InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPK12

Summary

InnateDB Protein

IDBP-13095.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAPK12

Protein Name

mitogen-activated protein kinase 12

Synonyms

ERK3; ERK6; P38GAMMA; PRKM12; SAPK-3; SAPK3;

Species

Homo sapiens

Ensembl Protein

ENSP00000215659

InnateDB Gene

IDBG-13093 (MAPK12)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:10848581, ECO:0000269PubMed:14592936, ECO:0000269PubMed:17724032, ECO:0000269PubMed:20605917, ECO:0000269PubMed:21172807, ECO:0000269PubMed:8633070, ECO:0000269PubMed:9430721}.

Subcellular Localization

Cytoplasm. Nucleus. Mitochondrion. Note=Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma (By similarity). {ECO:0000250}.

Disease Associations

Note=MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.

Tissue Specificity

Highly expressed in skeletal muscle and heart. {ECO:0000269PubMed:11991731, ECO:0000269PubMed:8633070}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	26 [view]
Protein-Protein	24 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004707	MAP kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006975	DNA damage induced protein phosphorylation
GO:0007050	cell cycle arrest
GO:0007165	signal transduction
GO:0007265	Ras protein signal transduction
GO:0007517	muscle organ development
GO:0018105	peptidyl-serine phosphorylation
GO:0042692	muscle cell differentiation
GO:0045445	myoblast differentiation
GO:0045786	negative regulation of cell cycle
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051149	positive regulation of muscle cell differentiation

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR008352 Mitogen-activated protein (MAP) kinase, p38
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109
PR01773

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt