MAP3K2

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2CU1, 2NPT, 5EX0, 5HQ8

Identifiers

Aliases

MAP3K2, MEKK2, MEKK2B, mitogen-activated protein kinase kinase kinase 2

External IDs

MGI: 1346873 HomoloGene: 74576 GeneCards: MAP3K2

Gene ontology
Molecular function	• nucleotide binding • protein binding • protein kinase binding • kinase activity • ATP binding • protein serine/threonine kinase activity • transferase activity • MAP kinase kinase kinase activity • metal ion binding • protein kinase activity • signal transducer, downstream of receptor, with serine/threonine kinase activity
Cellular component	• nucleus • nucleoplasm • cytosol • cytoplasm
Biological process	• phosphorylation • positive regulation of transcription, DNA-templated • activation of MAPK activity • cellular response to mechanical stimulus • protein phosphorylation • activation of JUN kinase activity • activation of MAPKK activity
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_006600.3


n/a

Location (UCSC)

Chr 2: 127.3 – 127.39 Mb

Chr 18: 32.16 – 32.24 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

Mitogen-activated protein kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP3K2 gene.^[3]^[4]^[5]

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.^[5]

Interactions

MAP3K2 has been shown to interact with:

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
↑ 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.
1 2 "Entrez Gene: MAP3K2 mitogen-activated protein kinase kinase kinase 2".
1 2 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.
1 2 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.
↑ 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.

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.

PDB gallery

2cu1: Solution structure of the PB1 domain of human protein kinase MEKK2b

2npt: Crystal Structure of the complex of human mitogen activated protein kinase kinase 5 phox domain (MAP2K5-phox) with human mitogen activated protein kinase kinase kinase 2 phox domain (MAP3K2-phox)

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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MAP3K2

Function

Interactions

References

Further reading