MAP3K2

Mitogen-activated protein kinase kinase kinase 2
PDB rendering based on 2cu1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2CU1​, 2NPT​
Identifiers
Symbols	MAP3K2 ; MEKK2; MEKK2B
External IDs	OMIM: 609487 MGI: 1346873 HomoloGene: 74576 ChEMBL: 5914 GeneCards: MAP3K2 Gene
EC number	2.7.11.25
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • MAP kinase kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding • protein kinase binding • metal ion binding Cellular component • intracellular • nucleoplasm • cytoplasm • cytosol Biological process • activation of MAPKK activity • activation of MAPK activity • protein phosphorylation • activation of JUN kinase activity • positive regulation of transcription, DNA-templated • cellular response to mechanical stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10746	26405
Ensembl	ENSG00000169967	ENSMUSG00000024383
UniProt	Q9Y2U5	Q61083
RefSeq (mRNA)	NM_006609	NM_011946
RefSeq (protein)	NP_006600	NP_036076
Location (UCSC)	Chr 2: 127.3 – 127.39 Mb	Chr 18: 32.16 – 32.24 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP3K2 gene.^[1][2][3]

Function

The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate IkappaB kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process.^[3]

Interactions

MAP3K2 has been shown to interact with:

• MAP2K5,^[4]
• MAP2K7,^[5]
• MAPK8,^[5]
• SH2D2A,^[4] and
• XIAP^[6]

References

1. Blank JL, Gerwins P, Elliott EM, Sather S, Johnson GL (Mar 1996). "Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase". The Journal of Biological Chemistry 271 (10): 5361–8. doi:10.1074/jbc.271.10.5361. PMID 8621389.
2. Zhao Q, Lee FS (Mar 1999). "Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta". The Journal of Biological Chemistry 274 (13): 8355–8. doi:10.1074/jbc.274.13.8355. PMID 10085062.
3. "Entrez Gene: MAP3K2 mitogen-activated protein kinase kinase kinase 2".
4. Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW, Johnson GL (Feb 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry 276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID 11073940.
5. Cheng J, Yang J, Xia Y, Karin M, Su B (Apr 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Molecular and Cellular Biology 20 (7): 2334–42. doi:10.1128/mcb.20.7.2334-2342.2000. PMC 85399. PMID 10713157.
6. Winsauer G, Resch U, Hofer-Warbinek R, Schichl YM, de Martin R (Nov 2008). "XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2". Cellular Signalling 20 (11): 2107–12. doi:10.1016/j.cellsig.2008.08.004. PMID 18761086.

Further reading

• Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ (1995). "Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1". Nature 372 (6508): 798–800. doi:10.1038/372798a0. PMID 7997270.
• Wu Z, Wu J, Jacinto E, Karin M (Dec 1997). "Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase". Molecular and Cellular Biology 17 (12): 7407–16. doi:10.1128/mcb.17.12.7407. PMC 232596. PMID 9372971.
• Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR (Feb 1998). "14-3-3 proteins interact with specific MEK kinases". The Journal of Biological Chemistry 273 (6): 3476–83. doi:10.1074/jbc.273.6.3476. PMID 9452471.
• Cheng J, Yang J, Xia Y, Karin M, Su B (Apr 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Molecular and Cellular Biology 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. PMC 85399. PMID 10713157.
• Sun W, Vincent S, Settleman J, Johnson GL (Aug 2000). "MEK kinase 2 binds and activates protein kinase C-related kinase 2. Bifurcation of kinase regulatory pathways at the level of an MAPK kinase kinase". The Journal of Biological Chemistry 275 (32): 24421–8. doi:10.1074/jbc.M003148200. PMID 10818102.
• Garrington TP, Ishizuka T, Papst PJ, Chayama K, Webb S, Yujiri T, Sun W, Sather S, Russell DM, Gibson SB, Keller G, Gelfand EW, Johnson GL (Oct 2000). "MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells". The EMBO Journal 19 (20): 5387–95. doi:10.1093/emboj/19.20.5387. PMC 314024. PMID 11032806.
• Huang J, Tu Z, Lee FS (Apr 2003). "Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity". Biochemical and Biophysical Research Communications 303 (2): 532–40. doi:10.1016/S0006-291X(03)00387-5. PMID 12659851.
• Nakamura K, Johnson GL (Sep 2003). "PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway". The Journal of Biological Chemistry 278 (39): 36989–92. doi:10.1074/jbc.C300313200. PMID 12912994.
• Hammaker DR, Boyle DL, Chabaud-Riou M, Firestein GS (Feb 2004). "Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis". Journal of Immunology 172 (3): 1612–8. doi:10.4049/jimmunol.172.3.1612. PMID 14734742.
• Raviv Z, Kalie E, Seger R (Apr 2004). "MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation". Journal of Cell Science 117 (Pt 9): 1773–84. doi:10.1242/jcs.01040. PMID 15075238.
• Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (Aug 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Benzinger A, Muster N, Koch HB, Yates JR, Hermeking H (Jun 2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Molecular & Cellular Proteomics 4 (6): 785–95. doi:10.1074/mcp.M500021-MCP200. PMID 15778465.
• Cheng J, Zhang D, Kim K, Zhao Y, Zhao Y, Su B (Jul 2005). "Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation". Molecular and Cellular Biology 25 (14): 5955–64. doi:10.1128/MCB.25.14.5955-5964.2005. PMC 1168836. PMID 15988011.
• Pelkmans L, Zerial M (Jul 2005). "Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae". Nature 436 (7047): 128–33. doi:10.1038/nature03866. PMID 16001074.
• Wissing J, Jänsch L, Nimtz M, Dieterich G, Hornberger R, Kéri G, Wehland J, Daub H (Mar 2007). "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Molecular & Cellular Proteomics 6 (3): 537–47. doi:10.1074/mcp.T600062-MCP200. PMID 17192257.