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Protein

Dual specificity protein phosphatase 3

Gene

DUSP3

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

Functioni

Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.2 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei124 – 1241Phosphocysteine intermediate

GO - Molecular functioni

  1. MAP kinase phosphatase activity Source: UniProtKB
  2. protein kinase binding Source: MGI
  3. protein tyrosine/serine/threonine phosphatase activity Source: UniProtKB
  4. protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

  1. inactivation of MAPK activity Source: UniProtKB
  2. innate immune response Source: Reactome
  3. in utero embryonic development Source: Ensembl
  4. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  5. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  6. negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  7. negative regulation of JNK cascade Source: UniProtKB
  8. negative regulation of MAPK cascade Source: UniProtKB
  9. negative regulation of T cell activation Source: UniProtKB
  10. negative regulation of T cell receptor signaling pathway Source: UniProtKB
  11. neurotrophin TRK receptor signaling pathway Source: Reactome
  12. peptidyl-tyrosine dephosphorylation Source: UniProtKB
  13. positive regulation of mitotic cell cycle Source: UniProtKB
  14. stress-activated MAPK cascade Source: Reactome
  15. toll-like receptor 10 signaling pathway Source: Reactome
  16. toll-like receptor 2 signaling pathway Source: Reactome
  17. toll-like receptor 3 signaling pathway Source: Reactome
  18. toll-like receptor 4 signaling pathway Source: Reactome
  19. toll-like receptor 5 signaling pathway Source: Reactome
  20. toll-like receptor 9 signaling pathway Source: Reactome
  21. toll-like receptor signaling pathway Source: Reactome
  22. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  23. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  24. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiREACT_12436. ERKs are inactivated.
SignaLinkiP51452.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein phosphatase 3 (EC:3.1.3.16, EC:3.1.3.48)
Alternative name(s):
Dual specificity protein phosphatase VHR
Vaccinia H1-related phosphatase
Short name:
VHR
Gene namesi
Name:DUSP3
Synonyms:VHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:3069. DUSP3.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: UniProtKB
  3. extracellular vesicular exosome Source: UniProtKB
  4. immunological synapse Source: UniProtKB
  5. nucleoplasm Source: HPA
  6. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27526.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 185185Dual specificity protein phosphatase 3PRO_0000094795Add
BLAST

Proteomic databases

MaxQBiP51452.
PaxDbiP51452.
PRIDEiP51452.

2D gel databases

UCD-2DPAGEP51452.

PTM databases

DEPODiP51452.
PhosphoSiteiP51452.

Expressioni

Gene expression databases

BgeeiP51452.
CleanExiHS_DUSP3.
ExpressionAtlasiP51452. baseline and differential.
GenevestigatoriP51452.

Organism-specific databases

HPAiCAB025265.

Interactioni

Subunit structurei

Interacts with VRK3, which seems to activate it's phosphatase activity.By similarity

Protein-protein interaction databases

BioGridi108178. 10 interactions.
IntActiP51452. 5 interactions.
MINTiMINT-5001069.
STRINGi9606.ENSP00000226004.

Structurei

Secondary structure

1
185
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi8 – 169Combined sources
Beta strandi19 – 213Combined sources
Beta strandi27 – 348Combined sources
Beta strandi37 – 404Combined sources
Helixi42 – 454Combined sources
Helixi48 – 547Combined sources
Beta strandi58 – 614Combined sources
Beta strandi64 – 674Combined sources
Helixi76 – 783Combined sources
Turni79 – 824Combined sources
Beta strandi84 – 874Combined sources
Helixi98 – 1014Combined sources
Helixi102 – 11413Combined sources
Turni115 – 1173Combined sources
Beta strandi120 – 1234Combined sources
Beta strandi125 – 1295Combined sources
Helixi130 – 14314Combined sources
Helixi147 – 15711Combined sources
Helixi164 – 17916Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J4XX-ray2.75A2-185[»]
1VHRX-ray2.10A/B2-185[»]
3F81X-ray1.90A/B3-185[»]
ProteinModelPortaliP51452.
SMRiP51452. Positions 7-185.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51452.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini99 – 16971Tyrosine-protein phosphataseAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG2453.
GeneTreeiENSGT00760000118853.
HOGENOMiHOG000233767.
HOVERGENiHBG001524.
InParanoidiP51452.
KOiK17614.
OMAiITYHGIK.
OrthoDBiEOG7CZK7N.
PhylomeDBiP51452.
TreeFamiTF105128.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR020417. Atypical_DUSP.
IPR020405. Atypical_DUSP_famA.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00782. DSPc. 1 hit.
[Graphical view]
PRINTSiPR01908. ADSPHPHTASE.
PR01909. ADSPHPHTASEA.
SMARTiSM00195. DSPc. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P51452-1) [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
MSGSFELSVQ DLNDLLSDGS GCYSLPSQPC NEVTPRIYVG NASVAQDIPK
60 70 80 90 100
LQKLGITHVL NAAEGRSFMH VNTNANFYKD SGITYLGIKA NDTQEFNLSA
110 120 130 140 150
YFERAADFID QALAQKNGRV LVHCREGYSR SPTLVIAYLM MRQKMDVKSA
160 170 180
LSIVRQNREI GPNDGFLAQL CQLNDRLAKE GKLKP
Length:185
Mass (Da):20,478
Last modified:October 1, 1996 - v1
Checksum:iC1045DD9B226FD94
GO
Isoform 2 (identifier: P51452-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MSGSFELSVQDLNDLLSDGSGCYSLPSQPCNEVTPRIYVGNA → M

Note: No experimental confirmation available.

Show »
Length:144
Mass (Da):16,163
Checksum:i21CA189AF19D20B3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4242MSGSF…YVGNA → M in isoform 2. 1 PublicationVSP_056284Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05147 mRNA. Translation: AAA35777.1.
BT019522 mRNA. Translation: AAV38329.1.
CH471178 Genomic DNA. Translation: EAW51667.1.
CH471178 Genomic DNA. Translation: EAW51668.1.
BC002682 mRNA. Translation: AAH02682.1.
BC035701 mRNA. Translation: AAH35701.1.
AC003098 Genomic DNA. No translation available.
AC055813 Genomic DNA. No translation available.
CCDSiCCDS11469.1. [P51452-1]
PIRiA47196.
RefSeqiNP_004081.1. NM_004090.3. [P51452-1]
UniGeneiHs.181046.

Genome annotation databases

EnsembliENST00000226004; ENSP00000226004; ENSG00000108861. [P51452-1]
GeneIDi1845.
KEGGihsa:1845.
UCSCiuc002ied.4. human. [P51452-1]

Polymorphism databases

DMDMi1718191.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05147 mRNA. Translation: AAA35777.1.
BT019522 mRNA. Translation: AAV38329.1.
CH471178 Genomic DNA. Translation: EAW51667.1.
CH471178 Genomic DNA. Translation: EAW51668.1.
BC002682 mRNA. Translation: AAH02682.1.
BC035701 mRNA. Translation: AAH35701.1.
AC003098 Genomic DNA. No translation available.
AC055813 Genomic DNA. No translation available.
CCDSiCCDS11469.1. [P51452-1]
PIRiA47196.
RefSeqiNP_004081.1. NM_004090.3. [P51452-1]
UniGeneiHs.181046.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J4XX-ray2.75A2-185[»]
1VHRX-ray2.10A/B2-185[»]
3F81X-ray1.90A/B3-185[»]
ProteinModelPortaliP51452.
SMRiP51452. Positions 7-185.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108178. 10 interactions.
IntActiP51452. 5 interactions.
MINTiMINT-5001069.
STRINGi9606.ENSP00000226004.

Chemistry

BindingDBiP51452.
ChEMBLiCHEMBL2635.

PTM databases

DEPODiP51452.
PhosphoSiteiP51452.

Polymorphism databases

DMDMi1718191.

2D gel databases

UCD-2DPAGEP51452.

Proteomic databases

MaxQBiP51452.
PaxDbiP51452.
PRIDEiP51452.

Protocols and materials databases

DNASUi1845.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226004; ENSP00000226004; ENSG00000108861. [P51452-1]
GeneIDi1845.
KEGGihsa:1845.
UCSCiuc002ied.4. human. [P51452-1]

Organism-specific databases

CTDi1845.
GeneCardsiGC17M041843.
H-InvDBHIX0013868.
HGNCiHGNC:3069. DUSP3.
HPAiCAB025265.
MIMi600183. gene.
neXtProtiNX_P51452.
PharmGKBiPA27526.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2453.
GeneTreeiENSGT00760000118853.
HOGENOMiHOG000233767.
HOVERGENiHBG001524.
InParanoidiP51452.
KOiK17614.
OMAiITYHGIK.
OrthoDBiEOG7CZK7N.
PhylomeDBiP51452.
TreeFamiTF105128.

Enzyme and pathway databases

ReactomeiREACT_12436. ERKs are inactivated.
SignaLinkiP51452.

Miscellaneous databases

ChiTaRSiDUSP3. human.
EvolutionaryTraceiP51452.
GeneWikiiDUSP3.
GenomeRNAii1845.
NextBioi7555.
PROiP51452.
SOURCEiSearch...

Gene expression databases

BgeeiP51452.
CleanExiHS_DUSP3.
ExpressionAtlasiP51452. baseline and differential.
GenevestigatoriP51452.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR020417. Atypical_DUSP.
IPR020405. Atypical_DUSP_famA.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00782. DSPc. 1 hit.
[Graphical view]
PRINTSiPR01908. ADSPHPHTASE.
PR01909. ADSPHPHTASEA.
SMARTiSM00195. DSPc. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Duodenum and Uterus.
  6. "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway."
    Todd J.L., Tanner K.G., Denu J.M.
    J. Biol. Chem. 274:13271-13280(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Crystal structure of the dual specificity protein phosphatase VHR."
    Yuvaniyama J., Denu J.M., Dixon J.E., Saper M.A.
    Science 272:1328-1331(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
  9. "Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase."
    Schumacher M.A., Todd J.L., Rice A.E., Tanner K.G., Denu J.M.
    Biochemistry 41:3009-3017(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 2-185, FUNCTION.
  10. "Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells."
    Wu S., Vossius S., Rahmouni S., Miletic A.V., Vang T., Vazquez-Rodriguez J., Cerignoli F., Arimura Y., Williams S., Hayes T., Moutschen M., Vasile S., Pellecchia M., Mustelin T., Tautz L.
    J. Med. Chem. 52:6716-6723(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 3-185.

Entry informationi

Entry nameiDUS3_HUMAN
AccessioniPrimary (citable) accession number: P51452
Secondary accession number(s): D3DX45, Q5U0J1, Q8IYJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 4, 2015
This is version 142 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 17
    Human chromosome 17: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.