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Q13115 (DUS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Dual specificity protein phosphatase 4

EC=3.1.3.16
EC=3.1.3.48
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 names
Name:DUSP4
Synonyms:MKP2, VH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length394 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Subunit structure

Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit. Ref.11

Subcellular location

Nucleus.

Post-translational modification

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

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.

Contains 1 rhodanese domain.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Traceable author statement Ref.1. Source: ProtInc

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

endoderm formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

inactivation of MAPK activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

innate immune response

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

protein dephosphorylation

Inferred from Biological aspect of Ancestor. Source: RefGenome

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 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

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionMAP kinase tyrosine/serine/threonine phosphatase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein tyrosine/threonine phosphatase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13115-1)

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.
Isoform 2 (identifier: Q13115-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 394394Dual specificity protein phosphatase 4
PRO_0000094798

Regions

Domain41 – 159119Rhodanese
Domain197 – 394198Tyrosine-protein phosphatase

Sites

Active site2801Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue3861Phosphoserine; by MAPK Ref.8
Modified residue3911Phosphoserine; by MAPK

Natural variations

Alternative sequence1 – 5353MVTME…DCRPF → MGRKVHSNGSQFAEHSRSPR RTGRDCKPVRAPSMALGVSQ LAGRSRCLCSESQ in isoform 2.
VSP_044667
Alternative sequence54 – 14491Missing in isoform 2.
VSP_044668

Experimental info

Sequence conflict1111R → G in AAC50452. Ref.2

Secondary structure

........................... 394
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MKP-2-L) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 0603971759B6952E

FASTA39442,953
        10         20         30         40         50         60 
MVTMEELREM DCSVLKRLMN RDENGGGAGG SGSHGTLGLP SGGKCLLLDC RPFLAHSAGY 

        70         80         90        100        110        120 
ILGSVNVRCN TIVRRRAKGS VSLEQILPAE EEVRARLRSG LYSAVIVYDE RSPRAESLRE 

       130        140        150        160        170        180 
DSTVSLVVQA LRRNAERTDI CLLKGGYERF SSEYPEFCSK TKALAAIPPP VPPSATEPLD 

       190        200        210        220        230        240 
LGCSSCGTPL HDQGGPVEIL PFLYLGSAYH AARRDMLDAL GITALLNVSS DCPNHFEGHY 

       250        260        270        280        290        300 
QYKCIPVEDN HKADISSWFM EAIEYIDAVK DCRGRVLVHC QAGISRSATI CLAYLMMKKR 

       310        320        330        340        350        360 
VRLEEAFEFV KQRRSIISPN FSFMGQLLQF ESQVLATSCA AEAASPSGPL RERGKTPATP 

       370        380        390 
TSQFVFSFPV SVGVHSAPSS LPYLHSPITT SPSC 

« Hide

Isoform 2 (MKP-2-S) [UniParc].

Checksum: 3BFB1126F4CF000A
Show »

FASTA30332,993

References

« Hide 'large scale' references
[1]"Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase."
Guan K.-L., Butch E.
J. Biol. Chem. 270:7197-7203(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation."
Chu Y., Solski P.A., Khosravi-Far R., Der C.J., Kelly K.
J. Biol. Chem. 271:6497-6501(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , 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].
[7]"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: Skin and Uterus.
[8]"Post-translational regulation of mitogen-activated protein kinase phosphatase-2 (MKP-2) by ERK."
Peng D.J., Zhou J.Y., Wu G.S.
Cell Cycle 9:4650-4655(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-386 AND SER_391.
[9]"Differential regulation of MAP kinase activation by a novel splice variant of human MAP kinase phosphatase-2."
Cadalbert L.C., Sloss C.M., Cunningham M.R., Al-Mutairi M., McIntire A., Shipley J., Plevin R.
Cell. Signal. 22:357-365(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structure of the catalytic domain of human MKP-2 reveals a 24-mer assembly."
Jeong D.G., Jung S.K., Yoon T.S., Woo E.J., Kim J.H., Park B.C., Ryu S.E., Kim S.J.
Proteins 76:763-767(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 194-336, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001385.1. NM_001394.6.
NP_476499.1. NM_057158.3.
UniGeneHs.417962.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EZZX-ray2.90A/B/C/D/E/F194-336[»]
ProteinModelPortalQ13115.
SMRQ13115. Positions 9-336.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108179. 7 interactions.
IntActQ13115. 5 interactions.
MINTMINT-8217030.
STRING9606.ENSP00000240100.

Chemistry

ChEMBLCHEMBL2146343.

PTM databases

PhosphoSiteQ13115.

Polymorphism databases

DMDM2499745.

Proteomic databases

PaxDbQ13115.
PRIDEQ13115.

Protocols and materials databases

DNASU1846.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000240100; ENSP00000240100; ENSG00000120875. [Q13115-1]
ENST00000240101; ENSP00000240101; ENSG00000120875. [Q13115-2]
GeneID1846.
KEGGhsa:1846.
UCSCuc003xhl.3. human.
uc003xhm.3. human. [Q13115-1]

Organism-specific databases

CTD1846.
GeneCardsGC08M029190.
HGNCHGNC:3070. DUSP4.
MIM602747. gene.
neXtProtNX_Q13115.
PharmGKBPA27527.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2453.
HOVERGENHBG007347.
InParanoidQ13115.
KOK04459.
OMAHHSPITT.
OrthoDBEOG75MVWD.
PhylomeDBQ13115.
TreeFamTF105122.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkQ13115.

Gene expression databases

BgeeQ13115.
CleanExHS_DUSP4.
GenevestigatorQ13115.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
InterProIPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR008343. MKP.
IPR001763. Rhodanese-like_dom.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PANTHERPTHR10159. PTHR10159. 1 hit.
PfamPF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PIRSFPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSPR01764. MAPKPHPHTASE.
SMARTSM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF52821. SSF52821. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13115.
GeneWikiDUSP4.
GenomeRNAi1846.
NextBio7559.
PROQ13115.
SOURCESearch...

Entry information

Entry nameDUS4_HUMAN
AccessionPrimary (citable) accession number: Q13115
Secondary accession number(s): B2RBU5 expand/collapse secondary AC list , D3DSU4, G5E930, Q13524
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 135 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

MIM cross-references

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

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM