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Q9Z1B7 (MK13_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. 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 13

Short name=MAP kinase 13
Short name=MAPK 13
EC=2.7.11.24
Alternative name(s):
Mitogen-activated protein kinase p38 delta
Short name=MAP kinase p38 delta
Stress-activated protein kinase 4
Gene names
Name:Mapk13
Synonyms:Serk4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length366 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. MAPK13 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. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. Ref.4 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.

Subunit structure

Interacts with MAPK8IP2. Ref.3

Domain

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

Post-translational modification

Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1 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 – 366366Mitogen-activated protein kinase 13
PRO_0000186287

Regions

Domain25 – 308284Protein kinase
Nucleotide binding31 – 399ATP By similarity
Motif180 – 1823TXY

Sites

Active site1501Proton acceptor By similarity
Binding site541ATP By similarity

Amino acid modifications

Modified residue1801Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7 By similarity
Modified residue1821Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7 By similarity
Modified residue3501Phosphoserine By similarity

Experimental info

Sequence conflict451K → R in AAD09229. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Z1B7 [UniParc].

Last modified February 12, 2003. Version 2.
Checksum: 45D23D7BD404B3FE

FASTA36642,072
        10         20         30         40         50         60 
MSLTRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK VAIKKLSRPF 

        70         80         90        100        110        120 
QSEIFAKRAY RELLLLKHMH HENVIGLLDV FTPASSLRSF HDFYLVMPFM QTDLQKIMGM 

       130        140        150        160        170        180 
EFSEDKVQYL VYQMLKGLKY IHSAGIVHRD LKPGNLAVNE DCELKILDFG LARHTDTEMT 

       190        200        210        220        230        240 
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG 

       250        260        270        280        290        300 
VPGAEFVQKL KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AADLLDKMLE LDVDKRLTAA 

       310        320        330        340        350        360 
QALAHPFFEP FRDPEEETEA QQPFDDALEH EKLSVDEWKQ HIYKEISNFS PIARKDSRRR 


SGMKLQ 

« Hide

References

« Hide 'large scale' references
[1]Jiang Y., Han J.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
Tissue: Mammary gland.
[3]"Fibroblast growth factor homologous factors are intracellular signaling proteins."
Schoorlemmer J., Goldfarb M.
Curr. Biol. 11:793-797(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK8IP2.
[4]"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: FUNCTION IN PHOSPHORYLATION OF PRKD1.
[5]"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.
[6]"p38delta mitogen-activated protein kinase regulates skin homeostasis and tumorigenesis."
Efimova T.
Cell Cycle 9:498-505(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[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
U81823 mRNA. Translation: AAD09229.1.
BC001992 mRNA. Translation: AAH01992.1.
CCDSCCDS28584.1.
RefSeqNP_036080.2. NM_011950.2.
UniGeneMm.27970.

3D structure databases

ProteinModelPortalQ9Z1B7.
SMRQ9Z1B7. Positions 2-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204968. 82 interactions.
STRING10090.ENSMUSP00000004986.

Chemistry

BindingDBQ9Z1B7.
ChEMBLCHEMBL2111473.

PTM databases

PhosphoSiteQ9Z1B7.

Proteomic databases

MaxQBQ9Z1B7.
PaxDbQ9Z1B7.
PRIDEQ9Z1B7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000004986; ENSMUSP00000004986; ENSMUSG00000004864.
GeneID26415.
KEGGmmu:26415.
UCSCuc008bro.2. mouse.

Organism-specific databases

CTD5603.
MGIMGI:1346864. Mapk13.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00680000099969.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ9Z1B7.
KOK04441.
OMAEHPYFDN.
OrthoDBEOG7PCJGV.
PhylomeDBQ9Z1B7.
TreeFamTF105100.

Enzyme and pathway databases

ReactomeREACT_224594. Organelle biogenesis and maintenance.

Gene expression databases

ArrayExpressQ9Z1B7.
BgeeQ9Z1B7.
CleanExMM_MAPK13.
GenevestigatorQ9Z1B7.

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

NextBio304421.
PROQ9Z1B7.
SOURCESearch...

Entry information

Entry nameMK13_MOUSE
AccessionPrimary (citable) accession number: Q9Z1B7
Secondary accession number(s): Q99M57
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 12, 2003
Last modified: July 9, 2014
This is version 126 of the entry and version 2 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