Tchem MAP2K3 Dual specificity mitogen-activated protein kinase kinase 3

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste7 Family / Dual Specificity Mitogen-activated Protein Kinase Kinase 3

Protein Summary

Description

Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P46734
• B3KSK7
• Q99441
• Q9UE71
• Q9UE72
• MAP kinase kinase 3

Gene Name

• MAP2K3

Ensembl ID

• ENST00000316920
• ENSP00000319139
• ENSG00000034152
• ENST00000342679
• ENSP00000345083
• ENST00000361818
• ENSP00000355081
• ENST00000613338
• ENSP00000478619

Symbol

• MEK3
• MKK3
• PRKMK3
• SKK2
• MEK3
• MKK3
• MAPKK3
• PRKMK3
• SAPKK2
• SAPKK-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
interacting protein	0.99
molecular function	0.99
biological process	0.92
pathway	0.91

Related Tools

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: 242.31   (req: < 5)

Gene RIFs: 36   (req: <= 3)

Antibodies: 1253   (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: 242.31   (req: >= 5)

Gene RIFs: 36   (req: > 3)

Antibodies: 1253   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

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

Active Ligands: 5

Tclin

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

Active Drug: 0

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

CHEMBL388978

MAP2K3Tchem Kinase

Kd : 8.3

CHEMBL603469

MAP2K3Tchem Kinase

Kd : 8.3

CHEMBL37493

MAP2K3Tchem Kinase

IC50 : 6

CHEMBL3747095

MAP2K3Tchem Kinase

IC50 : 8.4

CHEMBL3746157

MAP2K3Tchem Kinase

IC50 : 8.4

GWAS Traits (4)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	6	3	6		98.2
waist-hip ratio	EFO_0004343	2	1	2		50.4
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		24.3
body height	EFO_0004339	1	1	1		6.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	6		98.2
waist-hip ratio	EFO_0004343	2		50.4
mean corpuscular hemoglobin concentration	EFO_0004528	1		24.3
body height	EFO_0004339	1		6.2

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Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase kinase 3		705195
Mouse	mitogen-activated protein kinase kinase 3	MGI:1346868	26397
Rat	mitogen activated protein kinase kinase 3	RGD:1306620	303200
Dog	mitogen-activated protein kinase kinase 3	VGNC:42961	489547
Cow	mitogen-activated protein kinase kinase 3	VGNC:31184	516039

Species	Name	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase kinase 3
Mouse	mitogen-activated protein kinase kinase 3
Rat	mitogen activated protein kinase kinase 3
Dog	mitogen-activated protein kinase kinase 3
Cow	mitogen-activated protein kinase kinase 3

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-P46734-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (131)

Reactome (31)

KEGG (16)

PathwayCommons (38)

WikiPathways (46)

Cellular Senescence (R-HSA-2559583)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cellular Senescence	164 targets	R-HSA-2559583
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Cellular responses to stress	392 targets	R-HSA-2262752
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Disease	1105 targets	R-HSA-1643685

Name	Explore in Pharos	Explore in Source
Cellular Senescence	164 targets	R-HSA-2559583
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Cellular responses to stress	392 targets	R-HSA-2262752
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Disease	1105 targets	R-HSA-1643685

Gene Ontology Terms (22)

Functions (5)

Components (4)

Processes (13)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
MAP kinase kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein serine/threonine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein tyrosine kinase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (131)

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1 – 10 of 131

• See Interactions on String-DB

MAP2K6

Tchem

Family: Kinase

Novelty: 0.00569655

p_int: 1

Score: 0.97

Data Source: BioPlex,STRINGDB

MAPK14

Tchem

Family: Kinase

Novelty: 0.00045138

p_int: 0.99999906

p_ni: 9.4e-7

Score: 0.989

Data Source: BioPlex,Reactome,STRINGDB

CD70

Tbio

Novelty: 0.00420393

p_int: 0.999385125

p_ni: 0.000614874

p_wrong: 1e-9

Data Source: BioPlex

LY86

Tbio

Novelty: 0.00314575

p_int: 0.977249158

p_ni: 0.002083312

p_wrong: 0.020667529

Data Source: BioPlex

MAPK11

Tchem

Family: Kinase

Novelty: 0.00545217

Score: 0.983

Data Source: Reactome,STRINGDB

TAOK2

Tchem

Family: Kinase

Novelty: 0.0232708

Score: 0.977

Data Source: STRINGDB

MAPK12

Tchem

Family: Kinase

Novelty: 0.00835017

Score: 0.975

Data Source: STRINGDB

TAB1

Tchem

Family: Kinase

Novelty: 0.00721424

Score: 0.965

Data Source: STRINGDB

MAPK13

Tchem

Family: Kinase

Novelty: 0.01071621

Score: 0.965

Data Source: STRINGDB

MAP3K5

Tchem

Family: Kinase

Novelty: 0.00144614

Score: 0.956

Data Source: Reactome,STRINGDB

Publication Statistics

PubMed Score  242.31

PubMed score by year

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PubTator Score  133.42

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

Acetylation
Alternative splicing
ATP-binding
Complete proteome
Disease mutation
Kinase
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

body height
body mass index
mean corpuscular hemoglobin concentration
waist-hip ratio

MGI Phenotype Find Similar Targets

cardiovascular system phenotype
cellular phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
muscle phenotype