MAPK4 (mitogen-activated protein kinase 4)

Identity

Other names	extracellular signal-regulated kinase 4
	ERK4
	PRKM4
	pP63mapk
	ERK3-related
HGNC	MAPK4
Location	18q21.1
Local_order	The MAPK4 gene is located between the genes C18orf24 and MRO on chromosome 18

DNA/RNA

	Figure 1. Genomic organization of the MAPK4 gene on chromosome 18.
Description	The MAPK4 gene spans 171.7 kb on the long arm of chromosome 18 and is transcribed in the centromere-to-telomere orientation. The gene is composed of 6 exons with the translation initiation codon located in exon 2. The first two exons are separated by a long intron of 102.8 kb.
Transcription	The MAPK4 transcribed mRNA has 4,736 bp. No splice variants have been reported.
Pseudogene	None.

Protein

	Figure 2. Schematic representation of the ERK4 protein structure. Kinase, catalytic kinase domain; C34 conserved region in ERK3 and ERK4; SEG, activation loop motif containing the regulatory phosphorylation residue Ser186.

Description	Extracellular signal-regulated kinase 4 (ERK4) is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. The human ERK4 protein is made of 587 amino acids and contains a typical kinase domain located at the N-terminal extremity. Another region with homology to the MAP kinase ERK3 (C34 domain) has been identified after the kinase domain. The function of the C34 domain is unknown.
Expression	MAPK4 mRNA is expressed to the highest level in the brain. Other sites of expression include the heart, lung, kidney, intestine, pancreas, parathyroid gland, prostate, thymus, ovary, eye and ear.
Localisation	ERK4 localizes to the cytoplasm and nucleus of a variety of cultured cells.
Function	Little is known about the regulation and functions of ERK4. The only known substrate of ERK4 is the protein kinase MK5.
Homology	ERK4 display 73% amino acid identity with ERK3 in the kinase domain. ERK4 and ERK3 define a distinct subfamily of MAP kinases that is found exclusively in vertebrates.

Mutations

Note	No mutation reported yet.

Implicated in

Entity	Cancer
Note	The expression of MAPK4 mRNA is down-regulated in bladder and squamous cell carcinomas (Oncomine 3.0). A chromosomal subregion containing the MAPK4 gene show recurrent copy number loss in pancreatic adenocarcinoma cell lines.

External links

	Nomenclature
HGNC	MAPK4   6878
Entrez_Gene	MAPK4  5596  mitogen-activated protein kinase 4
	Cards
Atlas	MAPK4ID41293ch18q21
GeneCards	MAPK4
Ensembl	MAPK4 [Search_View]   ENSG00000141639 [Gene_View]
Genatlas	MAPK4
GeneLynx	MAPK4
eGenome	MAPK4
euGene	5596
	Genomic and cartography
GoldenPath	MAPK4  -  18q21.1   chr18:46340482-46512194 +  18q21.2   [Description]    (hg18-Mar_2006)
Ensembl	MAPK4 - 18q21.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	MAPK4
	Gene and transcription
Genbank	AI088913 [ ENTREZ ]
Genbank	AK295058 [ ENTREZ ]
Genbank	BC040493 [ ENTREZ ]
Genbank	BC050299 [ ENTREZ ]
Genbank	BC117216 [ ENTREZ ]
RefSeq	NM_002747 [ SRS ]    NM_002747 [ ENTREZ ]
RefSeq	AC_000061 [ SRS ]    AC_000061 [ ENTREZ ]
RefSeq	AC_000150 [ SRS ]    AC_000150 [ ENTREZ ]
RefSeq	NC_000018 [ SRS ]    NC_000018 [ ENTREZ ]
RefSeq	NT_010966 [ SRS ]    NT_010966 [ ENTREZ ]
RefSeq	NW_001838468 [ SRS ]    NW_001838468 [ ENTREZ ]
RefSeq	NW_927106 [ SRS ]    NW_927106 [ ENTREZ ]
AceView	MAPK4 AceView - NCBI
Unigene	Hs.433728 [ SRS ]    Hs.433728 [ NCBI ]     HS433728 [ spliceNest ]
Fast-db	4500 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P31152 [ SRS]    P31152 [ EXPASY ]     P31152 [ INTERPRO ]     P31152 [ UNIPROT ]
Prosite	PS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
Prosite	PS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
Prosite	PS00108 PROTEIN_KINASE_ST [ SRS ]    PS00108 PROTEIN_KINASE_ST [ Expasy ]
Interpro	IPR008350 Erk_3_4_MAPK [ SRS ]    IPR008350 Erk_3_4_MAPK [ EBI ]
Interpro	IPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
Interpro	IPR017441 Protein_kinase_ATP_bd_CS [ SRS ]    IPR017441 Protein_kinase_ATP_bd_CS [ EBI ]
Interpro	IPR017442 Se/Thr_pkinase-rel [ SRS ]    IPR017442 Se/Thr_pkinase-rel [ EBI ]
Interpro	IPR008271 Ser_thr_pkin_AS [ SRS ]    IPR008271 Ser_thr_pkin_AS [ EBI ]
Interpro	IPR002290 Ser_thr_pkinase [ SRS ]    IPR002290 Ser_thr_pkinase [ EBI ]
CluSTr	P31152
Pfam	PF00069 Pkinase [ SRS ]    PF00069 Pkinase [ Sanger ]    pfam00069 [ NCBI-CDD ]
Smart	SM00220 S_TKc [EMBL]
Prodom	PD000001 Prot_kinase[INRA-Toulouse]
Prodom	P31152 MK04_HUMAN [ Domain structure ]   P31152 MK04_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P31152
HPRD	01497
	Protein Interaction databases
DIP	P31152
IntAct	P31152
	Polymorphism : SNP, mutations, diseases
OMIM	176949    [ map ]
GENECLINICS	176949
SNP	MAPK4 [dbSNP-NCBI]
SNP	NM_002747 [SNP-NCI]
SNP	MAPK4 [GeneSNPs - Utah]  MAPK4] [HGBASE - SRS]
HAPMAP	MAPK4 [HAPMAP]
COSMIC	MAPK4 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	MAPK4
	General knowledge
Family Browser	MAPK4 [UCSC Family Browser]
SOURCE	NM_002747
SMD	Hs.433728
SAGE	Hs.433728
Enzyme	2.7.11.24 [ Enzyme-Expasy ]   2.7.11.24 [ Enzyme-SRS ]   2.7.11.24 [ IntEnz-EBI ]   2.7.11.24 [ BRENDA ]   2.7.11.24 [ KEGG ]   2.7.11.24 [ WIT ]
GO	nucleotide binding [Amigo]  nucleotide binding
GO	protein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GO	MAP kinase activity [Amigo]  MAP kinase activity
GO	MAP kinase activity [Amigo]  MAP kinase activity
GO	ATP binding [Amigo]  ATP binding
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	cell cycle [Amigo]  cell cycle
GO	transferase activity [Amigo]  transferase activity
BIOCARTA	MAPKinase Signaling Pathway    [Genes]
PubGene	MAPK4
TreeFam	MAPK4
CTD	5596 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	MAPK4 Related clones (RZPD - Berlin)
	PubMed
PubMed	13 Pubmed reference(s) in LocusLink

Bibliography

Heterogeneous expression of four MAP kinase isoforms in human tissues.

Gonzalez FA, Raden DL, Rigby MR, Davis RJ.

FEBS Lett. 1992 Jun 15;304(2-3):170-8.

PMID 1319925

The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family.

Turgeon B, Lang BF, Meloche S.

Genomics. 2002 Dec;80(6):673-80.

PMID 12504858

Genome-wide aberrations in pancreatic adenocarcinoma.

Nowak NJ, Gaile D, Conroy JM, McQuaid D, Cowell J, Carter R, Goggins MG, Hruban RH, Maitra A.

Cancer Genet Cytogenet. 2005 Aug;161(1):36-50.

PMID 16080956

Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4.

Aberg E, Perander M, Johansen B, Julien C, Meloche S, Keyse SM, Seternes OM.

J Biol Chem. 2006 Nov 17;281(46):35499-510.

PMID 16971392

Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5.

Kant S, Schumacher S, Singh MK, Kispert A, Kotlyarov A, Gaestel M.

J Biol Chem. 2006 Nov 17;281(46):35511-9.

PMID 16973613

Atypical mitogen-activated protein kinases: structure, regulation and functions.

Coulombe P, Meloche S.

Biochim Biophys Acta. 2007 Aug;1773(8):1376-87. (REVIEW)

PMID 17161475

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	03-2008	Sylvain Meloche
		Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada

Citation

This paper should be referenced as such :

Meloche S . MAPK4 (mitogen-activated protein kinase 4). Atlas Genet Cytogenet Oncol Haematol. March 2008 . URL : http://AtlasGeneticsOncology.org/Genes/MAPK4ID41293ch18q21.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:15:12 2008