Tchem MKNK2 MAP kinase-interacting serine/threonine-protein kinase 2

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Map Kinase-interacting Serine/threonine-protein Kinase 2

Protein / Cytoskeletal Protein / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Map Kinase-interacting Serine/threonine-protein Kinase 2

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Mapkapk Family / Mnk Subfamily / Map Kinase-interacting Serine/threonine-protein Kinase 2

Protein Summary

Description

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. This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization. [provided by RefSeq, Aug 2011]

Uniprot Accession IDs

• Q9HBH9
• Q6GPI3
• Q9HBH8
• Q9UHR0
• Q9Y2N6

Gene Name

• MKNK2

Ensembl ID

• ENST00000250896
• ENSP00000250896
• ENSG00000099875
• ENST00000309340
• ENSP00000309485
• ENST00000591601
• ENSP00000467811

Symbol

• GPRK7
• MNK2
• MNK2
• GPRK7

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
small molecule	1
molecular function	0.97
transcription factor binding site profile	0.79
kinase perturbation	0.76
microRNA	0.76

Related Tools

Dark Kinase Knowledgebase

The Dark Kinase Knowledgebase is an an online compendium of knowledge and experimental results of understudied kinases.

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ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 32.33   (req: < 5)

Gene RIFs: 13   (req: <= 3)

Antibodies: 283   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 32.33   (req: >= 5)

Gene RIFs: 13   (req: > 3)

Antibodies: 283   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 377

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

IDG Resources

Reagents (1)

Data Resources (1)

Chemical Tool

N-(2-methoxyethyl)-4-((6-(pyridin-4-yl)quinazolin-2-yl)amino)benzamide

Details:

• ChEBI: 143119
• Provider: UNC-CH
• Activity: 156 nM
• Selectivity: 0.037

Data:

• UNC-BE1-004

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https://www.sgc-unc.org/request-idg-tools

Approved Drugs (1)

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1 – 1 of 1

apomorphine

MKNK2Tchem Kinase

IC50 : 7.6

Active Ligands (377)

Explore Active Ligands

1 – 10 of 377

CHEMBL388978

MKNK2Tchem Kinase

Kd : 7.77

CHEMBL603469

MKNK2Tchem Kinase

Kd : 8.85

CHEMBL1230609

MKNK2Tchem Kinase

Kd : 8.43

CHEMBL574738

MKNK2Tchem Kinase

Kd : 8.52

CHEMBL259084

MKNK2Tchem Kinase

IC50 : 7.89

CHEMBL3806189

MKNK2Tchem Kinase

IC50 : 8

CHEMBL3805771

MKNK2Tchem Kinase

IC50 : 7.8

MELK-TI

MKNK2Tchem Kinase

IC50 : 6.11999989

tomivosertib

MKNK2Tchem Kinase

IC50 : 9

CHEMBL1200596

MKNK2Tchem Kinase

IC50 : 7.92

GWAS Traits (1)

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5

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	1	1	1		55.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	1		55.4

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Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	MAP kinase interacting serine/threonine kinase 2	VGNC:13225	455561
Macaque	MAP kinase interacting serine/threonine kinase 2		721436
Mouse	MAP kinase-interacting serine/threonine kinase 2	MGI:894279	17347
Rat	MAP kinase-interacting serine/threonine kinase 2	RGD:1305728	299618
Dog	MAP kinase interacting serine/threonine kinase 2	VGNC:43251	612212

Species	Name	OMA	EggNOG	Inparanoid
Chimp	MAP kinase interacting serine/threonine kinase 2
Macaque	MAP kinase interacting serine/threonine kinase 2
Mouse	MAP kinase-interacting serine/threonine kinase 2
Rat	MAP kinase-interacting serine/threonine kinase 2
Dog	MAP kinase interacting serine/threonine kinase 2

Protein Structure (11 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9HBH9-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 11

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (161)

KEGG (3)

PathwayCommons (4)

WikiPathways (154)

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1 – 3 of 3

Data Source	Name	Explore in Pharos	Explore in Source
KEGG	HIF-1 signaling pathway	109 targets	path:hsa04066
KEGG	MAPK signaling pathway	295 targets	path:hsa04010
KEGG	Insulin signaling pathway	137 targets	path:hsa04910

Name	Explore in Pharos	Explore in Source
HIF-1 signaling pathway	109 targets	path:hsa04066
MAPK signaling pathway	295 targets	path:hsa04010
Insulin signaling pathway	137 targets	path:hsa04910

Gene Ontology Terms (18)

Functions (5)

Components (5)

Processes (8)

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10

1 – 5 of 5

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
calcium-dependent protein serine/threonine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
calmodulin-dependent protein kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (33)

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1 – 10 of 33

• See Interactions on String-DB

MAPK14

Tchem

Family: Kinase

Novelty: 0.00045138

p_int: 0.999535612

p_ni: 1e-9

p_wrong: 0.000464387

Score: 0.683

Data Source: BioPlex,STRINGDB

MAPK1

Tchem

Family: Kinase

Novelty: 0.00061058

Score: 0.964

Data Source: STRINGDB

MAPK3

Tchem

Family: Kinase

Novelty: 0.00012969

Score: 0.942

Data Source: STRINGDB

EIF4E

Tchem

Novelty: 0.00072182

Score: 0.884

Data Source: STRINGDB

EIF4E1B

Tdark

Novelty: 0.28023341

Score: 0.827

Data Source: STRINGDB

EIF4E2

Tbio

Novelty: 0.0490219

Score: 0.822

Data Source: STRINGDB

MKNK1

Tchem

Family: Kinase

Novelty: 0.01445137

Score: 0.809

Data Source: STRINGDB

ATF4

Tbio

Family: TF

Novelty: 0.00253408

Score: 0.808

Data Source: STRINGDB

SRPK1

Tchem

Family: Kinase

Novelty: 0.01066655

Score: 0.678

Data Source: STRINGDB

EIF4G1

Tbio

Novelty: 0.00170995

Score: 0.665

Data Source: STRINGDB

Publication Statistics

PubMed Score  32.33

PubMed score by year

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PubTator Score  37.42

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

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Structural Annotations

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Apoptosis
ATP-binding
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Nucleotide-binding

GWAS Trait Find Similar Targets

mathematical ability