P51452 (DUS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	DUSP3
Synonyms:	VHR

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	185 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5 Ref.8
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. A phosphoprotein + H2O = a protein + phosphate.
Subunit structure	Interacts with VRK3, which seems to activate it's phosphatase activity By similarity.
Subcellular location	Nucleus Ref.5.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
Cellular component	Nucleus
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome inactivation of MAPK activity Inferred from mutant phenotype. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome negative regulation of ERK1 and ERK2 cascade Inferred from direct assay. Source: UniProtKB negative regulation of JNK cascade Inferred from direct assay. Source: UniProtKB negative regulation of T cell activation Inferred from direct assay. Source: UniProtKB negative regulation of T cell receptor signaling pathway Inferred from direct assay. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of mitotic cell cycle Inferred from mutant phenotype. Source: UniProtKB stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB immunological synapse Inferred from direct assay. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular function	MAP kinase phosphatase activity Inferred from mutant phenotype. Source: UniProtKB protein tyrosine phosphatase activity Inferred from direct assay Ref.8. Source: UniProtKB protein tyrosine/serine/threonine phosphatase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 185

185

Dual specificity protein phosphatase 3

PRO_0000094795

Regions

Domain

99 – 169

71

Tyrosine-protein phosphatase

Sites

Active site

124

1

Phosphocysteine intermediate

Secondary structure

1

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185

Helix Strand Turn

Details...

Helix

9 – 16

8

Beta strand

17 – 21

5

Beta strand

27 – 34

8

Beta strand

37 – 40

4

Helix

42 – 45

4

Helix

48 – 54

7

Beta strand

58 – 61

4

Beta strand

64 – 67

4

Helix

75 – 78

4

Turn

79 – 82

4

Beta strand

84 – 87

4

Helix

98 – 101

4

Helix

102 – 113

12

Beta strand

120 – 123

4

Beta strand

125 – 129

5

Helix

130 – 142

13

Helix

147 – 157

11

Helix

164 – 179

16

Sequences

	Sequence		Length	Mass (Da)
	P51452 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: C1045DD9B226FD94	FASTA	185	20,478
	10 20 30 40 50 60 MSGSFELSVQ DLNDLLSDGS GCYSLPSQPC NEVTPRIYVG NASVAQDIPK LQKLGITHVL 70 80 90 100 110 120 NAAEGRSFMH VNTNANFYKD SGITYLGIKA NDTQEFNLSA YFERAADFID QALAQKNGRV 130 140 150 160 170 180 LVHCREGYSR SPTLVIAYLM MRQKMDVKSA LSIVRQNREI GPNDGFLAQL CQLNDRLAKE GKLKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression cloning of a human dual-specificity phosphatase." Ishibashi T., Bottaro D.P., Chan A., Miki T., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 89:12170-12174(1992) [PubMed: 1281549] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Uterus.
[5]	"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: 10224087] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"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: 8650541] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[8]	"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: 11863439] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 2-185, FUNCTION.
[9]	"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: 19888758] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 3-185.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00018671.

PIR

A47196.

RefSeq

NP_004081.1. NM_004090.3.

UniGene

Hs.181046.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J4X	X-ray	2.75	A	2-185	[»]
1VHR	X-ray	2.10	A/B	2-185	[»]
3F81	X-ray	1.90	A/B	3-185	[»]

ProteinModelPortal

P51452.

SMR

P51452. Positions 7-185.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51452. 3 interactions.

STRING

P51452.

PTM databases

PhosphoSite

P51452.

Polymorphism databases

DMDM

1718191.

2D gel databases

UCD-2DPAGE

P51452.

Proteomic databases

PRIDE

P51452.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000226004; ENSP00000226004; ENSG00000108861.

GeneID

1845.

KEGG

hsa:1845.

UCSC

uc002ied.2. human.

Organism-specific databases

CTD

1845.

GeneCards

GC17M041856.

H-InvDB

HIX0202440.

HGNC

HGNC:3069. DUSP3.

HPA

CAB025265.

MIM

600183. gene.

neXtProt

NX_P51452.

PharmGKB

PA27526.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17568.

HOGENOM

HBG717377.

HOVERGEN

HBG001524.

InParanoid

P51452.

OMA

QLCQLNE.

OrthoDB

EOG46Q6TP.

PhylomeDB

P51452.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P51452.

Bgee

P51452.

CleanEx

HS_DUSP3.

Genevestigator

P51452.

GermOnline

ENSG00000108861. Homo sapiens.

Family and domain databases

InterPro

IPR020417. Dual-sp_phosphatase.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR020405. Dual-sp_phosphatase_famA.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR000387. Tyr/Dual-specificity_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]

KO

K04459.

Pfam

PF00782. DSPc. 1 hit.
[Graphical view]

PRINTS

PR01908. ADSPHPHTASE.
PR01909. ADSPHPHTASEA.

SMART

SM00195. DSPc. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

7555.

SOURCE

Search...

Entry information

Entry name

DUS3_HUMAN

Accession

Primary (citable) accession number: P51452
Secondary accession number(s): D3DX45, Q5U0J1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
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.