MAPK12 (mitogen-activated protein kinase 12)

Gene

• Entrez ID: 6300
• Gene name: Mitogen-activated protein kinase 12
• Gene symbol: MAPK12
• Synonyms: ERK-6, ERK3, ERK6, MAPK 12, P38GAMMA, PRKM12, SAPK-3, SAPK3
• Chromosome: 22
• Chromosome location: 22q13.33
• Summary: 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]

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IEA
GO:0000287	Function	Magnesium ion binding	IDA	10508788
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	8633070, 15850461
GO:0004674	Function	Protein serine/threonine kinase activity	TAS	18221368
GO:0004707	Function	MAP kinase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	12761180, 15158451, 19294699, 24550280, 25158884, 25241761, 25416956, 30126976, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006975	Process	DNA damage induced protein phosphorylation	TAS	10848581
GO:0007050	Process	Cell cycle arrest	TAS	10848581
GO:0007165	Process	Signal transduction	TAS	8633070
GO:0007517	Process	Muscle organ development	TAS	8633070
GO:0010952	Process	Positive regulation of peptidase activity	NAS	18221368
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	15850461
GO:0018105	Process	Peptidyl-serine phosphorylation	TAS	18221368
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0045445	Process	Myoblast differentiation	IDA	8633070
GO:0051149	Process	Positive regulation of muscle cell differentiation	TAS

Other IDs

• MIM: 602399
• HGNC: 6874
• e!Ensembl: ENSG00000188130

Protein

• UniProt ID: P53778
• Protein name: Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
• Protein 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.
• PDB: 1CM8, 4QUM, 6UNA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	27 → 311	Protein kinase domain	Domain

• Sequence:

  MSSPPPARSGFYRQEVTKTAWEVRAVYRDLQPVGSGAYGAVCSAVDGRTGAKVAIKKLYR
  PFQSELFAKRAYRELRLLKHMRHENVIGLLDVFTPDETLDDFTDFYLVMPFMGTDLGKLM
  KHEKLGEDRIQFLVYQMLKGLRYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQADS
  EMTGYVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKTLFKGSDHLDQLKEIMK
  VTGTPPAEFVQRLQSDEAKNYMKGLPELEKKDFASILTNASPLAVNLLEKMLVLDAEQRV
  TAGEALAHPYFESLHDTEDEPQVQKYDDSFDDVDRTLDEWKRVTYKEVLSFKPPRQLGAR
  VSKETPL

• Sequence length: 367