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Protein

Mitogen-activated protein kinase 12

Gene

Mapk12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+Note: Binds 2 magnesium ions.

Enzyme regulationi

Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei56ATPPROSITE-ProRule annotation1
Active sitei153Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi33 – 41ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Stress response, Transcription, Transcription regulation
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-375170 CDO in myogenesis
R-MMU-376172 DSCAM interactions
R-MMU-4420097 VEGFA-VEGFR2 Pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 12 (EC:2.7.11.24)
Short name:
MAP kinase 12
Short name:
MAPK 12
Alternative name(s):
Extracellular signal-regulated kinase 6
Short name:
ERK-6
Mitogen-activated protein kinase p38 gamma
Short name:
MAP kinase p38 gamma
Stress-activated protein kinase 3
Gene namesi
Name:Mapk12
Synonyms:Sapk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1353438 Mapk12

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2111473

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862831 – 367Mitogen-activated protein kinase 12Add BLAST367

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei183PhosphothreonineCombined sources1
Modified residuei185PhosphotyrosineCombined sources1

Post-translational modificationi

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.1 Publication
Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO08911
PaxDbiO08911
PeptideAtlasiO08911
PRIDEiO08911

PTM databases

iPTMnetiO08911
PhosphoSitePlusiO08911

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle. Also expressed in the heart, particularly in cardiac myocytes, lung, thymus and testes.1 Publication

Gene expression databases

BgeeiENSMUSG00000022610
CleanExiMM_MAPK12
GenevisibleiO08911 MM

Interactioni

Subunit structurei

Monomer. Interacts with the PDZ domain of the syntrophin SNTA1 (By similarity). Interacts with SH3BP5, LIN7C, SCRIB and SYNJ2BP (By similarity).By similarity

Protein-protein interaction databases

DIPiDIP-49622N
IntActiO08911, 2 interactors
STRINGi10090.ENSMUSP00000086207

Structurei

3D structure databases

ProteinModelPortaliO08911
SMRiO08911
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 311Protein kinasePROSITE-ProRule annotationAdd BLAST285

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi183 – 185TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00550000074271
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiO08911
KOiK04441
OMAiMSSGAMD
OrthoDBiEOG091G08QL
PhylomeDBiO08911
TreeFamiTF105100

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008352 MAPK_p38
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01773 P38MAPKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequencei

Sequence statusi: Complete.

O08911-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG
60 70 80 90 100
NKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDESLD
110 120 130 140 150
DFTDFYLVMP FMGTDLGKLM KHETLSEDRI QFLVYQMLKG LKYIHAAGVI
160 170 180 190 200
HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW
210 220 230 240 250
MRYTQTVDIW SVGCIMAEMI TGKILFKGND HLDQLKEIMK ITGTPPPEFV
260 270 280 290 300
QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLER MLVLDAEQRV
310 320 330 340 350
TAAEALTHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS
360
FKPPRQLGAR VPKETAL
Length:367
Mass (Da):42,043
Last modified:July 1, 1997 - v1
Checksum:iAB36A40EF3C59981
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13439 mRNA Translation: CAA73850.1
AK011286 mRNA No translation available.
BC021640 mRNA Translation: AAH21640.1
CCDSiCCDS27740.1
RefSeqiNP_038899.1, NM_013871.3
UniGeneiMm.38343

Genome annotation databases

EnsembliENSMUST00000088827; ENSMUSP00000086207; ENSMUSG00000022610
GeneIDi29857
KEGGimmu:29857
UCSCiuc007xfl.2 mouse

Similar proteinsi

Entry informationi

Entry nameiMK12_MOUSE
AccessioniPrimary (citable) accession number: O08911
Secondary accession number(s): Q9D0M4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: March 28, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health