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Q9Z1B7

- MK13_MOUSE

UniProt

Q9Z1B7 - MK13_MOUSE

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Protein

Mitogen-activated protein kinase 13

Gene

Mapk13

Organism
Mus musculus (Mouse)
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. 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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei54 – 541ATPPROSITE-ProRule annotation
Active sitei150 – 1501Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. intracellular signal transduction Source: UniProtKB
  3. MAPK cascade Source: GOC
  4. peptidyl-serine phosphorylation Source: Ensembl
  5. positive regulation of interleukin-6 production Source: Ensembl
  6. regulation of transcription, DNA-templated Source: UniProtKB-KW
  7. response to osmotic stress Source: Ensembl
  8. 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, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_207601. p38MAPK events.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_243212. DSCAM interactions.
REACT_257088. VEGFA-VEGFR2 Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 13 (EC:2.7.11.24)
Short name:
MAP kinase 13
Short name:
MAPK 13
Alternative name(s):
Mitogen-activated protein kinase p38 delta
Short name:
MAP kinase p38 delta
Stress-activated protein kinase 4
Gene namesi
Name:Mapk13
Synonyms:Serk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:1346864. Mapk13.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 366366Mitogen-activated protein kinase 13PRO_0000186287Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7By similarity
Modified residuei182 – 1821Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7By similarity
Modified residuei350 – 3501PhosphoserineBy similarity

Post-translational modificationi

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).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Z1B7.
PaxDbiQ9Z1B7.
PRIDEiQ9Z1B7.

PTM databases

PhosphoSiteiQ9Z1B7.

Expressioni

Gene expression databases

BgeeiQ9Z1B7.
CleanExiMM_MAPK13.
ExpressionAtlasiQ9Z1B7. baseline and differential.
GenevestigatoriQ9Z1B7.

Interactioni

Subunit structurei

Interacts with MAPK8IP2.1 Publication

Protein-protein interaction databases

BioGridi204968. 82 interactions.
STRINGi10090.ENSMUSP00000004986.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1B7.
SMRiQ9Z1B7. Positions 2-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 308284Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi180 – 1823TXY

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ9Z1B7.
KOiK04441.
OMAiEHPYFDN.
OrthoDBiEOG7PCJGV.
PhylomeDBiQ9Z1B7.
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.
[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.

Q9Z1B7-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSLTRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK
60 70 80 90 100
VAIKKLSRPF QSEIFAKRAY RELLLLKHMH HENVIGLLDV FTPASSLRSF
110 120 130 140 150
HDFYLVMPFM QTDLQKIMGM EFSEDKVQYL VYQMLKGLKY IHSAGIVHRD
160 170 180 190 200
LKPGNLAVNE DCELKILDFG LARHTDTEMT GYVVTRWYRA PEVILSWMHY
210 220 230 240 250
NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG VPGAEFVQKL
260 270 280 290 300
KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AADLLDKMLE LDVDKRLTAA
310 320 330 340 350
QALAHPFFEP FRDPEEETEA QQPFDDALEH EKLSVDEWKQ HIYKEISNFS
360
PIARKDSRRR SGMKLQ
Length:366
Mass (Da):42,072
Last modified:February 12, 2003 - v2
Checksum:i45D23D7BD404B3FE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti45 – 451K → R in AAD09229. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81823 mRNA. Translation: AAD09229.1.
BC001992 mRNA. Translation: AAH01992.1.
CCDSiCCDS28584.1.
RefSeqiNP_036080.2. NM_011950.2.
UniGeneiMm.27970.

Genome annotation databases

EnsembliENSMUST00000004986; ENSMUSP00000004986; ENSMUSG00000004864.
GeneIDi26415.
KEGGimmu:26415.
UCSCiuc008bro.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81823 mRNA. Translation: AAD09229.1 .
BC001992 mRNA. Translation: AAH01992.1 .
CCDSi CCDS28584.1.
RefSeqi NP_036080.2. NM_011950.2.
UniGenei Mm.27970.

3D structure databases

ProteinModelPortali Q9Z1B7.
SMRi Q9Z1B7. Positions 2-351.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204968. 82 interactions.
STRINGi 10090.ENSMUSP00000004986.

Chemistry

ChEMBLi CHEMBL2111473.

PTM databases

PhosphoSitei Q9Z1B7.

Proteomic databases

MaxQBi Q9Z1B7.
PaxDbi Q9Z1B7.
PRIDEi Q9Z1B7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000004986 ; ENSMUSP00000004986 ; ENSMUSG00000004864 .
GeneIDi 26415.
KEGGi mmu:26415.
UCSCi uc008bro.2. mouse.

Organism-specific databases

CTDi 5603.
MGIi MGI:1346864. Mapk13.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074271.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi Q9Z1B7.
KOi K04441.
OMAi EHPYFDN.
OrthoDBi EOG7PCJGV.
PhylomeDBi Q9Z1B7.
TreeFami TF105100.

Enzyme and pathway databases

Reactomei REACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_207601. p38MAPK events.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_243212. DSCAM interactions.
REACT_257088. VEGFA-VEGFR2 Pathway.

Miscellaneous databases

ChiTaRSi Mapk13. mouse.
NextBioi 304421.
PROi Q9Z1B7.
SOURCEi Search...

Gene expression databases

Bgeei Q9Z1B7.
CleanExi MM_MAPK13.
ExpressionAtlasi Q9Z1B7. baseline and differential.
Genevestigatori Q9Z1B7.

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.
[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

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiMK13_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1B7
Secondary accession number(s): Q99M57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 12, 2003
Last modified: November 26, 2014
This is version 130 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3