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Protein

Mitogen-activated protein kinase 12

Gene

Mapk12

Organism
Rattus norvegicus (Rat)
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.2 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

  • ATP binding Source: RGD
  • magnesium ion binding Source: Ensembl
  • MAP kinase activity Source: RGD
  • protein serine/threonine kinase activity Source: UniProtKB

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-RNO-168638 NOD1/2 Signaling Pathway
R-RNO-375170 CDO in myogenesis
R-RNO-376172 DSCAM interactions
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi70975 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi183T → A: Loss of kinase activity. 1 Publication1
Mutagenesisi185Y → A: Loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862841 – 367Mitogen-activated protein kinase 12Add BLAST367

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei183Phosphothreonine; by MAP2K3 and MAP2K61 Publication1
Modified residuei185Phosphotyrosine; by MAP2K3 and MAP2K61 Publication1

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

PaxDbiQ63538
PRIDEiQ63538

PTM databases

iPTMnetiQ63538
PhosphoSitePlusiQ63538

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle, lung and testes and also in the heart and thymus of both adult and neonatal rats.1 Publication

Gene expression databases

BgeeiENSRNOG00000031233

Interactioni

Subunit structurei

Monomer. Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with LIN7C, SCRIB, SYNJ2BP and SH3BP5.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SNTA1Q134245EBI-783937,EBI-717191From Homo sapiens.

Protein-protein interaction databases

BioGridi248795, 1 interactor
DIPiDIP-37835N
IntActiQ63538, 3 interactors
STRINGi10116.ENSRNOP00000046455

Structurei

3D structure databases

ProteinModelPortaliQ63538
SMRiQ63538
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
InParanoidiQ63538
KOiK04441
OMAiMSSGAMD
OrthoDBiEOG091G08QL
PhylomeDBiQ63538
TreeFamiTF105100

Family and domain databases

CDDicd07880 STKc_p38gamma, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008352 MAPK_p38-like
IPR038786 p38gamma
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.

Q63538-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG
60 70 80 90 100
NKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD
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 VTGTPPPEFV
260 270 280 290 300
QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLEK MLVLDAEQRV
310 320 330 340 350
TAAEALAHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS
360
FKPPRQLGAR VPKETAL
Length:367
Mass (Da):41,985
Last modified:November 1, 1996 - v1
Checksum:iB77193D9F45E1D4E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X96488 mRNA Translation: CAA65342.1
PIRiS68680
RefSeqiNP_068514.1, NM_021746.1
UniGeneiRn.162968

Genome annotation databases

EnsembliENSRNOT00000044376; ENSRNOP00000046455; ENSRNOG00000031233
GeneIDi60352
KEGGirno:60352

Similar proteinsi

Entry informationi

Entry nameiMK12_RAT
AccessioniPrimary (citable) accession number: Q63538
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 154 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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