Mitogen-activated protein kinase 12 - Rattus norvegicus (Rat)

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Q63538 (MK12_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 116. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	367 AA.
Sequence status	Complete.
Protein existence	Evidence 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.2 Ref.3
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. Interacts with LIN7C, SCRIB, SYNJ2BP and SH3BP5. Ref.2 Ref.5 Ref.6
Subcellular location	Cytoplasm. Nucleus By similarity. Mitochondrion. Note: Mitochondrial when associated with SH3BP5. In skeletal muscle co-localizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma. Ref.2 Ref.4 Ref.5
Tissue specificity	Highly expressed in skeletal muscle, lung and testes and also in the heart and thymus of both adult and neonatal rats. 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.3 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.

Ontologies

Keywords
Biological process	Cell cycle Stress response Transcription Transcription regulation
Cellular component	Cytoplasm Mitochondrion Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW myoblast differentiation Inferred from electronic annotation. Source: Compara negative regulation of cell cycle Inferred from direct assay Ref.3. Source: UniProtKB peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to stress Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.4. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay PubMed 16879317. Source: RGD MAP kinase activity Inferred from direct assay PubMed 16879317. Source: RGD magnesium ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SNTA1	Q13424	5	EBI-783937,EBI-717191	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 367

367

Mitogen-activated protein kinase 12

PRO_0000186284

Regions

Domain

27 – 311

285

Protein kinase

Nucleotide binding

33 – 41

ATP By similarity

Motif

183 – 185

TXY

Sites

Active site

153

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

183

Phosphothreonine; by MAP2K3 and MAP2K6 Ref.3

Modified residue

185

Phosphotyrosine; by MAP2K3 and MAP2K6 Ref.3

Experimental info

Mutagenesis

183

T → A: Loss of kinase activity. Ref.3

Mutagenesis

185

Y → A: Loss of kinase activity. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q63538 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: B77193D9F45E1D4E
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FASTA

367

41,985

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

        70         80         90        100        110        120 
PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD 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 
VTGTPPPEFV QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLEK MLVLDAEQRV 

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


VPKETAL

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References

[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]	"Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis." Sumara G., Formentini I., Collins S., Sumara I., Windak R., Bodenmiller B., Ramracheya R., Caille D., Jiang H., Platt K.A., Meda P., Aebersold R., Rorsman P., Ricci R. Cell 136:235-248(2009) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X96488 mRNA. Translation: CAA65342.1.
IPI	IPI00210037.
PIR	S68680.
RefSeq	NP_068514.1. NM_021746.1.
UniGene	Rn.162968.
3D structure databases
ProteinModelPortal	Q63538.
SMR	Q63538. Positions 8-353.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q63538. 1 interaction.
STRING	10116.ENSRNOP00000046455.
PTM databases
PhosphoSite	Q63538.
Proteomic databases
PRIDE	Q63538.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000044376; ENSRNOP00000046455; ENSRNOG00000031233.
GeneID	60352.
KEGG	rno:60352.
Organism-specific databases
CTD	6300.
RGD	70975. Mapk12.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099969.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	Q63538.
KO	K04441.
OMA	HEKLGED.
Gene expression databases
ArrayExpress	Q63538.
Genevestigator	Q63538.
GermOnline	ENSRNOG00000031233. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR008352. MAPK_p38. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01773. P38MAPKINASE.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	612019.

Entry information

Entry name

MK12_RAT

Accession

Primary (citable) accession number: Q63538

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents