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Protein

Mitogen-activated protein kinase 13

Gene

Mapk13

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei54ATPPROSITE-ProRule annotation1
Active sitei150Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Stress response, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-376172. DSCAM interactions.
R-MMU-4420097. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1346864. Mapk13.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2111473.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862871 – 366Mitogen-activated protein kinase 13Add BLAST366

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei180Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7By similarity1
Modified residuei182PhosphotyrosineCombined sources1
Modified residuei350PhosphoserineBy similarity1

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

iPTMnetiQ9Z1B7.
PhosphoSitePlusiQ9Z1B7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000004864.
CleanExiMM_MAPK13.
ExpressionAtlasiQ9Z1B7. baseline and differential.
GenevisibleiQ9Z1B7. MM.

Interactioni

Subunit structurei

Interacts with MAPK8IP2.1 Publication

Protein-protein interaction databases

BioGridi204968. 82 interactors.
STRINGi10090.ENSMUSP00000004986.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1B7.
SMRiQ9Z1B7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 308Protein kinasePROSITE-ProRule annotationAdd BLAST284

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi180 – 182TXY3

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ9Z1B7.
KOiK04441.
OMAiEWKQHIY.
OrthoDBiEOG091G08QL.
PhylomeDBiQ9Z1B7.
TreeFamiTF105100.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom_sf.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
PRINTSiPR01773. P38MAPKINASE.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti45K → R in AAD09229 (Ref. 1) Curated1

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.

Similar proteinsi

Entry informationi

Entry nameiMK13_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1B7
Secondary accession number(s): Q99M57
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 12, 2003
Last modified: November 22, 2017
This is version 152 of the entry and version 2 of the sequence. See 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