MAP2K4

MAP2K4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3ALN, 3ALO, 3VUT
Identifiers
Aliases	MAP2K4, JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDs	OMIM: 601335; MGI: 1346869; HomoloGene: 48159; GeneCards: MAP2K4; OMA:MAP2K4 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p12 Start 12,020,829 bp[1] End 12,143,830 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B3|11 40.53 cM Start 65,579,069 bp[2] End 65,679,123 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus Brodmann area 46 postcentral gyrus orbitofrontal cortex pars compacta middle temporal gyrus superior frontal gyrus prefrontal cortex Achilles tendon Brodmann area 23 Top expressed in dentate gyrus of hippocampal formation granule cell genital tubercle facial motor nucleus superior frontal gyrus primary visual cortex anterior horn of spinal cord secondary oocyte dorsomedial hypothalamic nucleus granulocyte paraventricular nucleus of hypothalamus More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding kinase activity protein binding protein tyrosine kinase activity ATP binding MAP kinase kinase activity JUN kinase kinase activity protein serine/threonine kinase activity mitogen-activated protein kinase kinase kinase binding Cellular component cytoplasm nucleus dendrite cytoplasm cytosol perikaryon axon Biological process phosphorylation MAPK cascade protein phosphorylation cellular response to mechanical stimulus response to wounding peptidyl-tyrosine phosphorylation signal transduction negative regulation of motor neuron apoptotic process apoptotic process cell growth involved in cardiac muscle cell development cellular response to sorbitol positive regulation of smooth muscle cell apoptotic process JNK cascade positive regulation of protein phosphorylation positive regulation of neuron apoptotic process positive regulation of DNA replication positive regulation of apoptotic process positive regulation of nitric-oxide synthase biosynthetic process regulation of mitotic cell cycle stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process Fc-epsilon receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6416 26398 Ensembl ENSG00000065559 ENSMUSG00000033352 UniProt P45985 P47809 RefSeq (mRNA) NM_001281435 NM_003010 NM_009157 NM_001316367 NM_001316368 NM_001316369 NM_001362739 NM_001362740 RefSeq (protein) NP_001268364 NP_003001 NP_001303296 NP_001303297 NP_001303298 NP_033183 NP_001349668 NP_001349669 Location (UCSC) Chr 17: 12.02 – 12.14 Mb Chr 11: 65.58 – 65.68 Mb PubMed search [3] [4]
Wikidata
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Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.^[5]

MAP2K4 encodes a dual-specificity kinase that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains a kinase domain that is phosphorylated and activated by MAP3K1(aka MEKK1).^[6] MAP2K4 contains multiple amino acid sites that are phosphorylated and ubiquitinated.^[7] Genetic studies using Map2k4 knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation.^[8][9] Analysis of chimeric mice identified a role for Map2k4 in T cell cytokine production and proliferation.^[10] Map2k4-deficient chimeric mice frequently develop lymphadenopathy.^[11] MAP2K4 is altered in 1.97% of all human cancers.^[12]

MAP2K4 has been shown to interact with:

• MAP3K1,^[13]
• FLNC,^[14]
• MAPK8,^{[15][16][17][18][19]}
• MAPK8IP3^[20][21] and
• AKT1.^[16]
• ITCH.^[22]