MKNK1

MAP kinase interacting serine/threonine kinase 1

PDB rendering based on 2hw6.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2HW6, 2Y9Q

Identifiers

Symbols

MKNK1 ; MNK1

External IDs

OMIM: 606724 MGI: 894316 HomoloGene: 37838 IUPHAR: 2104 ChEMBL: 4718 GeneCards: MKNK1 Gene

EC number

2.7.11.1

Gene ontology
Molecular function	• protein serine/threonine kinase activity • protein binding • ATP binding
Cellular component	• nucleus • cytosol
Biological process	• regulation of translation • protein phosphorylation • fibroblast growth factor receptor signaling pathway • response to salt stress • peptidyl-serine phosphorylation • intracellular signal transduction • extrinsic apoptotic signaling pathway in absence of ligand
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
47.02 – 47.08 Mb

Chr 4:
115.84 – 115.88 Mb

PubMed search

MAP kinase-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MKNK1 gene.^[1]^[2]

Interactions

MKNK1 has been shown to interact with MAPK1^[3] and Eukaryotic translation initiation factor 4 gamma.^[4]

References

↑ Fukunaga R, Hunter T (Jun 1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
↑ "Entrez Gene: MKNK1 MAP kinase interacting serine/threonine kinase 1".
↑ Waskiewicz, A J; Flynn A; Proud C G; Cooper J A (Apr 1997). "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. (ENGLAND) 16 (8): 1909–20. doi:10.1093/emboj/16.8.1909. ISSN 0261-4189. PMC 1169794. PMID 9155017.
↑ Pyronnet, S; Imataka H; Gingras A C; Fukunaga R; Hunter T; Sonenberg N (Jan 1999). "Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E". EMBO J. (ENGLAND) 18 (1): 270–9. doi:10.1093/emboj/18.1.270. ISSN 0261-4189. PMC 1171121. PMID 9878069.

de Carvalho MG, McCormack AL, Olson E et al. (1996). "Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes.". J. Biol. Chem. 271 (12): 6987–97. doi:10.1074/jbc.271.12.6987. PMID 8636128.
Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (1997). "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2.". EMBO J. 16 (8): 1909–20. doi:10.1093/emboj/16.8.1909. PMC 1169794. PMID 9155017.
Börsch-Haubold AG, Bartoli F, Asselin J et al. (1998). "Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells.". J. Biol. Chem. 273 (8): 4449–58. doi:10.1074/jbc.273.8.4449. PMID 9468497.
Pyronnet S, Imataka H, Gingras AC et al. (1999). "Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E.". EMBO J. 18 (1): 270–9. doi:10.1093/emboj/18.1.270. PMC 1171121. PMID 9878069.
Waskiewicz AJ, Johnson JC, Penn B et al. (1999). "Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo.". Mol. Cell. Biol. 19 (3): 1871–80. PMC 83980. PMID 10022874.
Cuesta R, Laroia G, Schneider RJ (2000). "Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes.". Genes Dev. 14 (12): 1460–70. PMC 316692. PMID 10859165.
Hefner Y, Borsch-Haubold AG, Murakami M et al. (2001). "Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.". J. Biol. Chem. 275 (48): 37542–51. doi:10.1074/jbc.M003395200. PMID 10978317.
Scheper GC, Morrice NA, Kleijn M, Proud CG (2001). "The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells.". Mol. Cell. Biol. 21 (3): 743–54. doi:10.1128/MCB.21.3.743-754.2001. PMC 86666. PMID 11154262.
Knauf U, Tschopp C, Gram H (2001). "Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2.". Mol. Cell. Biol. 21 (16): 5500–11. doi:10.1128/MCB.21.16.5500-5511.2001. PMC 87272. PMID 11463832.
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): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Reuter TY, Medhurst AL, Waisfisz Q et al. (2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport.". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Cuesta R, Xi Q, Schneider RJ (2004). "Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein.". J. Virol. 78 (14): 7707–16. doi:10.1128/JVI.78.14.7707-7716.2004. PMC 434077. PMID 15220445.
Orton KC, Ling J, Waskiewicz AJ et al. (2004). "Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk.". J. Biol. Chem. 279 (37): 38649–57. doi:10.1074/jbc.M407337200. PMID 15234964.
O'Loghlen A, González VM, Piñeiro D et al. (2004). "Identification and molecular characterization of Mnk1b, a splice variant of human MAP kinase-interacting kinase Mnk1.". Exp. Cell Res. 299 (2): 343–55. doi:10.1016/j.yexcr.2004.06.006. PMID 15350534.
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): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Worch J, Tickenbrock L, Schwäble J et al. (2005). "The serine-threonine kinase MNK1 is post-translationally stabilized by PML-RARalpha and regulates differentiation of hematopoietic cells.". Oncogene 23 (57): 9162–72. doi:10.1038/sj.onc.1208164. PMID 15516979.
Grund EM, Spyropoulos DD, Watson DK, Muise-Helmericks RC (2005). "Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells.". J. Biol. Chem. 280 (6): 4772–8. doi:10.1074/jbc.M408356200. PMID 15563472.
O'Loghlen A, González VM, Salinas M, Martín ME (2005). "Suppression of human Mnk1 by small interfering RNA increases the eukaryotic initiation factor 4F activity in HEK293T cells.". FEBS Lett. 578 (1-2): 31–5. doi:10.1016/j.febslet.2004.10.063. PMID 15581611.

PDB gallery

2hw6: Crystal structure of Mnk1 catalytic domain

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 CDC2L5 CRKRS 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

Biochemistry overview
Enzymes overview
By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
  - 2.7.10
  - 11-12
- 8
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
  - 22
  - 23
  - 24
- 5
- 6
- 7
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

MKNK1

Interactions

References

Further reading