Tchem MAPK12 Mitogen-activated protein kinase 12

Protein Summary

Description

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P53778
• Q14260
• Q6IC53
• Q99588
• Q99672
• MAP kinase 12

Gene Name

• MAPK12

Ensembl ID

• ENST00000215659
• ENSP00000215659
• ENSG00000188130
• ENST00000622558
• ENSP00000479972

Symbol

• ERK6
• SAPK3
• ERK3
• ERK6
• ERK-6
• SAPK3
• PRKM12
• SAPK-3
• MAPK 12
• P38GAMMA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
kinase perturbation	0.88
protein domain	0.85
biological process	0.84
PubMedID	0.76

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Mitogen-activated Protein Kinase 12

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Mapk Family / P38 Subfamily / Mitogen-activated Protein Kinase 12

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: 116.3   (req: < 5)

Gene RIFs: 37   (req: <= 3)

Antibodies: 496   (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: 116.3   (req: >= 5)

Gene RIFs: 37   (req: > 3)

Antibodies: 496   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

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

Active Ligands: 7

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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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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Approved Drugs (0)

No approved drugs found

Active Ligands (7)

Explore Active Ligands

1 – 7 of 7

AST-487

MAPK12Tchem Kinase

pKd : 7.77

doramapimod

MAPK12Tchem Kinase

pKd : 7.7

US8933228, 3

MAPK12Tchem Kinase

pIC50 : 9

US8933228, 13

MAPK12Tchem Kinase

pIC50 : 8.4

US8933228, 18

MAPK12Tchem Kinase

pIC50 : 8.3

US8933228, 29

MAPK12Tchem Kinase

pIC50 : 8.4

US8933228, 26

MAPK12Tchem Kinase

pIC50 : 8.52

Protein-Protein Interactions (232)

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1 – 10 of 232

• See Interactions on String-DB

MAPK13

Tchem

Family:  Kinase

Novelty:  0.01071621

p_int:  0.999989179

p_ni:  1e-9

p_wrong:  0.00001082

Score:  0.948

Data Source:  BioPlex,STRINGDB

MYLK3

Tchem

Family:  Kinase

Novelty:  0.00661904

p_int:  0.998311096

p_ni:  0.001661757

p_wrong:  0.000027147

Score:  0.538

Data Source:  BioPlex,STRINGDB

SLC9A3R2

Tbio

Family:  Transporter

Novelty:  0.01401705

p_int:  0.996637874

p_ni:  0.003356758

p_wrong:  0.000005368

Data Source:  BioPlex

PARP11

Tbio

Family:  Enzyme

Novelty:  0.11901686

p_int:  0.996635725

p_ni:  0.003364097

p_wrong:  1.78e-7

Score:  0.622

Data Source:  BioPlex,STRINGDB

SPANXN4

Tdark

Novelty:  1.91062423

p_int:  0.910520551

p_ni:  0.08759826

p_wrong:  0.00188119

Data Source:  BioPlex

MAP2K6

Tchem

Family:  Kinase

Novelty:  0.00569655

Score:  0.977

Data Source:  STRINGDB

MAP2K3

Tchem

Family:  Kinase

Novelty:  0.00349605

Score:  0.975

Data Source:  STRINGDB

SNTA1

Tbio

Novelty:  0.01668288

Score:  0.972

Data Source:  STRINGDB

MAPKAPK3

Tchem

Family:  Kinase

Novelty:  0.02469147

Score:  0.969

Data Source:  STRINGDB

MAPKAPK2

Tchem

Family:  Kinase

Novelty:  0.00486452

Score:  0.968

Data Source:  STRINGDB

Nearest Tclin Targets (10)

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Upstream (3)

Downstream (7)

1 – 3 of 3

BRAF

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  8

1: Endocrine resistance

2: Neurotrophin signaling pathway

3: FoxO signaling pathway

4: Rap1 signaling pathway

more:  4 more common pathways

RAF1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  23

1: Endocrine resistance

2: Relaxin signaling pathway

3: T cell receptor signaling pathway

4: Fc epsilon RI signaling pathway

more:  19 more common pathways

PGR

Tclin

Family:  Nuclear Receptor

KEGG Distance:  1

Common Pathways:  2

1: Oocyte meiosis

2: Progesterone-mediated oocyte maturation

Pathways (123)

Reactome (21)

KEGG (51)

PathwayCommons (29)

WikiPathways (22)

Activation of PPARGC1A (PGC-1alpha) by phosphorylation (R-HSA-2151209)

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Items per page:

5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of PPARGC1A (PGC-1alpha) by phosphorylation	10 targets	R-HSA-2151209
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	DSCAM interactions	11 targets	R-HSA-376172
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Immune System	2246 targets	R-HSA-168256

Name	Explore in Pharos	Explore in Source
Activation of PPARGC1A (PGC-1alpha) by phosphorylation	10 targets	R-HSA-2151209
Axon guidance	533 targets	R-HSA-422475
DSCAM interactions	11 targets	R-HSA-376172
Developmental Biology	1055 targets	R-HSA-1266738
Immune System	2246 targets	R-HSA-168256

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (20)

Functions (4)

Components (5)

Processes (11)

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1 – 4 of 4

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

Disease Associations ()

No disease associations found

GWAS Traits (21)

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5

1 – 5 of 21

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet count	EFO_0004309	2	3	4		97.7
platelet crit	EFO_0007985	2	3	4		97.7
mitochondrial DNA measurement	EFO_0006312	1	2	2		76.1
eosinophil count	EFO_0004842	2	1	2		68.3
plasminogen activator inhibitor 1 measurement	EFO_0004792	1	1	0	421.8	61.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 21

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet count	EFO_0004309	4		97.7
platelet crit	EFO_0007985	4		97.7
mitochondrial DNA measurement	EFO_0006312	2		76.1
eosinophil count	EFO_0004842	2		68.3
plasminogen activator inhibitor 1 measurement	EFO_0004792	0	421.8	61.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell cycle
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Mitochondrion

GWAS Trait Find Similar Targets

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bipolar disorder
body height
cutaneous melanoma
eosinophil count
eosinophil percentage of leukocytes
hair color
intelligence
liver fibrosis measurement
lymphocyte count
mathematical ability

MGI Phenotype Find Similar Targets

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cardiovascular system phenotype
cellular phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 12	VGNC:12897	747077
Macaque	mitogen-activated protein kinase 12		715745
Mouse	mitogen-activated protein kinase 12	MGI:1353438	29857
Rat	mitogen-activated protein kinase 12	RGD:70975	60352
Dog	mitogen-activated protein kinase 12	VGNC:42993	607023

Species	Name	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 12
Macaque	mitogen-activated protein kinase 12
Mouse	mitogen-activated protein kinase 12
Rat	mitogen-activated protein kinase 12
Dog	mitogen-activated protein kinase 12

Publication Statistics

PubMed Score 116.30

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PubTator Score 59.54

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Related Publications

Text Mined References (73)

GeneRif Annotations (37)

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PMID	Year	Title