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Mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
External IDs OMIM600982 MGI1346872 HomoloGene8056 IUPHAR: 2069 ChEMBL: 3956 GeneCards: MAP3K1 Gene
EC number
RNA expression pattern
PBB GE MAP3K1 214786 at tn.png
More reference expression data
Species Human Mouse
Entrez 4214 26401
Ensembl ENSG00000095015 ENSMUSG00000021754
UniProt Q13233 P53349
RefSeq (mRNA) NM_005921 NM_011945
RefSeq (protein) NP_005912 NP_036075
Location (UCSC) Chr 5:
56.11 – 56.19 Mb
Chr 13:
111.75 – 111.81 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 1 is an enzyme that in humans is encoded by the MAP3K1 gene.[1][2]

MAP3K, or MEK kinase, is a serine/threonine kinase that occupies a pivotal role in a network of phosphorylating enzymes integrating cellular responses to a number of mitogenic and metabolic stimuli, including insulin (MIM 176730) and many growth factors.[supplied by OMIM][2]

Mouse genetics has revealed that the kinase is important in: correct embryogenesis, keratinocyte migration, T cell cytokine production and B cell antibody production.


MAP3K1 has been shown to interact with C-Raf,[3] MAPK8,[4] TRAF2,[5] MAP2K1,[3] Grb2,[6] MAPK1,[3] AXIN1[7][8] and UBE2I.[9]


  1. ^ Vinik BS, Kay ES, Fiedorek FT Jr (April 1996). "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5". Mamm Genome 6 (11): 782–3. doi:10.1007/BF00539003. PMID 8597633. 
  2. ^ a b "Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1". 
  3. ^ a b c Karandikar, M; Xu S; Cobb M H (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. doi:10.1074/jbc.M005926200. ISSN 0021-9258. PMID 10969079. 
  4. ^ Xu, S; Cobb M H (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. (UNITED STATES) 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. ISSN 0021-9258. PMID 9405400. 
  5. ^ Baud, V; Liu Z G; Bennett B; Suzuki N; Xia Y; Karin M (May 1999). "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain". Genes Dev. (UNITED STATES) 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. ISSN 0890-9369. PMC 316725. PMID 10346818. 
  6. ^ Pomérance, M; Multon M C; Parker F; Venot C; Blondeau J P; Tocqué B; Schweighoffer F (September 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun–kinase activities in response to epidermal growth factor". J. Biol. Chem. (UNITED STATES) 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. ISSN 0021-9258. PMID 9733714. 
  7. ^ Zhang, Yi; Qiu Wen-Jie; Chan Siu Chiu; Han Jiahuai; He Xi; Lin Sheng-Cai (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". J. Biol. Chem. (United States) 277 (20): 17706–12. doi:10.1074/jbc.M111982200. ISSN 0021-9258. PMID 11884395. 
  8. ^ Zhang, Y; Neo S Y; Han J; Lin S C (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. (UNITED STATES) 275 (32): 25008–14. doi:10.1074/jbc.M002491200. ISSN 0021-9258. PMID 10829020. 
  9. ^ Saltzman, A; Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Lett. (NETHERLANDS) 425 (3): 431–5. doi:10.1016/S0014-5793(98)00287-7. ISSN 0014-5793. PMID 9563508. 

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