Version 5.4
Homo sapiens Gene: MAP2K4
Summary
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
Synonyms JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4; SAPKK-1; SAPKK1; SEK1; SERK1; SKK1
Species Homo sapiens
Ensembl Gene ENSG00000065559
Encoded Proteins
IDBP-31023
mitogen-activated protein kinase kinase 4
IDBP-369000
mitogen-activated protein kinase kinase 4
IDBP-758620
IDBP-759639
IDBP-813566
mitogen-activated protein kinase kinase 4
IDBP-813567
mitogen-activated protein kinase kinase 4
IDBP-813568
mitogen-activated protein kinase kinase 4
IDBP-813569
mitogen-activated protein kinase kinase 4
IDBP-813570
mitogen-activated protein kinase kinase 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 10715136
Activates JNK proteins
PMID 11343802
Activated by MAP3K 2,3,4,5 (MEKK 2,3,4,5)
PMID 9841871
Activated by MAP3K 2,3,4,5 (MEKK 2,3,4,5)
PMID 8940179
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
Transcripts
ENST00000353533 ENSP00000262445
ENST00000415385 ENSP00000410402
ENST00000538465 ENSP00000467239
ENST00000536413
ENST00000582183 ENSP00000463507
ENST00000585076
ENST00000582897
ENST00000579089
ENST00000581941
ENST00000582377
ENST00000602811 ENSP00000473582
ENST00000602375 ENSP00000473472
ENST00000602305 ENSP00000473606
ENST00000602686 ENSP00000473458
ENST00000602537 ENSP00000473511
Interactions
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]
RNA-RNA 0
DNA-RNA 0
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
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
ENSMUSG00000033352
View Gene Order
ENSBTAG00000012103
Not yet available
Pathways
NETPATH
NetPath_8
Wnt pathway
NetPath_9
TNFalpha pathway
NetPath_13
IL1 pathway
NetPath_18
IL6 pathway
REACTOME
REACT_21368
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6788
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_8005
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_8006
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_25024
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_25222
MyD88 dependent cascade initiated on endosome pathway
REACT_9047
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_27215
MyD88 cascade initiated on plasma membrane pathway
REACT_9027
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_9061
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_22442
Interleukin-1 signaling pathway
REACT_120956
Cellular responses to stress pathway
REACT_9020
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_75790
Cytokine Signaling in Immune system pathway
REACT_6802
Innate Immune System pathway
REACT_228211
Uptake and actions of bacterial toxins pathway
REACT_7980
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_163936
Fc epsilon receptor (FCERI) signaling pathway
REACT_21308
MAP kinase activation in TLR cascade pathway
REACT_6900
Immune System pathway
REACT_169274
Cellular Senescence pathway
REACT_22232
Signaling by Interleukins pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_169436
Oxidative Stress Induced Senescence pathway
REACT_228255
Uptake and function of anthrax toxins pathway
REACT_116125
Disease pathway
REACT_163701
FCERI mediated MAPK activation pathway
KEGG
hsa04912
GnRH signaling pathway pathway
hsa04664
Fc epsilon RI signaling pathway pathway
hsa05120
Epithelial cell signaling in Helicobacter pylori infection pathway
hsa04012
ErbB signaling pathway pathway
hsa04010
MAPK signaling pathway pathway
hsa04620
Toll-like receptor signaling pathway pathway
hsa05142
Chagas disease (American trypanosomiasis) pathway
INOH
INOH website
IL-7 signaling pathway
INOH website
IL-1 signaling pathway pathway
INOH website
Toll-like receptor signaling pathway pathway
INOH website
JAK STAT pathway and regulation pathway
INOH website
EPO signaling pathway pathway
INOH website
VEGF signaling pathway pathway
INOH website
EGF signaling pathway pathway
INOH website
TNFR1 signaling pathway pathway
INOH website
Fas signaling pathway pathway
INOH website
TGF-beta signaling pathway
INOH website
PDGF signaling pathway pathway
PID NCI
nephrin_neph1_pathway
Nephrin/Neph1 signaling in the kidney podocyte
cd40_pathway
CD40/CD40L signaling
ceramide_pathway
Ceramide signaling pathway
met_pathway
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
anthraxpathway
Cellular roles of Anthrax toxin
lymphangiogenesis_pathway
VEGFR3 signaling in lymphatic endothelium
trail_pathway
TRAIL signaling pathway
erbb1_downstream_pathway
ErbB1 downstream signaling
fak_pathway
Signaling events mediated by focal adhesion kinase
rac1_pathway
RAC1 signaling pathway
ephrinbrevpathway
Ephrin B reverse signaling
tcrjnkpathway
JNK signaling in the CD4+ TCR pathway
cdc42_pathway
CDC42 signaling events
p38alphabetapathway
Regulation of p38-alpha and p38-beta
rhoa_pathway
RhoA signaling pathway
ar_tf_pathway
Regulation of Androgen receptor activity
fcer1pathway
Fc-epsilon receptor I signaling in mast cells
il6_7pathway
IL6-mediated signaling events
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
RefSeq NM_001281435 NM_003010 XM_005256753 XM_005256755 XM_006721568
HUGO
OMIM
CCDS CCDS11162 CCDS62095
HPRD
IMGT
EMBL
GenPept
RNA Seq Atlas

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca