MAP kinase-interacting serine/threonine-protein kinase 2

UniProt Q9HBH9 Organism Homo sapiens Gene GPRK7, MKNK2, MNK2 EC 2.7.11.1

Also known as: GPRK7, MKNK2, MNK2

Function

Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: CDPK_Ser/Thr_kinases, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 15

2AC3 X-ray 2.10A
2AC5 X-ray 3.20A
2HW7 X-ray 2.71A
6CJ5 X-ray 2.80A
6CJE X-ray 3.36A
6CJH X-ray 3.60A
6CJW X-ray 3.38A
6CJY X-ray 3.05A
6CK3 X-ray 2.90A
6CK6 X-ray 3.32A
6CKI X-ray 2.95A
6JLR X-ray 2.90A
… and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

Drugs targeting this protein · 1

TOMIVOSERTIB inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

MAP kinase-interacting serine/threonine-protein kinase 2 3 shared papers
MAP kinase-interacting serine/threonine-protein kinase 1 1 shared papers
Heterogeneous nuclear ribonucleoprotein A1 1 shared papers
Splicing factor, proline- and glutamine-rich 1 shared papers
Eukaryotic translation initiation factor 4E 2 shared papers
Mitogen-activated protein kinase 11 1 shared papers
Eukaryotic translation initiation factor 4 gamma 1 1 shared papers
Mitogen-activated protein kinase 14 1 shared papers
Mitogen-activated protein kinase 1 1 shared papers

Literature · 22 cited papers

Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis. J. Biol. Chem. · 2011
Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E. Neoplasia · 2010
Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G interaction. Mol. Cell. Biol. · 2010
Discovery of mitogen-activated protein kinase-interacting kinase 1 inhibitors by a comprehensive fragment-oriented virtual screening approach. J. Med. Chem. · 2010
Negative regulatory effects of Mnk kinases in the generation of chemotherapy-induced antileukemic responses. Mol. Pharmacol. · 2010
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front. Biosci. · 2008
Regulation of arsenic trioxide-induced cellular responses by Mnk1 and Mnk2. J. Biol. Chem. · 2008
The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. J. Biol. Chem. · 2008
… and 10 more in the literature graph

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