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P40126

- TYRP2_HUMAN

UniProt

P40126 - TYRP2_HUMAN

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Protein

L-dopachrome tautomerase

Gene

DCT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Involved in regulating eumelanin and phaeomelanin levels.

Catalytic activityi

L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.

Cofactori

Zn2+By similarityNote: Binds 2 Zn(2+) ions per subunit.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi189 – 1891Zinc ABy similarity
Metal bindingi211 – 2111Zinc ABy similarity
Metal bindingi220 – 2201Zinc ABy similarity
Metal bindingi369 – 3691Zinc BBy similarity
Metal bindingi373 – 3731Zinc BBy similarity
Metal bindingi396 – 3961Zinc BBy similarity

GO - Molecular functioni

  1. copper ion binding Source: ProtInc
  2. dopachrome isomerase activity Source: UniProtKB
  3. oxidoreductase activity Source: InterPro

GO - Biological processi

  1. cell development Source: Ensembl
  2. developmental pigmentation Source: Ensembl
  3. epidermis development Source: ProtInc
  4. melanin biosynthetic process from tyrosine Source: UniProtKB
  5. positive regulation of neuroblast proliferation Source: Ensembl
  6. ventricular zone neuroblast division Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Melanin biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00785.

Names & Taxonomyi

Protein namesi
Recommended name:
L-dopachrome tautomerase (EC:5.3.3.12)
Short name:
DCT
Short name:
DT
Alternative name(s):
L-dopachrome Delta-isomerase
Tyrosinase-related protein 2
Short name:
TRP-2
Short name:
TRP2
Gene namesi
Name:DCT
Synonyms:TYRP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 13

Organism-specific databases

HGNCiHGNC:2709. DCT.

Subcellular locationi

Melanosome membrane 2 Publications; Single-pass type I membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 472449Lumenal, melanosomeSequence AnalysisAdd
BLAST
Transmembranei473 – 49321HelicalSequence AnalysisAdd
BLAST
Topological domaini494 – 51926CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. integral component of membrane Source: ProtInc
  3. melanosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27179.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 519496L-dopachrome tautomerasePRO_0000035892Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi170 – 1701N-linked (GlcNAc...)Sequence Analysis
Glycosylationi178 – 1781N-linked (GlcNAc...)Sequence Analysis
Glycosylationi237 – 2371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi300 – 3001N-linked (GlcNAc...)Sequence Analysis
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
Glycosylationi377 – 3771N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP40126.
PRIDEiP40126.

PTM databases

PhosphoSiteiP40126.

Expressioni

Gene expression databases

BgeeiP40126.
CleanExiHS_DCT.
ExpressionAtlasiP40126. baseline and differential.
GenevestigatoriP40126.

Organism-specific databases

HPAiCAB017634.
HPA010743.
HPA010800.

Interactioni

Subunit structurei

Tyrosinase, TYRP1 and DCT/TYRP2 may form a multienzyme complex.By similarity

Protein-protein interaction databases

BioGridi108006. 1 interaction.
STRINGi9606.ENSP00000392762.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4HX1X-ray1.80C180-188[»]
ProteinModelPortaliP40126.
SMRiP40126. Positions 210-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tyrosinase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG301916.
GeneTreeiENSGT00500000044790.
HOGENOMiHOG000118376.
HOVERGENiHBG003553.
InParanoidiP40126.
KOiK01827.
OMAiWPRKFFN.
OrthoDBiEOG7TJ3HG.
PhylomeDBiP40126.
TreeFamiTF315865.

Family and domain databases

Gene3Di1.10.1280.10. 1 hit.
InterProiIPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view]
PfamiPF00264. Tyrosinase. 1 hit.
[Graphical view]
PRINTSiPR00092. TYROSINASE.
SUPFAMiSSF48056. SSF48056. 1 hit.
PROSITEiPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P40126-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MSPLWWGFLL SCLGCKILPG AQGQFPRVCM TVDSLVNKEC CPRLGAESAN
60 70 80 90 100
VCGSQQGRGQ CTEVRADTRP WSGPYILRNQ DDRELWPRKF FHRTCKCTGN
110 120 130 140 150
FAGYNCGDCK FGWTGPNCER KKPPVIRQNI HSLSPQEREQ FLGALDLAKK
160 170 180 190 200
RVHPDYVITT QHWLGLLGPN GTQPQFANCS VYDFFVWLHY YSVRDTLLGP
210 220 230 240 250
GRPYRAIDFS HQGPAFVTWH RYHLLCLERD LQRLIGNESF ALPYWNFATG
260 270 280 290 300
RNECDVCTDQ LFGAARPDDP TLISRNSRFS SWETVCDSLD DYNHLVTLCN
310 320 330 340 350
GTYEGLLRRN QMGRNSMKLP TLKDIRDCLS LQKFDNPPFF QNSTFSFRNA
360 370 380 390 400
LEGFDKADGT LDSQVMSLHN LVHSFLNGTN ALPHSAANDP IFVVLHSFTD
410 420 430 440 450
AIFDEWMKRF NPPADAWPQE LAPIGHNRMY NMVPFFPPVT NEELFLTSDQ
460 470 480 490 500
LGYSYAIDLP VSVEETPGWP TTLLVVMGTL VALVGLFVLL AFLQYRRLRK
510
GYTPLMETHL SSKRYTEEA
Length:519
Mass (Da):59,145
Last modified:February 1, 1995 - v1
Checksum:iAFDDF21768002A89
GO
Isoform 2 (identifier: P40126-2) [UniParc]FASTAAdd to Basket

Also known as: TRP-2-6b

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

Show »
Length:552
Mass (Da):62,929
Checksum:iF2B047A524167DD3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei393 – 3931V → VVISNRLLYNATTNILEHVR KEKATKELPSLHVL in isoform 2. 1 PublicationVSP_043581

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS45060.1. [P40126-2]
CCDS9470.1. [P40126-1]
PIRiS43510. YRHUR2.
RefSeqiNP_001123361.1. NM_001129889.1. [P40126-2]
NP_001913.2. NM_001922.3. [P40126-1]
UniGeneiHs.301865.

Genome annotation databases

EnsembliENST00000377028; ENSP00000366227; ENSG00000080166. [P40126-1]
ENST00000446125; ENSP00000392762; ENSG00000080166. [P40126-2]
GeneIDi1638.
KEGGihsa:1638.
UCSCiuc001vlv.4. human. [P40126-1]
uc010afh.3. human. [P40126-2]

Polymorphism databases

DMDMi731026.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS45060.1. [P40126-2 ]
CCDS9470.1. [P40126-1 ]
PIRi S43510. YRHUR2.
RefSeqi NP_001123361.1. NM_001129889.1. [P40126-2 ]
NP_001913.2. NM_001922.3. [P40126-1 ]
UniGenei Hs.301865.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4HX1 X-ray 1.80 C 180-188 [» ]
ProteinModelPortali P40126.
SMRi P40126. Positions 210-459.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108006. 1 interaction.
STRINGi 9606.ENSP00000392762.

PTM databases

PhosphoSitei P40126.

Polymorphism databases

DMDMi 731026.

Proteomic databases

PaxDbi P40126.
PRIDEi P40126.

Protocols and materials databases

DNASUi 1638.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000377028 ; ENSP00000366227 ; ENSG00000080166 . [P40126-1 ]
ENST00000446125 ; ENSP00000392762 ; ENSG00000080166 . [P40126-2 ]
GeneIDi 1638.
KEGGi hsa:1638.
UCSCi uc001vlv.4. human. [P40126-1 ]
uc010afh.3. human. [P40126-2 ]

Organism-specific databases

CTDi 1638.
GeneCardsi GC13M095091.
HGNCi HGNC:2709. DCT.
HPAi CAB017634.
HPA010743.
HPA010800.
MIMi 191275. gene.
neXtProti NX_P40126.
PharmGKBi PA27179.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG301916.
GeneTreei ENSGT00500000044790.
HOGENOMi HOG000118376.
HOVERGENi HBG003553.
InParanoidi P40126.
KOi K01827.
OMAi WPRKFFN.
OrthoDBi EOG7TJ3HG.
PhylomeDBi P40126.
TreeFami TF315865.

Enzyme and pathway databases

UniPathwayi UPA00785 .

Miscellaneous databases

GeneWikii Dopachrome_tautomerase.
GenomeRNAii 1638.
NextBioi 6730.
PROi P40126.
SOURCEi Search...

Gene expression databases

Bgeei P40126.
CleanExi HS_DCT.
ExpressionAtlasi P40126. baseline and differential.
Genevestigatori P40126.

Family and domain databases

Gene3Di 1.10.1280.10. 1 hit.
InterProi IPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view ]
Pfami PF00264. Tyrosinase. 1 hit.
[Graphical view ]
PRINTSi PR00092. TYROSINASE.
SUPFAMi SSF48056. SSF48056. 1 hit.
PROSITEi PS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    Tissue: Melanoma.
  10. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    Tissue: Melanoma.

Entry informationi

Entry nameiTYRP2_HUMAN
AccessioniPrimary (citable) accession number: P40126
Secondary accession number(s): Q09GT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 26, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3