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Mitogen-activated protein kinase kinase kinase kinase 4
Crystal Structure of MAP4K4. PDB entry 4obo[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MAP4K4 ; FLH21957; HEL-S-31; HGK; MEKKK4; NIK
External IDs OMIM604666 MGI1349394 HomoloGene7442 IUPHAR: 2088 ChEMBL: 6166 GeneCards: MAP4K4 Gene
EC number
RNA expression pattern
PBB GE MAP4K4 206571 s at tn.png
PBB GE MAP4K4 218181 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9448 26921
Ensembl ENSG00000071054 ENSMUSG00000026074
UniProt O95819 P97820
RefSeq (mRNA) NM_001242559 NM_001252200
RefSeq (protein) NP_001229488 NP_001239129
Location (UCSC) Chr 2:
102.31 – 102.51 Mb
Chr 1:
39.9 – 40.03 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase kinase 4 is an enzyme that in humans is encoded by the MAP4K4 gene.[2][3][4][5]

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified.[5]


MAP4K4 has been shown to interact with NCK1[4] and CD29.[6]


  1. ^ Crawford, T. D.; Ndubaku, C. O.; Chen, H; Boggs, J. W.; Bravo, B. J.; Delatorre, K; Giannetti, A. M.; Gould, S. E.; Harris, S. F.; Magnuson, S. R.; McNamara, E; Murray, L. J.; Nonomiya, J; Sambrone, A; Schmidt, S; Smyczek, T; Stanley, M; Vitorino, P; Wang, L; West, K; Wu, P; Ye, W (2014). "Discovery of Selective 4-Amino-pyridopyrimidine Inhibitors of MAP4K4 Using Fragment-Based Lead Identification and Optimization". Journal of Medicinal Chemistry 57 (8): 3484–93. doi:10.1021/jm500155b. PMID 24673130.  edit
  2. ^ Yao Z, Zhou G, Wang XS, Brown A, Diener K, Gan H, Tan TH (Feb 1999). "A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway". J Biol Chem 274 (4): 2118–25. doi:10.1074/jbc.274.4.2118. PMID 9890973. 
  3. ^ Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Dec 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res 5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID 9734811. 
  4. ^ a b Su YC, Han J, Xu S, Cobb M, Skolnik EY (May 1997). "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain". EMBO J 16 (6): 1279–90. doi:10.1093/emboj/16.6.1279. PMC 1169726. PMID 9135144. 
  5. ^ a b "Entrez Gene: MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4". 
  6. ^ Poinat, Patrice; De Arcangelis Adèle, Sookhareea Satis, Zhu Xiaoping, Hedgecock Edward M, Labouesse Michel, Georges-Labouesse Elisabeth (Apr 2002). "A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans". Curr. Biol. (England) 12 (8): 622–31. doi:10.1016/S0960-9822(02)00764-9. ISSN 0960-9822. PMID 11967148. 

Further reading[edit]