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Protein

Dual specificity protein phosphatase 4

Gene

DUSP4

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

Functioni

Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation1 Publication
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei280Phosphocysteine intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • MAP kinase threonine phosphatase activity Source: UniProtKB
  • MAP kinase tyrosine/serine/threonine phosphatase activity Source: InterPro
  • phosphatase activity Source: UniProtKB
  • protein tyrosine/threonine phosphatase activity Source: UniProtKB
  • protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

  • dephosphorylation Source: UniProtKB
  • endoderm formation Source: GO_Central
  • inactivation of MAPK activity Source: UniProtKB
  • negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • peptidyl-threonine dephosphorylation Source: UniProtKB
  • peptidyl-tyrosine dephosphorylation Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiR-HSA-112409. RAF-independent MAPK1/3 activation.
R-HSA-202670. ERKs are inactivated.
R-HSA-5675221. Negative regulation of MAPK pathway.
SignaLinkiQ13115.
SIGNORiQ13115.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein phosphatase 4 (EC:3.1.3.161 Publication, EC:3.1.3.481 Publication)
Alternative name(s):
Dual specificity protein phosphatase hVH2
Mitogen-activated protein kinase phosphatase 2
Short name:
MAP kinase phosphatase 2
Short name:
MKP-2
Gene namesi
Name:DUSP4
Synonyms:MKP2, VH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000120875.8.
HGNCiHGNC:3070. DUSP4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1846.
OpenTargetsiENSG00000120875.
PharmGKBiPA27527.

Chemistry databases

ChEMBLiCHEMBL2146343.

Polymorphism and mutation databases

BioMutaiDUSP4.
DMDMi2499745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000947982 – 394Dual specificity protein phosphatase 4Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylvaline1 Publication1
Modified residuei386Phosphoserine; by MAPK1 Publication1
Modified residuei391Phosphoserine; by MAPK1 Publication1

Post-translational modificationi

Phosphorylation in the C-terminus by ERK1/2 inhibits proteasomal degradation and stabilizes the protein.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ13115.
PaxDbiQ13115.
PeptideAtlasiQ13115.
PRIDEiQ13115.

PTM databases

DEPODiQ13115.
iPTMnetiQ13115.
PhosphoSitePlusiQ13115.

Expressioni

Gene expression databases

BgeeiENSG00000120875.
CleanExiHS_DUSP4.
GenevisibleiQ13115. HS.

Organism-specific databases

HPAiHPA061967.

Interactioni

Subunit structurei

Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit.1 Publication

Protein-protein interaction databases

BioGridi108179. 39 interactors.
IntActiQ13115. 8 interactors.
MINTiMINT-8217030.
STRINGi9606.ENSP00000240100.

Chemistry databases

BindingDBiQ13115.

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi197 – 200Combined sources4
Beta strandi203 – 207Combined sources5
Helixi208 – 211Combined sources4
Helixi214 – 219Combined sources6
Beta strandi224 – 227Combined sources4
Beta strandi229 – 231Combined sources3
Turni235 – 239Combined sources5
Beta strandi240 – 244Combined sources5
Beta strandi249 – 252Combined sources4
Turni255 – 258Combined sources4
Helixi259 – 271Combined sources13
Beta strandi276 – 285Combined sources10
Helixi286 – 299Combined sources14
Helixi303 – 311Combined sources9
Helixi321 – 335Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EZZX-ray2.90A/B/C/D/E/F194-336[»]
ProteinModelPortaliQ13115.
SMRiQ13115.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13115.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 159RhodanesePROSITE-ProRule annotationAdd BLAST119
Domaini197 – 394Tyrosine-protein phosphataseAdd BLAST198

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1716. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00760000118902.
HOVERGENiHBG007347.
InParanoidiQ13115.
KOiK04459.
OMAiHKEDISC.
OrthoDBiEOG091G0249.
PhylomeDBiQ13115.
TreeFamiTF105122.

Family and domain databases

CDDicd00127. DSPc. 1 hit.
Gene3Di3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProiView protein in InterPro
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiView protein in Pfam
PF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
PIRSFiPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSiPR01764. MAPKPHPHTASE.
SMARTiView protein in SMART
SM00195. DSPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
SM00450. RHOD. 1 hit.
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEiView protein in PROSITE
PS50206. RHODANESE_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.

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. AlignAdd to basket

Isoform 1 (identifier: Q13115-1) [UniParc]FASTAAdd to basket
Also known as: MKP-2-L

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
MVTMEELREM DCSVLKRLMN RDENGGGAGG SGSHGTLGLP SGGKCLLLDC
60 70 80 90 100
RPFLAHSAGY ILGSVNVRCN TIVRRRAKGS VSLEQILPAE EEVRARLRSG
110 120 130 140 150
LYSAVIVYDE RSPRAESLRE DSTVSLVVQA LRRNAERTDI CLLKGGYERF
160 170 180 190 200
SSEYPEFCSK TKALAAIPPP VPPSATEPLD LGCSSCGTPL HDQGGPVEIL
210 220 230 240 250
PFLYLGSAYH AARRDMLDAL GITALLNVSS DCPNHFEGHY QYKCIPVEDN
260 270 280 290 300
HKADISSWFM EAIEYIDAVK DCRGRVLVHC QAGISRSATI CLAYLMMKKR
310 320 330 340 350
VRLEEAFEFV KQRRSIISPN FSFMGQLLQF ESQVLATSCA AEAASPSGPL
360 370 380 390
RERGKTPATP TSQFVFSFPV SVGVHSAPSS LPYLHSPITT SPSC
Length:394
Mass (Da):42,953
Last modified:November 1, 1996 - v1
Checksum:i0603971759B6952E
GO
Isoform 2 (identifier: Q13115-2) [UniParc]FASTAAdd to basket
Also known as: MKP-2-S

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MVTMEELREM...KCLLLDCRPF → MGRKVHSNGS...RSRCLCSESQ
     54-144: Missing.

Note: Does not bind to JNK or ERK, and is more susceptible to proteosomal degradation.
Show »
Length:303
Mass (Da):32,993
Checksum:i3BFB1126F4CF000A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti111R → G in AAC50452 (PubMed:8626452).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0446671 – 53MVTME…DCRPF → MGRKVHSNGSQFAEHSRSPR RTGRDCKPVRAPSMALGVSQ LAGRSRCLCSESQ in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_04466854 – 144Missing in isoform 2. 1 PublicationAdd BLAST91

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U21108 mRNA. Translation: AAA85119.1.
U48807 mRNA. Translation: AAC50452.1.
AK314820 mRNA. Translation: BAG37342.1.
AL137704 mRNA. No translation available.
AC084262 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63481.1.
CH471080 Genomic DNA. Translation: EAW63482.1.
CH471080 Genomic DNA. Translation: EAW63483.1.
CH471080 Genomic DNA. Translation: EAW63484.1.
BC002671 mRNA. Translation: AAH02671.1.
BC014565 mRNA. Translation: AAH14565.1.
CCDSiCCDS6072.1. [Q13115-1]
CCDS6073.1. [Q13115-2]
RefSeqiNP_001385.1. NM_001394.6. [Q13115-1]
NP_476499.1. NM_057158.3. [Q13115-2]
XP_011542730.1. XM_011544428.2. [Q13115-2]
UniGeneiHs.417962.

Genome annotation databases

EnsembliENST00000240100; ENSP00000240100; ENSG00000120875. [Q13115-1]
ENST00000240101; ENSP00000240101; ENSG00000120875. [Q13115-2]
GeneIDi1846.
KEGGihsa:1846.
UCSCiuc003xhl.4. human. [Q13115-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDUS4_HUMAN
AccessioniPrimary (citable) accession number: Q13115
Secondary accession number(s): B2RBU5
, D3DSU4, G5E930, Q13524
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: September 27, 2017
This is version 165 of the entry and version 1 of the sequence. See 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 8
    Human chromosome 8: 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