MAPK9 (mitogen-activated protein kinase 9)

Gene

• Entrez ID: 5601
• Gene name: Mitogen-activated protein kinase 9
• Gene symbol: MAPK9
• Synonyms: JNK-55, JNK2, JNK2A, JNK2ALPHA, JNK2B, JNK2BETA, PRKM9, SAPK, SAPK1a, p54a, p54aSAPK
• Chromosome: 5
• Chromosome location: 5q35.3
• Summary: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene`s mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Sep 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003240	hsa-miR-93-5p	Luciferase reporter assay	20065103
MIRT003982	hsa-miR-199a-3p	Western blot	18456660
MIRT004359	hsa-miR-17-5p	qRT-PCR, Luciferase reporter assay, Western blot	18700987
MIRT004359	hsa-miR-17-5p	Luciferase reporter assay	21283765
MIRT004359	hsa-miR-17-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	23029228
MIRT005856	hsa-miR-20a-5p	Luciferase reporter assay	21283765
MIRT005864	hsa-miR-106b-5p	Luciferase reporter assay	21283765
MIRT021647	hsa-miR-141-3p	Western blot	20053927
MIRT024284	hsa-miR-215-5p	Microarray	19074876
MIRT025800	hsa-miR-7-5p	Sequencing	20371350
MIRT026550	hsa-miR-192-5p	Microarray	19074876
MIRT046207	hsa-miR-27b-3p	CLASH	23622248
MIRT049753	hsa-miR-92a-3p	CLASH	23622248
MIRT054220	hsa-miR-20b-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	23029228
MIRT054221	hsa-miR-106a-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	23029228
MIRT313265	hsa-miR-1178-3p	PAR-CLIP	22100165
MIRT448677	hsa-miR-4635	PAR-CLIP	22100165
MIRT448678	hsa-miR-6765-3p	PAR-CLIP	22100165
MIRT448679	hsa-miR-3622b-3p	PAR-CLIP	22100165
MIRT448680	hsa-miR-3622a-3p	PAR-CLIP	22100165
MIRT448681	hsa-miR-203a-3p	PAR-CLIP	22100165

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004705	Function	JUN kinase activity	IBA	21873635
GO:0004705	Function	JUN kinase activity	IDA	8654373
GO:0004707	Function	MAP kinase activity	IBA	21873635
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	10376527, 15158451, 16189514, 16288922, 19060904, 20871632, 21516116, 21988832, 25241761, 25416956, 28089251, 29892012, 31515488, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IMP	22441692
GO:0007254	Process	JNK cascade	IBA	21873635
GO:0007254	Process	JNK cascade	IDA	8654373
GO:0007254	Process	JNK cascade	TAS
GO:0007258	Process	JUN phosphorylation	IEA
GO:0008134	Function	Transcription factor binding	IDA	10376527
GO:0010628	Process	Positive regulation of gene expression	IMP	18262097
GO:0010744	Process	Positive regulation of macrophage derived foam cell differentiation	IMP	18262097
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	21856198
GO:0031398	Process	Positive regulation of protein ubiquitination	IEA
GO:0034614	Process	Cellular response to reactive oxygen species	IMP	26514923
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0048511	Process	Rhythmic process	IEA
GO:0051090	Process	Regulation of DNA-binding transcription factor activity	TAS
GO:0061833	Process	Protein localization to tricellular tight junction	IEA
GO:0071276	Process	Cellular response to cadmium ion	IMP	26514923
GO:0071803	Process	Positive regulation of podosome assembly	IEA
GO:1901485	Process	Positive regulation of transcription factor catabolic process	IEA
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IEA

Other IDs

• MIM: 602896
• HGNC: 6886
• e!Ensembl: ENSG00000050748

Protein

• UniProt ID: P45984
• Protein name: Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2)
• Protein function: 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). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). ; MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.
• PDB: 3E7O, 3NPC, 7CML
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	26 → 321	Protein kinase domain	Domain

• Sequence:

  MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRP
  FQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIH
  MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNF
  MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQ
  LGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSK
  MLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEV
  MDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPL
  EGCR

• Sequence length: 424