MAP4K4

Mitogen-activated protein kinase kinase kinase kinase 4

Identifiers

MAP4K4; FLH21957; FLJ10410; FLJ20373; FLJ90111; HGK; KIAA0687; MEKKK4; NIK

External IDs

OMIM: 604666 MGI: 1349394 HomoloGene: 7442 GeneCards: MAP4K4 Gene

2.7.11.1

Gene Ontology
Molecular function	• nucleotide binding • protein serine/threonine kinase activity • small GTPase regulator activity • protein binding • ATP binding
Cellular component	• cytoplasm
Biological process	• protein phosphorylation • response to stress • intracellular protein kinase cascade • regulation of JNK cascade
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
102.31 – 102.51 Mb

Chr 1:
39.96 – 40.08 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.^[1]^[2]^[3]^[4]

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.^[4]

Interactions

MAP4K4 has been shown to interact with NCK1^[3] and CD29.^[5]

References

^ 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.
^ 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.
^ ^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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169726.
^ ^a ^b "Entrez Gene: MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9448.
^ 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.

Becker E, Huynh-Do U, Holland S, et al. (2000). "Nck-Interacting Ste20 Kinase Couples Eph Receptors to c-Jun N-Terminal Kinase and Integrin Activation". Mol. Cell. Biol. 20 (5): 1537–45. doi:10.1128/MCB.20.5.1537-1545.2000. PMC 85333. PMID 10669731. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85333.
Zhao ZS, Manser E, Lim L (2000). "Interaction between PAK and Nck: a Template for Nck Targets and Role of PAK Autophosphorylation". Mol. Cell. Biol. 20 (11): 3906–17. doi:10.1128/MCB.20.11.3906-3917.2000. PMC 85736. PMID 10805734. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85736.
Hofer-Warbinek R, Schmid JA, Stehlik C, et al. (2000). "Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1". J. Biol. Chem. 275 (29): 22064–8. doi:10.1074/jbc.M910346199. PMID 10807933.
Chaudhary PM, Eby MT, Jasmin A, et al. (2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene 19 (39): 4451–60. doi:10.1038/sj.onc.1203812. PMID 11002417.
Yan W, Nehrke K, Choi J, Barber DL (2001). "The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor". J. Biol. Chem. 276 (33): 31349–56. doi:10.1074/jbc.M102679200. PMID 11369779.
Poinat P, De Arcangelis A, Sookhareea S, et al. (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. 12 (8): 622–31. doi:10.1016/S0960-9822(02)00764-9. PMID 11967148.
Fong A, Zhang M, Neely J, Sun SC (2002). "S9, a 19 S proteasome subunit interacting with ubiquitinated NF-kappaB2/p100". J. Biol. Chem. 277 (43): 40697–702. doi:10.1074/jbc.M205330200. PMID 12185077.
Luan Z, Zhang Y, Liu A, et al. (2002). "A novel GTP-binding protein hGBP3 interacts with NIK/HGK". FEBS Lett. 530 (1–3): 233–8. doi:10.1016/S0014-5793(02)03467-1. PMID 12387898.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Wright JH, Wang X, Manning G, et al. (2003). "The STE20 Kinase HGK Is Broadly Expressed in Human Tumor Cells and Can Modulate Cellular Transformation, Invasion, and Adhesion". Mol. Cell. Biol. 23 (6): 2068–82. doi:10.1128/MCB.23.6.2068-2082.2003. PMC 149462. PMID 12612079. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149462.
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200. PMID 14578343.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Machida N, Umikawa M, Takei K, et al. (2004). "Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase". J. Biol. Chem. 279 (16): 15711–4. doi:10.1074/jbc.C300542200. PMID 14966141.
Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446.
Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
Collins CS, Hong J, Sapinoso L, et al. (2006). "A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase". Proc. Natl. Acad. Sci. U.S.A. 103 (10): 3775–80. doi:10.1073/pnas.0600040103. PMC 1383649. PMID 16537454. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1383649.
Wissing J, Jänsch L, Nimtz M, et al. (2007). "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Mol. Cell Proteomics 6 (3): 537–47. doi:10.1074/mcp.T600062-MCP200. PMID 17192257.

MAP4K4

Interactions

References

Further reading