Homo sapiens Gene: MAP2K4
InnateDB Gene IDBG-31021.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol MAP2K4
Gene Name mitogen-activated protein kinase kinase 4
Species Homo sapiens
Ensembl Gene ENSG00000065559
Encoded Proteins
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Activates JNK proteins
Activated by MAP3K 2,3,4,5 (MEKK 2,3,4,5)
Activated by MAP3K 2,3,4,5 (MEKK 2,3,4,5)
Activated by MAP3K 2,3,4,5 (MEKK 2,3,4,5)
Entrez Gene
Summary This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK3. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver. [provided by RefSeq, Jul 2008]
This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Gene Information
Type Protein coding
Genomic Location Chromosome 17:12020824-12143830
Strand Forward strand
Band p12
ENST00000353533 ENSP00000262445
ENST00000415385 ENSP00000410402
ENST00000538465 ENSP00000467239
ENST00000582183 ENSP00000463507
ENST00000602811 ENSP00000473582
ENST00000602375 ENSP00000473472
ENST00000602305 ENSP00000473606
ENST00000602686 ENSP00000473458
ENST00000602537 ENSP00000473511
Number of Interactions This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.
Experimentally validated
Total 69 [view]
Protein-Protein 65 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 4 [view]
Predicted by orthology
Total 12 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004708 MAP kinase kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008545 JUN kinase kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0031435 mitogen-activated protein kinase kinase kinase binding
Biological Process
GO:0000165 MAPK cascade
GO:0001934 positive regulation of protein phosphorylation
GO:0002224 toll-like receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007254 JNK cascade
GO:0007257 activation of JUN kinase activity
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0043065 positive regulation of apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0045087 innate immune response (InnateDB)
GO:0045740 positive regulation of DNA replication
GO:0051403 stress-activated MAPK cascade
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0061049 cell growth involved in cardiac muscle cell development
GO:0071260 cellular response to mechanical stimulus
GO:0072709 cellular response to sorbitol
Cellular Component
GO:0005634 nucleus
GO:0005829 cytosol
GO:0030424 axon
GO:0032839 dendrite cytoplasm
GO:0043204 perikaryon
Mus musculus
Bos taurus
Gene ID
Gene Order
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Not yet available
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Wnt pathway
TNFalpha pathway
IL1 pathway
IL6 pathway
Cellular responses to stress pathway
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Uptake and actions of bacterial toxins pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Fc epsilon receptor (FCERI) signaling pathway
MAP kinase activation in TLR cascade pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
Cellular Senescence pathway
Signaling by Interleukins pathway
Interleukin-1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Oxidative Stress Induced Senescence pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Uptake and function of anthrax toxins pathway
Disease pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
FCERI mediated MAPK activation pathway
MAPK signaling pathway pathway
ErbB signaling pathway pathway
Toll-like receptor signaling pathway pathway
Fc epsilon RI signaling pathway pathway
GnRH signaling pathway pathway
Epithelial cell signaling in Helicobacter pylori infection pathway
Chagas disease (American trypanosomiasis) pathway
TNFR1 signaling pathway pathway
Fas signaling pathway pathway
TGF-beta signaling pathway
PDGF signaling pathway pathway
IL-7 signaling pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
JAK STAT pathway and regulation pathway
EPO signaling pathway pathway
VEGF signaling pathway pathway
EGF signaling pathway pathway
Inhibition of cellular proliferation by gleevec [Biocarta view]
Toll-like receptor pathway [Biocarta view]
Map kinase inactivation of smrt corepressor [Biocarta view]
Keratinocyte differentiation [Biocarta view]
Angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling [Biocarta view]
Tnfr1 signaling pathway [Biocarta view]
Pdgf signaling pathway [Biocarta view]
P38 mapk signaling pathway [Biocarta view]
Fas signaling pathway (cd95) [Biocarta view]
Tnf/stress related signaling [Biocarta view]
Mapkinase signaling pathway [Biocarta view]
Ceramide signaling pathway [Biocarta view]
Links between pyk2 and map kinases [Biocarta view]
T cell receptor signaling pathway [Biocarta view]
Egf signaling pathway [Biocarta view]
Fc epsilon receptor i signaling in mast cells [Biocarta view]
Nephrin/Neph1 signaling in the kidney podocyte
CD40/CD40L signaling
Ceramide signaling pathway
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
Cellular roles of Anthrax toxin
VEGFR3 signaling in lymphatic endothelium
TRAIL signaling pathway
ErbB1 downstream signaling
Signaling events mediated by focal adhesion kinase
RAC1 signaling pathway
Ephrin B reverse signaling
JNK signaling in the CD4+ TCR pathway
CDC42 signaling events
Regulation of p38-alpha and p38-beta
RhoA signaling pathway
Regulation of Androgen receptor activity
Fc-epsilon receptor I signaling in mast cells
IL6-mediated signaling events
SwissProt P45985
UniProt Splice Variant
Entrez Gene 6416
UniGene Hs.514681 Hs.598874 Hs.629818
RefSeq NM_001281435 XM_005256753 XM_005256755 XM_006721568 NM_003010
OMIM 601335
CCDS CCDS62095 CCDS11162
HPRD 03213
EMBL AC005244 AC005410 AF070080 AF070081 AF070082 AF070083 AF070084 AF070085 AF070086 AF070087 AF070088 AF070089 AF070090 AK131544 AK313053 BC036032 BC060764 BT019676 CH471108 CR536564 DQ015703 L36870 U17743
GenPept AAC24130 AAC41719 AAC50127 AAH36032 AAH60764 AAV38482 AAY22176 BAG35884 BAG54774 CAG38801 EAW89974 EAW89975 EAW89976
RNA Seq Atlas 6416