MAP3K8

Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene.^[5][6][7]

MAP3K8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4Y83, 4Y85
Identifiers
Aliases	MAP3K8, COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT, AURA2, mitogen-activated protein kinase kinase kinase 8, Tpl2
External IDs	OMIM: 191195; MGI: 1346878; HomoloGene: 3812; GeneCards: MAP3K8; OMA:MAP3K8 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p11.23 Start 30,434,021 bp[1] End 30,461,833 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 A1|18 2.73 cM Start 4,331,327 bp[2] End 4,353,015 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa mucosa of paranasal sinus upper lobe of left lung left uterine tube germinal epithelium monocyte olfactory zone of nasal mucosa Achilles tendon tibial nerve right lung Top expressed in granulocyte saccule lip otic placode skin of external ear stroma of bone marrow spleen otic vesicle hair follicle subcutaneous adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity metal ion binding kinase activity protein binding ATP binding magnesium ion binding MAP kinase kinase kinase activity protein serine/threonine kinase activity Cellular component cytosol cytoplasm Biological process phosphorylation immune system process T cell costimulation stress-activated MAPK cascade cell cycle signal transduction protein phosphorylation regulation of mitotic cell cycle stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process interleukin-1-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1326 26410 Ensembl ENSG00000107968 ENSMUSG00000024235 UniProt P41279 Q07174 RefSeq (mRNA) NM_001244134 NM_005204 NM_001320961 NM_007746 RefSeq (protein) NP_001231063 NP_001307890 NP_005195 NP_031772 Location (UCSC) Chr 10: 30.43 – 30.46 Mb Chr 18: 4.33 – 4.35 Mb PubMed search [3] [4]
Wikidata
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Function

The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases.^[8][9] This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity.^[7] In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer.^[10] However, it functions in other organs as a oncogene, promoting cancer.^[11]

Interactions

MAP3K8 has been shown to interact with AKT1,^[12] CHUK,^[13] NFKB2,^[14] NFKB1,^[14][15] C22orf25^[16] and TNIP2.^[17]