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O08911 (MK12_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 12

Short name=MAP kinase 12
Short name=MAPK 12
EC=2.7.11.24
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 names
Name:Mapk12
Synonyms:Sapk3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length367 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5 Ref.7 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 2 magnesium ions.

Enzyme regulation

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. Ref.6

Subunit structure

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

Subcellular location

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

Tissue specificity

Highly expressed in skeletal muscle. Also expressed in the heart, particularly in cardiac myocytes, lung, thymus and testes. Ref.4

Domain

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

Post-translational modification

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme. Ref.6

Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 367367Mitogen-activated protein kinase 12
PRO_0000186283

Regions

Domain27 – 311285Protein kinase
Nucleotide binding33 – 419ATP By similarity
Motif183 – 1853TXY

Sites

Active site1531Proton acceptor By similarity
Binding site561ATP By similarity

Amino acid modifications

Modified residue1831Phosphothreonine; by MAP2K3 and MAP2K6 By similarity
Modified residue1851Phosphotyrosine; by MAP2K3 and MAP2K6 By similarity

Sequences

Sequence LengthMass (Da)Tools
O08911 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: AB36A40EF3C59981

FASTA36742,043
        10         20         30         40         50         60 
MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG NKVAIKKLYR 

        70         80         90        100        110        120 
PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDESLD DFTDFYLVMP FMGTDLGKLM 

       130        140        150        160        170        180 
KHETLSEDRI QFLVYQMLKG LKYIHAAGVI HRDLKPGNLA VNEDCELKIL DFGLARQADS 

       190        200        210        220        230        240 
EMTGYVVTRW YRAPEVILNW MRYTQTVDIW SVGCIMAEMI TGKILFKGND HLDQLKEIMK 

       250        260        270        280        290        300 
ITGTPPPEFV QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLER MLVLDAEQRV 

       310        320        330        340        350        360 
TAAEALTHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS FKPPRQLGAR 


VPKETAL 

« Hide

References

« Hide 'large scale' references
[1]Goedert M., Craxton M.
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryo.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
[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: TISSUE SPECIFICITY.
[5]"p38-{gamma}-dependent gene silencing restricts entry into the myogenic differentiation program."
Gillespie M.A., Le Grand F., Scime A., Kuang S., von Maltzahn J., Seale V., Cuenda A., Ranish J.A., Rudnicki M.A.
J. Cell Biol. 187:991-1005(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Differential activation of p38MAPK isoforms by MKK6 and MKK3."
Remy G., Risco A.M., Inesta-Vaquera F.A., Gonzalez-Teran B., Sabio G., Davis R.J., Cuenda A.
Cell. Signal. 22:660-667(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, ENZYME REGULATION.
[7]"p38gamma regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage."
Wu C.C., Wu X., Han J., Sun P.
Protein Cell 1:573-583(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Evidence of p38gamma and p38delta involvement in cell transformation processes."
Cerezo-Guisado M.I., del Reino P., Remy G., Kuma Y., Arthur J.S., Gallego-Ortega D., Cuenda A.
Carcinogenesis 32:1093-1099(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y13439 mRNA. Translation: CAA73850.1.
AK011286 mRNA. No translation available.
BC021640 mRNA. Translation: AAH21640.1.
CCDSCCDS27740.1.
RefSeqNP_038899.1. NM_013871.3.
UniGeneMm.38343.

3D structure databases

ProteinModelPortalO08911.
SMRO08911. Positions 8-353.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO08911. 1 interaction.
MINTMINT-1550872.
STRING10090.ENSMUSP00000086207.

Chemistry

BindingDBO08911.
ChEMBLCHEMBL2111473.

PTM databases

PhosphoSiteO08911.

Proteomic databases

MaxQBO08911.
PaxDbO08911.
PRIDEO08911.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000088827; ENSMUSP00000086207; ENSMUSG00000022610.
GeneID29857.
KEGGmmu:29857.
UCSCuc007xfl.2. mouse.

Organism-specific databases

CTD6300.
MGIMGI:1353438. Mapk12.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00680000099969.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidO08911.
KOK04441.
OMANFKPPQT.
OrthoDBEOG7PCJGV.
PhylomeDBO08911.
TreeFamTF105100.

Enzyme and pathway databases

ReactomeREACT_224594. Organelle biogenesis and maintenance.

Gene expression databases

ArrayExpressO08911.
BgeeO08911.
CleanExMM_MAPK12.
GenevestigatorO08911.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01773. P38MAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio307054.
PROO08911.
SOURCESearch...

Entry information

Entry nameMK12_MOUSE
AccessionPrimary (citable) accession number: O08911
Secondary accession number(s): Q9D0M4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot