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MAPK4 (mitogen-activated protein kinase 4)

Identity

Other namesextracellular signal-regulated kinase 4
ERK4
PRKM4
pP63mapk
ERK3-related
HGNC (Hugo) MAPK4
Location 18q21.1
Location_base_pair Starts at 46340482 and ends at 46512194 bp from pter ( according to hg18-Mar_2006)  [Mapping]
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 (Hugo)MAPK4   6878
Entrez_Gene (NCBI)MAPK4  5596  mitogen-activated protein kinase 4
Cards
AtlasMAPK4ID41293ch18q21
GeneCards (Weizmann)MAPK4
Ensembl (Hinxton)ENSG00000141639 [Gene_View]  MAPK4 [Vega]
AceView (NCBI)MAPK4
Genatlas (Paris)MAPK4
euGene (Indiana)5596
SOURCE (Stanford)NM_002747
Gene Expression (Array Express) ENSG00000141639
Genomic and cartography
GoldenPath (UCSC)MAPK4  -  18q21.1   chr18:46340482-46512194 +  18q12-q21   [Description]    (hg18-Mar_2006)
EnsemblMAPK4 - 18q12-q21 [CytoView]
Mapping of homologs : NCBIMAPK4 [Mapview]
OMIM176949   
Gene and transcription
Gene : Genbank (Entrez)AI088913 AK293818 AK295058 AK303601 BC040493
Reference sequence (RefSeq transcript) :SRSNM_002747
Reference transcript : EntrezNM_002747
RefSeq genomic : SRSAC_000061 AC_000150 NC_000018 NT_010966 NW_001838468 NW_927106
RefSeq genomic : EntrezAC_000061 AC_000150 NC_000018 NT_010966 NW_001838468 NW_927106
Consensus coding sequences : CCDS NCBIMAPK4
Cluster EST : UnigeneHs.433728 [ SRS ] Hs.433728 [ NCBI ]
Alternative Splicing : Fast-db (Paris)4500
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP31152 (SRS) P31152 (Expasy) P31152 (Uniprot)
With graphics : InterProP31152
Splice isoforms : VarSplice FASTAP31152(VarSplice FASTA)
Domaine pattern : Prosite (SRS)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domain pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (SRS)Erk_3_4_MAPK    Kinase-like_dom    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Se/Thr_prot_kinase-like_dom    Ser/Thr_prot_kinase_AS    Ser/Thr_prot_kinase_dom   
Domains : Interpro (EBI)Erk_3_4_MAPK    Kinase-like_dom    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Se/Thr_prot_kinase-like_dom    Ser/Thr_prot_kinase_AS    Ser/Thr_prot_kinase_dom   
Related proteins : CluSTrP31152
Domain families : Pfam SRSPkinase (PF00069)   
Domain families : Pfam SangerPkinase (PF00069)   
Domain families : Pfam NCBIpfam00069   
Domain families : Smart EMBLS_TKc (SM00220)  
Blocks (Seattle)P31152
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD01497
Protein Interaction databases
DIP (DOE-UCLA)P31152
IntAct (EBI)P31152
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIMAPK4
SNP : GeneSNP UtahMAPK4
SNP : HGBaseMAPK4
Genetic variants : HAPMAPMAPK4
Somatic Mutations in Cancer : COSMICMAPK4 
Mutations and Diseases : HGMDMAPK4
Hereditary diseases : OMIM176949   
Hereditary diseases : GENETests176949   
Diseases : Genetic AssociationMAPK4
General knowledge
Homologs : HomoloGeneMAPK4
Homology/Alignments : Family Browser UCSCMAPK4
Phylogenetic Trees/Animal Genes : TreeFamMAPK4
Catalytic activity : Enzyme2.7.11.24 [ Enzyme-Expasy ]   2.7.11.24 [ Enzyme-SRS ]   2.7.11.24 [ IntEnz-EBI ]   2.7.11.24 [ BRENDA ]   2.7.11.24 [ KEGG ]   
Chemical/Protein Interactions : CTD5596
Keywords Ontology : AmiGOnucleotide binding  protein serine/threonine kinase activity  MAP kinase activity  ATP binding  protein amino acid phosphorylation  cell cycle  transferase activity  
Keywords Ontology : EGO-EBInucleotide binding  protein serine/threonine kinase activity  MAP kinase activity  ATP binding  protein amino acid phosphorylation  cell cycle  transferase activity  
Pathways : BIOCARTAMAPKinase Signaling Pathway [Genes]   
Pathways : KEGG
Other databases
Probes
Probes : ImagenesMAPK4 Related clones (RZPD - Berlin)
Literature
PubMed16 Pubmed reference(s) in Entrez
PubGeneMAPK4

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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2008Sylvain 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

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indexed on : Sat Feb 27 10:49:45 CET 2010

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