Mitogen-activated protein kinase 9

Details

Name
Mitogen-activated protein kinase 9
Synonyms
  • 2.7.11.24
  • c-Jun N-terminal kinase 2
  • JNK-55
  • JNK2
  • MAP kinase 9
  • MAPK 9
  • PRKM9
  • SAPK1A
  • Stress-activated protein kinase 1a
  • Stress-activated protein kinase JNK2
Gene Name
MAPK9
UniProtKB Entry
P45984Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0007238|Mitogen-activated protein kinase 9
MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRP
FQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIH
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNF
MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQ
LGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSK
MLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEV
MDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPL
EGCR
Number of residues
424
Molecular Weight
48138.655
Theoretical pI
5.34
GO Classification
Functions
protein serine kinase activity / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity
Processes
apoptotic signaling pathway / cellular response to cadmium ion / cellular response to reactive oxygen species / cellular senescence / inflammatory response to wounding / modulation of chemical synaptic transmission / positive regulation of cytokine production involved in inflammatory response / positive regulation of podosome assembly / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein ubiquitination / protein localization to tricellular tight junction
Components
cytoplasm / nuclear speck / nucleus / plasma membrane / Schaffer collateral - CA1 synapse
General Function
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). Extracellular stimuli such as pro-inflammatory 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 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). 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 (PubMed:10376527). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929). Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929). Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674). Participates also in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-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 proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021865|Mitogen-activated protein kinase 9 (MAPK9)
ATGAGCGACAGTAAATGTGACAGTCAGTTTTATAGTGTGCAAGTGGCAGACTCAACCTTC
ACTGTCCTAAAACGTTACCAGCAGCTGAAACCAATTGGCTCTGGGGCCCAAGGGATTGTT
TGTGCTGCATTTGATACAGTTCTTGGGATAAATGTTGCAGTCAAGAAACTAAGCCGTCCT
TTTCAGAACCAAACTCATGCAAAGAGAGCTTATCGTGAACTTGTCCTCTTAAAATGTGTC
AATCATAAAAATATAATTAGTTTGTTAAATGTGTTTACACCACAAAAAACTCTAGAAGAA
TTTCAAGATGTGTATTTGGTTATGGAATTAATGGATGCTAACTTATGTCAGGTTATTCAC
ATGGAGCTGGATCATGAAAGAATGTCCTACCTTCTTTACCAGATGCTTTGTGGTATTAAA
CATCTGCATTCAGCTGGTATAATTCATAGAGATTTGAAGCCTAGCAACATTGTTGTGAAA
TCAGACTGCACCCTGAAGATCCTTGACTTTGGCCTGGCCCGGACAGCGTGCACTAACTTC
ATGATGACCCCTTACGTGGTGACACGGTACTACCGGGCGCCCGAAGTCATCCTGGGTATG
GGCTACAAAGAGAACGTTGATATCTGGTCAGTGGGTTGCATCATGGGAGAGCTGGTGAAA
GGTTGTGTGATATTCCAAGGCACTGACCGTATCCTTCCCCGCGACCTTGGCCCCGCCATG
CTTTCTTAA
Chromosome Location
5
Locus
5q35.3
External Identifiers
ResourceLink
UniProtKB IDP45984
UniProtKB Entry NameMK09_HUMAN
GenBank Protein ID598183
GenBank Gene IDL31951
GeneCard IDMAPK9
HGNC IDHGNC:6886
PDB ID(s)3E7O, 3NPC, 7CML, 7N8T, 8ELC
KEGG IDhsa:5601
IUPHAR/Guide To Pharmacology ID1497
NCBI Gene ID5601
General References
  1. Sluss HK, Barrett T, Derijard B, Davis RJ: Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol Cell Biol. 1994 Dec;14(12):8376-84. [Article]
  2. Kallunki T, Su B, Tsigelny I, Sluss HK, Derijard B, Moore G, Davis R, Karin M: JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev. 1994 Dec 15;8(24):2996-3007. [Article]
  3. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 1996 Jun 3;15(11):2760-70. [Article]
  4. Wang P, Xiong Y, Ma C, Shi T, Ma D: Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1. BMB Rep. 2010 Nov;43(11):738-43. doi: 10.5483/BMBRep.2010.43.11.738. [Article]
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  12. Mayer C, Bierhoff H, Grummt I: The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 2005 Apr 15;19(8):933-41. Epub 2005 Apr 1. [Article]
  13. Yao K, Cho YY, Bergen HR 3rd, Madden BJ, Choi BY, Ma WY, Bode AM, Dong Z: Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation. Cancer Res. 2007 Sep 15;67(18):8725-35. [Article]
  14. Blonska M, Pappu BP, Matsumoto R, Li H, Su B, Wang D, Lin X: The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway. Immunity. 2007 Jan;26(1):55-66. Epub 2006 Dec 28. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Mitogen-activated protein kinase 9 (Humans)protein
primary
Mitogen-activated Protein Kinases (Humans)protein
c-Jun N-terminal kinases (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
N-{3-[5-(1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl]phenyl}furan-2-carboxamideexperimentalunknowntargetDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails
Encorafenibapproved, investigationalyestargetinhibitorDetails
PyrazolanthroneexperimentalyestargetinhibitorDetails
CC-401investigationalyestargetmodulatorDetails
TanzisertibinvestigationalyestargetmodulatorDetails
NP-51investigationalyestargetinhibitorDetails
D-JNKI-1investigationalyestargetmodulatorDetails
Minocyclineapproved, investigationalunknowntargetinhibitorDetails
HalicinexperimentalunknowntargetinhibitorDetails