytoplasmic Potential

Sites

Metal binding1891Zinc A By similarity
Metal binding2111Zinc A By similarity
Metal binding2201Zinc A By similarity
Metal binding3691Zinc B By similarity
Metal binding3731Zinc B By similarity
Metal binding3961Zinc B By similarity

Amino acid modifications

Glycosylation1701N-linked (GlcNAc...) Potential
Glycosylation1781N-linked (GlcNAc...) Potential
Glycosylation2371N-linked (GlcNAc...) Potential
Glycosylation3001N-linked (GlcNAc...) Potential
Glycosylation3421N-linked (GlcNAc...) Potential
Glycosylation3771N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence3931V → VVISNRLLYNATTNILEHVR KEKATKELPSLHVL in isoform 2.
VSP_043581

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: AFDDF21768002A89

FASTA51959,145
        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 

« Hide

Isoform 2 (TRP-2-6b) [UniParc].

Checksum: F2B047A524167DD3
Show »

FASTA55262,929

References

« Hide '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. expand/collapse author list , 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].
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].
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.
CCDSCCDS45060.1. [P40126-2]
CCDS9470.1. [P40126-1]
PIRYRHUR2. S43510.
RefSeqNP_001123361.1. NM_001129889.1. [P40126-2]
NP_001913.2. NM_001922.3. [P40126-1]
UniGeneHs.301865.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4HX1X-ray1.80C180-188[»]
ProteinModelPortalP40126.
SMRP40126. Positions 210-459.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108006. 1 interaction.
STRING9606.ENSP00000392762.

PTM databases

PhosphoSiteP40126.

Polymorphism databases

DMDM731026.

Proteomic databases

PaxDbP40126.
PRIDEP40126.

Protocols and materials databases

DNASU1638.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377028; ENSP00000366227; ENSG00000080166. [P40126-1]
ENST00000446125; ENSP00000392762; ENSG00000080166. [P40126-2]
GeneID1638.
KEGGhsa:1638.
UCSCuc001vlv.4. human. [P40126-1]
uc010afh.3. human. [P40126-2]

Organism-specific databases

CTD1638.
GeneCardsGC13M095091.
HGNCHGNC:2709. DCT.
HPACAB017634.
HPA010743.
HPA010800.
MIM191275. gene.
neXtProtNX_P40126.
PharmGKBPA27179.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301916.
HOGENOMHOG000118376.
HOVERGENHBG003553.
InParanoidP40126.
KOK01827.
OMAWPRKFFN.
OrthoDBEOG7TJ3HG.
PhylomeDBP40126.
TreeFamTF315865.

Enzyme and pathway databases

UniPathwayUPA00785.

Gene expression databases

ArrayExpressP40126.
BgeeP40126.
CleanExHS_DCT.
GenevestigatorP40126.

Family and domain databases

Gene3D1.10.1280.10. 1 hit.
InterProIPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view]
PfamPF00264. Tyrosinase. 1 hit.
[Graphical view]
PRINTSPR00092. TYROSINASE.
SUPFAMSSF48056. SSF48056. 1 hit.
PROSITEPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDopachrome_tautomerase.
GenomeRNAi1638.
NextBio6730.
PROP40126.
SOURCESearch...

Entry information

Entry nameTYRP2_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 138 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM