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MAP3K2

MAP3K2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAP3K2, MEKK2, MEKK2B, mitogen-activated protein kinase kinase kinase 2
External IDsOMIM: 609487; MGI: 1346873; HomoloGene: 74576; GeneCards: MAP3K2; OMA:MAP3K2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10746

26405

Ensembl

ENSG00000169967

ENSMUSG00000024383

UniProt

Q9Y2U5

Q61083

RefSeq (mRNA)

NM_006609
NM_001371910
NM_001371911

NM_011946

RefSeq (protein)

NP_006600
NP_001358839
NP_001358840

NP_036076

Location (UCSC)Chr 2: 127.3 – 127.39 MbChr 18: 32.3 – 32.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 (MEK/ERK Kinase 2) is an enzyme that in humans is encoded by the MAP3K2 gene.[5][6][7]

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.[7]

Activation

MEKK2 is activated through homodimerization and subsequent trans-autophosphorylation at MEKK2-S519.[8][9]

MEKK2 is regulated by 14-3-3 proteins which bind to MEKK2-phosphoT283.[10]

MEKK2 is regulated by SMYD3 which binds and methylates MEKK2-K260.[11]

Interactions

MAP3K2 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000169967 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024383 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b "Entrez Gene: MAP3K2 mitogen-activated protein kinase kinase kinase 2".
  8. ^ Cheng J, Yu L, Zhang D, Huang Q, Spencer D, Su B (2005-04-08). "Dimerization through the Catalytic Domain Is Essential for MEKK2 Activation". Journal of Biological Chemistry. 280 (14): 13477–13482. doi:10.1074/jbc.M414258200. ISSN 0021-9258. PMID 15695508.
  9. ^ Zhang D, Facchinetti V, Wang X, Huang Q, Qin J, Su B (2006-01-11). "Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways". The EMBO Journal. 25 (1): 97–107. doi:10.1038/sj.emboj.7600913. ISSN 0261-4189. PMC 1356356. PMID 16362041.
  10. ^ Matitau AE, Gabor TV, Gill RM, Scheid MP (2013-09-27). "MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N-terminal kinase". The Journal of Biological Chemistry. 288 (39): 28293–28302. doi:10.1074/jbc.M113.511352. ISSN 1083-351X. PMC 3784737. PMID 23963453.
  11. ^ a b Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, Van Aller GS, Huddleston M, Dhanak D, Tummino PJ (June 2014). "SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer". Nature. 510 (7504): 283–287. Bibcode:2014Natur.510..283M. doi:10.1038/nature13320. ISSN 1476-4687. PMC 4122675. PMID 24847881.
  12. ^ a b 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.
  13. ^ Deacon K, Blank JL (1997-05-30). "Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo". The Journal of Biological Chemistry. 272 (22): 14489–14496. doi:10.1074/jbc.272.22.14489. ISSN 0021-9258. PMID 9162092.
  14. ^ a b 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.
  15. ^ Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR (1998-02-06). "14-3-3 Proteins Interact with Specific MEK Kinases". Journal of Biological Chemistry. 273 (6): 3476–3483. doi:10.1074/jbc.273.6.3476. ISSN 0021-9258. PMID 9452471.
  16. ^ 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.

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