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Q63538

- MK12_RAT

UniProt

Q63538 - MK12_RAT

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Protein

Mitogen-activated protein kinase 12

Gene
Mapk12, Sapk3
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - 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

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei56 – 561ATP By similarity
Active sitei153 – 1531Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi33 – 419ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: RGD
  2. magnesium ion binding Source: Ensembl
  3. MAP kinase activity Source: RGD
  4. protein binding Source: IntAct
  5. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. MAPK cascade Source: GOC
  3. myoblast differentiation Source: Ensembl
  4. negative regulation of cell cycle Source: UniProtKB
  5. peptidyl-serine phosphorylation Source: Ensembl
  6. protein phosphorylation Source: RGD
  7. regulation of transcription, DNA-templated Source: UniProtKB-KW
  8. response to stress Source: UniProtKB-KW
  9. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_209077. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 7

Organism-specific databases

RGDi70975. Mapk12.

Subcellular locationi

Cytoplasm. Nucleus By similarity. Mitochondrion
Note: Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma.3 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. mitochondrion Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi183 – 1831T → A: Loss of kinase activity. 1 Publication
Mutagenesisi185 – 1851Y → A: Loss of kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 367367Mitogen-activated protein kinase 12PRO_0000186284Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei183 – 1831Phosphothreonine; by MAP2K3 and MAP2K61 Publication
Modified residuei185 – 1851Phosphotyrosine; by MAP2K3 and MAP2K61 Publication

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.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ63538.

PTM databases

PhosphoSiteiQ63538.

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

GenevestigatoriQ63538.

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 a different organism.

Protein-protein interaction databases

BioGridi248795. 1 interaction.
IntActiQ63538. 1 interaction.
STRINGi10116.ENSRNOP00000046455.

Structurei

3D structure databases

ProteinModelPortaliQ63538.
SMRiQ63538. Positions 8-353.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 311285Protein kinaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi183 – 1853TXY

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00680000099969.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ63538.
KOiK04441.
OMAiNFKPPQT.
OrthoDBiEOG7PCJGV.
PhylomeDBiQ63538.
TreeFamiTF105100.

Family and domain databases

InterProiIPR011009. 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_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63538-1 [UniParc]FASTAAdd to Basket

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MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG    50
NKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD 100
DFTDFYLVMP FMGTDLGKLM KHETLSEDRI QFLVYQMLKG LKYIHAAGVI 150
HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW 200
MRYTQTVDIW SVGCIMAEMI TGKILFKGND HLDQLKEIMK VTGTPPPEFV 250
QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLEK MLVLDAEQRV 300
TAAEALAHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS 350
FKPPRQLGAR VPKETAL 367
Length:367
Mass (Da):41,985
Last modified:November 1, 1996 - v1
Checksum:iB77193D9F45E1D4E
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X96488 mRNA. Translation: CAA65342.1 .
PIRi S68680.
RefSeqi NP_068514.1. NM_021746.1.
UniGenei Rn.162968.

3D structure databases

ProteinModelPortali Q63538.
SMRi Q63538. Positions 8-353.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248795. 1 interaction.
IntActi Q63538. 1 interaction.
STRINGi 10116.ENSRNOP00000046455.

PTM databases

PhosphoSitei Q63538.

Proteomic databases

PRIDEi Q63538.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000044376 ; ENSRNOP00000046455 ; ENSRNOG00000031233 .
GeneIDi 60352.
KEGGi rno:60352.

Organism-specific databases

CTDi 6300.
RGDi 70975. Mapk12.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00680000099969.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi Q63538.
KOi K04441.
OMAi NFKPPQT.
OrthoDBi EOG7PCJGV.
PhylomeDBi Q63538.
TreeFami TF105100.

Enzyme and pathway databases

Reactomei REACT_209077. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.

Miscellaneous databases

NextBioi 612019.
PROi Q63538.

Gene expression databases

Genevestigatori Q63538.

Family and domain databases

InterProi 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_dom.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01773. P38MAPKINASE.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases."
    Mertens S., Craxton M., Goedert M.
    FEBS Lett. 383:273-276(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. Cited for: INTERACTION WITH SNTA1, FUNCTION IN PHOSPHORYLATION OF SNTA1, SUBCELLULAR LOCATION.
  3. "Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells."
    Conrad P.W., Rust R.T., Han J., Millhorn D.E., Beitner-Johnson D.
    J. Biol. Chem. 274:23570-23576(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-183 AND TYR-185, MUTAGENESIS OF THR-183 AND TYR-185.
  4. "Cardiac expression and subcellular localization of the p38 mitogen-activated protein kinase member, stress-activated protein kinase-3 (SAPK3)."
    Court N.W., dos Remedios C.G., Cordell J., Bogoyevitch M.A.
    J. Mol. Cell. Cardiol. 34:413-426(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Phosphorylation of the mitochondrial protein Sab by stress-activated protein kinase 3."
    Court N.W., Kuo I., Quigley O., Bogoyevitch M.A.
    Biochem. Biophys. Res. Commun. 319:130-137(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SH3BP5.
  6. "Outer membrane protein 25-a mitochondrial anchor and inhibitor of stress-activated protein kinase-3."
    Court N.W., Ingley E., Klinken S.P., Bogoyevitch M.A.
    Biochim. Biophys. Acta 1744:68-75(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LIN7C; SCRIB AND SYNJ2BP, ENZYME REGULATION.
  7. "Mechanisms and functions of p38 MAPK signalling."
    Cuadrado A., Nebreda A.R.
    Biochem. J. 429:403-417(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.

Entry informationi

Entry nameiMK12_RAT
AccessioniPrimary (citable) accession number: Q63538
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: September 3, 2014
This is version 126 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

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