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Protein

Mitogen-activated protein kinase 9

Gene

Mapk9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei55ATPPROSITE-ProRule annotation1
Active sitei151Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi33 – 38ATPPROSITE-ProRule annotation6

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • JUN kinase activity Source: UniProtKB
  • protein kinase activity Source: MGI
  • transcription factor binding Source: MGI

GO - Biological processi

  • cellular response to cadmium ion Source: MGI
  • cellular response to organic substance Source: GO_Central
  • cellular response to reactive oxygen species Source: MGI
  • JNK cascade Source: UniProtKB
  • neuron development Source: GO_Central
  • peptidyl-serine phosphorylation Source: MGI
  • positive regulation of apoptotic signaling pathway Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of macrophage derived foam cell differentiation Source: MGI
  • positive regulation of podosome assembly Source: MGI
  • protein localization to tricellular tight junction Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of gene expression Source: GO_Central
  • response to cadmium ion Source: MGI
  • response to mechanical stimulus Source: GO_Central
  • rhythmic process Source: UniProtKB-KW

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 3474.
ReactomeiR-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-MMU-450341. Activation of the AP-1 family of transcription factors.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 9 (EC:2.7.11.24)
Short name:
MAP kinase 9
Short name:
MAPK 9
Alternative name(s):
Stress-activated protein kinase JNK2
c-Jun N-terminal kinase 2
Gene namesi
Name:Mapk9
Synonyms:Jnk2, Prkm9
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1346862. Mapk9.

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2034797.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862741 – 423Mitogen-activated protein kinase 9Add BLAST423

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei183Phosphothreonine; by MAP2K7Combined sources1
Modified residuei185Phosphotyrosine; by MAP2K4Combined sources1

Post-translational modificationi

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9WTU6.
PeptideAtlasiQ9WTU6.
PRIDEiQ9WTU6.

PTM databases

iPTMnetiQ9WTU6.
PhosphoSitePlusiQ9WTU6.

Expressioni

Tissue specificityi

All four isoforms are widely distributed in brain. Isoforms alpha-1 and alpha-2 are predominantly expressed in hippocampus, cerebral cortex, caudate-putamen, amygdala and the granule layer of the cerebellum. Alpha-1 is more abundant than alpha-2 in the periaqueductal region and the substantia nigra.1 Publication

Inductioni

In T-cells, following T-cell receptor (TCR) activation. Levels peak 48 hours after TCR and CD-28 costimulation.2 Publications

Gene expression databases

BgeeiENSMUSG00000020366.
CleanExiMM_MAPK9.
ExpressionAtlasiQ9WTU6. baseline and differential.
GenevisibleiQ9WTU6. MM.

Interactioni

Subunit structurei

Interacts with MECOM (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway (PubMed:11562351). Interacts with NFATC4 (By similarity). Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN (By similarity). Interacts with BCL10 (By similarity). Interacts with CTNNB1 and GSK3B (By similarity). Interacts with DCLK2 (PubMed:16628014). Interacts with MAPKBP1 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204972. 4 interactors.
DIPiDIP-31076N.
ELMiQ9WTU6.
IntActiQ9WTU6. 6 interactors.
MINTiMINT-1487632.
STRINGi10090.ENSMUSP00000020634.

Chemistry databases

BindingDBiQ9WTU6.

Structurei

3D structure databases

ProteinModelPortaliQ9WTU6.
SMRiQ9WTU6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 321Protein kinasePROSITE-ProRule annotationAdd BLAST296

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi183 – 185TXY3

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0665. Eukaryota.
ENOG410XSHI. LUCA.
GeneTreeiENSGT00550000074271.
HOVERGENiHBG014652.
InParanoidiQ9WTU6.
KOiK04440.
OMAiWEERNKN.
OrthoDBiEOG091G09G2.
PhylomeDBiQ9WTU6.
TreeFamiTF105100.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
PRINTSiPR01772. JNKMAPKINASE.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-2 (identifier: Q9WTU6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI
60 70 80 90 100
NVAVKKLSRP FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE
110 120 130 140 150
FQDVYLVMEL MDANLCQVIH MELDHERMSY LLYQMLCGIK HLHSAGIIHR
160 170 180 190 200
DLKPSNIVVK SDCTLKILDF GLARTACTNF MMTPYVVTRY YRAPEVILGM
210 220 230 240 250
GYKENVDIWS VGCIMAEMVL HKVLFPGRDY IDQWNKVIEQ LGTPSAEFMK
260 270 280 290 300
KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK
310 320 330 340 350
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE
360 370 380 390 400
EWKELIYKEV MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST
410 420
EHTLASDTDS SLDASTGPLE GCR
Length:423
Mass (Da):48,189
Last modified:February 21, 2001 - v2
Checksum:i0E759B486ABCE20D
GO
Isoform Alpha-1 (identifier: Q9WTU6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     377-423: DAAVSSKATPSQSSSINDISSMSTEHTLASDTDSSLDASTGPLEGCR → AQMQQ

Show »
Length:381
Mass (Da):44,078
Checksum:iD426C50349A526A4
GO
Isoform Beta-1 (identifier: Q9WTU6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     216-230: AEMVLHKVLFPGRDY → GELVKGCVIFQGTDH
     377-423: DAAVSSKATPSQSSSINDISSMSTEHTLASDTDSSLDASTGPLEGCR → AQMQQ

Show »
Length:381
Mass (Da):43,906
Checksum:iFCCB3C77B7B19C9D
GO
Isoform Beta-2 (identifier: Q9WTU6-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     216-230: AEMVLHKVLFPGRDY → GELVKGCVIFQGTDH

Show »
Length:423
Mass (Da):48,017
Checksum:iEE549B9F4F12F421
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti223V → C (PubMed:10674476).Curated1
Sequence conflicti237V → A in CAC88132 (PubMed:10674476).Curated1
Sequence conflicti386P → A in BAC27623 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004836216 – 230AEMVL…PGRDY → GELVKGCVIFQGTDH in isoform Beta-1 and isoform Beta-2. 3 PublicationsAdd BLAST15
Alternative sequenceiVSP_004837377 – 423DAAVS…LEGCR → AQMQQ in isoform Alpha-1 and isoform Beta-1. 2 PublicationsAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF052466 mRNA. Translation: AAD22576.1.
AF052467 mRNA. Translation: AAD22577.1.
AF052468 mRNA. Translation: AAD22578.1.
AF052469 mRNA. Translation: AAD22579.1.
AB005664 mRNA. Translation: BAA85876.1.
AJ315339
, AJ315340, AJ315341, AJ315342, AJ315343, AJ315344, AJ315345, AJ315346, AJ315347, AJ315348, AJ315349, AJ315350 Genomic DNA. Translation: CAC88132.1. Sequence problems.
AK031959 mRNA. Translation: BAC27623.1.
AL606479 Genomic DNA. Translation: CAI23940.1.
AL606479 Genomic DNA. Translation: CAI23941.1.
BC028341 mRNA. Translation: AAH28341.1.
CCDSiCCDS24623.1. [Q9WTU6-4]
CCDS24624.1. [Q9WTU6-2]
CCDS48782.1. [Q9WTU6-1]
CCDS48783.1. [Q9WTU6-3]
RefSeqiNP_001157143.1. NM_001163671.1. [Q9WTU6-1]
NP_001157144.1. NM_001163672.1. [Q9WTU6-3]
NP_058657.1. NM_016961.3. [Q9WTU6-2]
NP_997575.2. NM_207692.2. [Q9WTU6-4]
UniGeneiMm.68933.

Genome annotation databases

EnsembliENSMUST00000020634; ENSMUSP00000020634; ENSMUSG00000020366. [Q9WTU6-4]
ENSMUST00000043321; ENSMUSP00000042744; ENSMUSG00000020366. [Q9WTU6-1]
ENSMUST00000102778; ENSMUSP00000099839; ENSMUSG00000020366. [Q9WTU6-2]
ENSMUST00000109178; ENSMUSP00000104807; ENSMUSG00000020366. [Q9WTU6-3]
ENSMUST00000109179; ENSMUSP00000104808; ENSMUSG00000020366. [Q9WTU6-2]
ENSMUST00000164643; ENSMUSP00000132864; ENSMUSG00000020366. [Q9WTU6-3]
ENSMUST00000178543; ENSMUSP00000136977; ENSMUSG00000020366. [Q9WTU6-1]
GeneIDi26420.
KEGGimmu:26420.
UCSCiuc007ird.2. mouse. [Q9WTU6-2]
uc007irh.2. mouse. [Q9WTU6-1]
uc007iri.2. mouse. [Q9WTU6-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMK09_MOUSE
AccessioniPrimary (citable) accession number: Q9WTU6
Secondary accession number(s): Q5NCK9
, Q5NCL5, Q8C097, Q8VDD2, Q9WTU4, Q9WTU5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: September 27, 2017
This is version 175 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