MAP3K1

Mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase

Identifiers

MAP3K1 ; MAPKKK1; MEKK; MEKK 1; MEKK1; SRXY6

External IDs

OMIM: 600982 MGI: 1346872 HomoloGene: 8056 ChEMBL: 3956 GeneCards: MAP3K1 Gene

2.7.11.25

Gene ontology
Molecular function	• protein kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding • zinc ion binding • JUN kinase kinase activity • protein kinase binding
Cellular component	• cytoplasm • cytosol
Biological process	• activation of MAPKK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • epithelial cell morphogenesis • protein phosphorylation • transforming growth factor beta receptor signaling pathway • activation of JUN kinase activity • regulation of mitotic cell cycle • apoptotic mitochondrial changes • regulation of cell migration • positive regulation of actin filament polymerization • activation of protein kinase activity • toll-like receptor 2 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • Fc-epsilon receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • wound healing • regulation of apoptotic process • innate immune response • stress-activated MAPK cascade • eyelid development in camera-type eye • cellular response to mechanical stimulus
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
56.82 – 56.9 Mb

Chr 13:
111.75 – 111.81 Mb

PubMed search

Mitogen-activated protein kinase kinase kinase 1 is an enzyme that in humans is encoded by the MAP3K1 gene.^[1]^[2]

Function

MAP3K, or MEK kinase, is a serine/threonine kinase that occupies a pivotal role in a network of phosphorylating enzymes integrating cellular responses to a number of mitogenic and metabolic stimuli, including insulin and many growth factors.^[2]

Mouse genetics has revealed that the kinase is important in: correct embryogenesis, keratinocyte migration, T cell cytokine production and B cell antibody production.

Interactions

MAP3K1 has been shown to interact with:

References

↑ Vinik BS, Kay ES, Fiedorek FT (Nov 1995). "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5". Mammalian Genome 6 (11): 782–3. doi:10.1007/BF00539003. PMID 8597633.
1 2 "Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1".
↑ Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". The Journal of Biological Chemistry 277 (20): 17706–12. doi:10.1074/jbc.M111982200. PMID 11884395.
↑ Zhang Y, Neo SY, Han J, Lin SC (Aug 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". The Journal of Biological Chemistry 275 (32): 25008–14. doi:10.1074/jbc.M002491200. PMID 10829020.
1 2 3 Karandikar M, Xu S, Cobb MH (Dec 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". The Journal of Biological Chemistry 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.
↑ Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F (Sep 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". The Journal of Biological Chemistry 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. PMID 9733714.
↑ Xu S, Cobb MH (Dec 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". The Journal of Biological Chemistry 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID 9405400.
↑ Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (May 1999). "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain". Genes & Development 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. PMC 316725. PMID 10346818.
↑ Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (Apr 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Letters 425 (3): 431–5. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508.

Lee FS, Hagler J, Chen ZJ, Maniatis T (Jan 1997). "Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway". Cell 88 (2): 213–22. doi:10.1016/S0092-8674(00)81842-5. PMID 9008162.
Siow YL, Kalmar GB, Sanghera JS, Tai G, Oh SS, Pelech SL (Mar 1997). "Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C". The Journal of Biological Chemistry 272 (12): 7586–94. doi:10.1074/jbc.272.12.7586. PMID 9065412.
Su YC, Han J, Xu S, Cobb M, Skolnik EY (Mar 1997). "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain". The EMBO Journal 16 (6): 1279–90. doi:10.1093/emboj/16.6.1279. PMC 1169726. PMID 9135144.
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.
Xu S, Cobb MH (Dec 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". The Journal of Biological Chemistry 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID 9405400.
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.
Hirai S, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, Fukuyama K, Ohno S (Mar 1998). "Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2". The Journal of Biological Chemistry 273 (13): 7406–12. doi:10.1074/jbc.273.13.7406. PMID 9516438.
Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (Apr 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Letters 425 (3): 431–5. doi:10.1016/S0014-5793(98)00287-7. PMID 9563508.
Guan Z, Buckman SY, Pentland AP, Templeton DJ, Morrison AR (May 1998). "Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway". The Journal of Biological Chemistry 273 (21): 12901–8. doi:10.1074/jbc.273.21.12901. PMID 9582321.
Lee FS, Peters RT, Dang LC, Maniatis T (Aug 1998). "MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta". Proceedings of the National Academy of Sciences of the United States of America 95 (16): 9319–24. doi:10.1073/pnas.95.16.9319. PMC 21336. PMID 9689078.
Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (Aug 1998). "Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38". The Journal of Biological Chemistry 273 (35): 22681–92. doi:10.1074/jbc.273.35.22681. PMID 9712898.
Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F (Sep 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". The Journal of Biological Chemistry 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. PMID 9733714.
Xia Y, Wu Z, Su B, Murray B, Karin M (Nov 1998). "JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension". Genes & Development 12 (21): 3369–81. doi:10.1101/gad.12.21.3369. PMC 317229. PMID 9808624.
Nemoto S, DiDonato JA, Lin A (Dec 1998). "Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase". Molecular and Cellular Biology 18 (12): 7336–43. doi:10.1128/mcb.18.12.7336. PMC 109315. PMID 9819420.
Yujiri T, Sather S, Fanger GR, Johnson GL (Dec 1998). "Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption". Science 282 (5395): 1911–4. doi:10.1126/science.282.5395.1911. PMID 9836645.
Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (May 1999). "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain". Genes & Development 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. PMC 316725. PMID 10346818.
Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway CA, Ghosh S (Aug 1999). "ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway". Genes & Development 13 (16): 2059–71. doi:10.1101/gad.13.16.2059. PMC 316957. PMID 10465784.
Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI (Nov 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Molecular and Cellular Biology 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. PMC 84763. PMID 10523642.
Minamino T, Yujiri T, Papst PJ, Chan ED, Johnson GL, Terada N (Dec 1999). "MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes". Proceedings of the National Academy of Sciences of the United States of America 96 (26): 15127–32. doi:10.1073/pnas.96.26.15127. PMC 24784. PMID 10611349.

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)) (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

Proteins: 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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MAP3K1

Function

Interactions

References

Further reading