MAPK6

Mitogen-activated protein kinase 6

PDB rendering based on 2i6l.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2I6L

Identifiers

Symbols

MAPK6 ; ERK3; HsT17250; PRKM6; p97MAPK

External IDs

OMIM: 602904 MGI: 1354946 HomoloGene: 55683 ChEMBL: 5121 GeneCards: MAPK6 Gene

EC number

2.7.11.24

Gene ontology
Molecular function	• protein serine/threonine kinase activity • MAP kinase activity • protein binding • ATP binding • protein kinase binding • protein heterodimerization activity
Cellular component	• nucleus • cytoplasm
Biological process	• MAPK cascade • protein phosphorylation • cell cycle • signal transduction
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 15:
51.95 – 52.07 Mb

Chr 9:
75.37 – 75.41 Mb

PubMed search

Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.^[1]^[2]

The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters.^[2]

References

↑ Meloche S, Beatty BG, Pellerin J (Dec 1996). "Primary structure, expression and chromosomal locus of a human homolog of rat ERK3". Oncogene 13 (7): 1575–9. PMID 8875998.
1 2 "Entrez Gene: MAPK6 mitogen-activated protein kinase 6".

External links

MAP Kinase Resource .

Boulton TG, Nye SH, Robbins DJ, et al. (1991). "ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF". Cell 65 (4): 663–675. doi:10.1016/0092-8674(91)90098-J. PMID 2032290.
Zhu AX, Zhao Y, Moller DE, Flier JS (1994). "Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3". Mol. Cell. Biol. 14 (12): 8202–11. PMC 359359. PMID 7969157.
Cheng M, Boulton TG, Cobb MH (1996). "ERK3 is a constitutively nuclear protein kinase". J. Biol. Chem. 271 (15): 8951–8958. doi:10.1074/jbc.271.15.8951. PMID 8621539.
Sauma S, Friedman E (1996). "Increased expression of protein kinase C beta activates ERK3". J. Biol. Chem. 271 (19): 11422–11426. doi:10.1074/jbc.271.19.11422. PMID 8626698.
Zimmermann J, Lamerant N, Grossenbacher R, Furst P (2001). "Proteasome- and p38-dependent regulation of ERK3 expression". J. Biol. Chem. 276 (14): 10759–10766. doi:10.1074/jbc.M008567200. PMID 11148204.
Robinson MJ, Xu Be BE, Stippec S, Cobb MH (2002). "Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo". J. Biol. Chem. 277 (7): 5094–5100. doi:10.1074/jbc.M110935200. PMID 11741894.
Kinet S, Bernard F, Mongellaz C, et al. (2002). "gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes". Blood 100 (7): 2546–2553. doi:10.1182/blood-2002-03-0819. PMID 12239168.
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): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Coulombe P, Rodier G, Pelletier S, et al. (2003). "Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation". Mol. Cell. Biol. 23 (13): 4542–4558. doi:10.1128/MCB.23.13.4542-4558.2003. PMC 164847. PMID 12808096.
Julien C, Coulombe P, Meloche S (2004). "Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression". J. Biol. Chem. 278 (43): 42615–42624. doi:10.1074/jbc.M302724200. PMID 12915405.
Rai R, Mahale A, Saranath D (2004). "Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma". Oral Oncol. 40 (7): 705–712. doi:10.1016/j.oraloncology.2004.01.010. PMID 15172640.
Coulombe P, Rodier G, Bonneil E, et al. (2004). "N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome". Mol. Cell. Biol. 24 (14): 6140–6150. doi:10.1128/MCB.24.14.6140-6150.2004. PMC 434260. PMID 15226418.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514.
Hoeflich KP, Eby MT, Forrest WF, et al. (2006). "Regulation of ERK3/MAPK6 expression by BRAF". Int. J. Oncol. 29 (4): 839–49. doi:10.3892/ijo.29.4.839. PMID 16964379.

PDB gallery

2i6l: Crystal structure of human mitogen activated protein kinase 6 (MAPK6)

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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MAPK6

References

External links

Further reading