Q13115 (DUS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	394 AA.
Sequence status	Complete.
Protein existence	Evidence 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 phosphoprotein + H2O = a protein + phosphate.
Subunit structure	Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit. Ref.10
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 component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
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 TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome endoderm formation Inferred from Biological aspect of Ancestor. Source: RefGenome innate immune response Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC 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	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	MAP kinase tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome protein tyrosine phosphatase activity Inferred from electronic annotation. Source: 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 394

394

Dual specificity protein phosphatase 4

PRO_0000094798

Regions

Domain

41 – 159

119

Rhodanese

Domain

197 – 394

198

Tyrosine-protein phosphatase

Sites

Active site

280

1

Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue

386

1

Phosphoserine; by MAPK Ref.8

Modified residue

391

1

Phosphoserine; by MAPK

Natural variations

Alternative sequence

1 – 53

53

MVTME…DCRPF → MGRKVHSNGSQFAEHSRSPR RTGRDCKPVRAPSMALGVSQ LAGRSRCLCSESQ in isoform 2.

VSP_044667

Alternative sequence

54 – 144

91

Missing in isoform 2.

VSP_044668

Experimental info

Sequence conflict

111

1

R → G in AAC50452. Ref.2

Secondary structure

1

.

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394

Helix Strand Turn

Details...

Beta strand

197 – 200

4

Beta strand

203 – 207

5

Helix

208 – 211

4

Helix

214 – 219

6

Beta strand

224 – 227

4

Beta strand

229 – 231

3

Turn

235 – 239

5

Beta strand

240 – 244

5

Beta strand

249 – 252

4

Turn

255 – 258

4

Helix

259 – 271

13

Beta strand

276 – 285

10

Helix

286 – 299

14

Helix

303 – 311

9

Helix

321 – 335

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MKP-2-L) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 0603971759B6952E	FASTA	394	42,953
	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
	Isoform 2 (MKP-2-S) [UniParc]. Checksum: 3BFB1126F4CF000A	FASTA	303	32,993
	10 20 30 40 50 60 MGRKVHSNGS QFAEHSRSPR RTGRDCKPVR APSMALGVSQ LAGRSRCLCS ESQGGYERFS 70 80 90 100 110 120 SEYPEFCSKT KALAAIPPPV PPSATEPLDL GCSSCGTPLH DQGGPVEILP FLYLGSAYHA 130 140 150 160 170 180 ARRDMLDALG ITALLNVSSD CPNHFEGHYQ YKCIPVEDNH KADISSWFME AIEYIDAVKD 190 200 210 220 230 240 CRGRVLVHCQ AGISRSATIC LAYLMMKKRV RLEEAFEFVK QRRSIISPNF SFMGQLLQFE 250 260 270 280 290 300 SQVLATSCAA EAASPSGPLR ERGKTPATPT SQFVFSFPVS VGVHSAPSSL PYLHSPITTS PSC

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.

IPI

IPI00011860.

RefSeq

NP_001385.1. NM_001394.6.
NP_476499.1. NM_057158.3.

UniGene

Hs.417962.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EZZ	X-ray	2.90	A/B/C/D/E/F	194-336	[»]

ProteinModelPortal

Q13115.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000240100.

PTM databases

PhosphoSite

Q13115.

Polymorphism databases

DMDM

2499745.

Proteomic databases

PaxDb

Q13115.

PRIDE

Q13115.

Protocols and materials databases

DNASU

1846.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000240100; ENSP00000240100; ENSG00000120875.
ENST00000240101; ENSP00000240101; ENSG00000120875.

GeneID

1846.

KEGG

hsa:1846.

UCSC

uc003xhl.3. human.

Organism-specific databases

CTD

1846.

GeneCards

GC08M029190.

HGNC

HGNC:3070. DUSP4.

MIM

602747. gene.

neXtProt

NX_Q13115.

PharmGKB

PA27527.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2453.

HOVERGEN

HBG007347.

InParanoid

Q13115.

KO

K04459.

OMA

DNHKEDI.

OrthoDB

EOG4DZ1VF.

PhylomeDB

Q13115.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13115.

Bgee

Q13115.

CleanEx

HS_DUSP4.

Genevestigator

Q13115.

GermOnline

ENSG00000120875. Homo sapiens.

Family and domain databases

Gene3D

3.40.250.10. 1 hit.

InterPro

IPR000340. 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]

PANTHER

PTHR10159. PTHR10159. 1 hit.

Pfam

PF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]

PIRSF

PIRSF000939. MAPK_Ptase. 1 hit.

PRINTS

PR01764. MAPKPHPHTASE.

SMART

SM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]

SUPFAM

SSF52821. Rhodanese-like. 1 hit.

PROSITE

PS50206. RHODANESE_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q13115.

GenomeRNAi

1846.

NextBio

7559.

SOURCE

Search...

Entry information

Entry name

DUS4_HUMAN

Accession

Primary (citable) accession number: Q13115
Secondary accession number(s): B2RBU5 , D3DSU4, G5E930, Q13524

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 125 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.