Tag |
Content |
dbPAF ID |
dbPAF-0000394 |
Uniprot Accession |
O08911; MK12_MOUSE; Q9D0M4; |
Genbank Protein ID |
NP_038899.1; |
Genbank Nucleotide ID |
NM_013871.3; |
Protein Name |
Mitogen-activated protein kinase 12 |
Protein Synonyms/Alias |
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Gene Name |
Mapk12 |
Gene Synonyms/Alias |
Sapk3; |
Organism |
Mus musculus(Mouse) |
NCBI Taxa ID |
10090 |
Functional Description (View all) |
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.Functional 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.
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Phosphorylation Sites
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dbPAF PTMs: 5 |
Sequence (Fasta) | MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG NKVAIKKLYR 60 PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDESLD DFTDFYLVMP FMGTDLGKLM 120 KHETLSEDRI QFLVYQMLKG LKYIHAAGVI HRDLKPGNLA VNEDCELKIL DFGLARQADS 180 EMTGYVVTRW YRAPEVILNW MRYTQTVDIW SVGCIMAEMI TGKILFKGND HLDQLKEIMK 240 ITGTPPPEFV QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLER MLVLDAEQRV 300 TAAEALTHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS FKPPRQLGAR 360 VPKETAL
368Fasta Sequence
>O08911|Mapk12|Mus musculus(Mouse) MSSPPPARKGFYRQEVTKTAWEVRAVYQDLQPVGSGAYGAVCSAVDSRTGNKVAIKKLYRPFQSELFAKRAYRELRLLKHMRHENVIGLLDVFTPDESLDDFTDFYLVMPFMGTDLGKLMKHETLSEDRIQFLVYQMLKGLKYIHAAGVIHRDLKPGNLAVNEDCELKILDFGLARQADSEMTGYVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKILFKGNDHLDQLKEIMKITGTPPPEFVQKLQSAEAKNYMEGLPELEKKDFASVLTNASPQAVNLLERMLVLDAEQRVTAAEALTHPYFESLRDTEDEPKAQKYDDSFDDVDRTLEEWKRVTYKEVLSFKPPRQLGARVPKETAL
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Keyword |
KW-0067--ATP-binding KW-0131--Cell cycle KW-0181--Complete proteome KW-0963--Cytoplasm KW-0418--Kinase KW-0460--Magnesium KW-0479--Metal-binding KW-0496--Mitochondrion KW-0547--Nucleotide-binding KW-0539--Nucleus KW-0597--Phosphoprotein KW-1185--Reference proteome KW-0723--Serine/threonine-protein kinase KW-0346--Stress response KW-0804--Transcription KW-0805--Transcription regulation KW-0808--Transferase KW-0832--Ubl conjugation
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Interpro |
IPR011009--Kinase-like_dom IPR003527--MAP_kinase_CS IPR008352--MAPK_p38 IPR000719--Prot_kinase_dom IPR017441--Protein_kinase_ATP_BS IPR002290--Ser/Thr_dual-sp_kinase
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PROSITE |
PS01351--MAPK PS00107--PROTEIN_KINASE_ATP PS50011--PROTEIN_KINASE_DOM
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Pfam |
PF00069--Pkinase
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Gene Ontology |
GO:0005737--C:cytoplasm GO:0005739--C:mitochondrion GO:0005654--C:nucleoplasm GO:0005524--F:ATP binding GO:0000287--F:magnesium ion binding GO:0004707--F:MAP kinase activity GO:0004674--F:protein serine/threonine kinase activity GO:0007049--P:cell cycle GO:0045445--P:myoblast differentiation GO:0045786--P:negative regulation of cell cycle GO:0018105--P:peptidyl-serine phosphorylation GO:0006355--P:regulation of transcription, DNA-templated GO:0006351--P:transcription, DNA-templated
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