CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007765
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mitogen-activated protein kinase 9 
Protein Synonyms/Alias
 MAP kinase 9; MAPK 9; JNK-55; Stress-activated protein kinase 1a; SAPK1a; Stress-activated protein kinase JNK2; c-Jun N-terminal kinase 2 
Gene Name
 MAPK9 
Gene Synonyms/Alias
 JNK2; PRKM9; SAPK1A 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
250TPSAEFMKKLQPTVRacetylation[1]
250TPSAEFMKKLQPTVRubiquitination[2]
300QARDLLSKMLVIDPDubiquitination[3]
353EHAIEEWKELIYKEVubiquitination[4, 5]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 26 321 Protein kinase.
 NP_BIND 32 40 ATP (By similarity).
 MOTIF 183 185 TXY.
 ACT_SITE 151 151 Proton acceptor (By similarity).
 BINDING 55 55 ATP (By similarity).
 MOD_RES 183 183 Phosphothreonine; by MAP2K7.
 MOD_RES 185 185 Phosphotyrosine; by MAP2K4.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 424 AA 
Protein Sequence
MSDSKCDSQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP 60
FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH 120
MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF 180
MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ 240
LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK 300
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV 360
MDWEERSKNG VVKDQPSDAA VSSNATPSQS SSINDISSMS TEQTLASDTD SSLDASTGPL 420
EGCR 424 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IEA:Compara.
 GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
 GO:0008134; F:transcription factor binding; IDA:UniProtKB.
 GO:0071363; P:cellular response to growth factor stimulus; IEA:Compara.
 GO:0071347; P:cellular response to interleukin-1; IEA:Compara.
 GO:0071222; P:cellular response to lipopolysaccharide; IEA:Compara.
 GO:0071356; P:cellular response to tumor necrosis factor; IEA:Compara.
 GO:0034644; P:cellular response to UV; IEA:Compara.
 GO:0007417; P:central nervous system development; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0031175; P:neuron projection development; IEA:Compara.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Compara.
 GO:0010770; P:positive regulation of cell morphogenesis involved in differentiation; IEA:Compara.
 GO:0032722; P:positive regulation of chemokine production; IEA:Compara.
 GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
 GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Compara.
 GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Compara.
 GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Compara.
 GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Compara.
 GO:0001934; P:positive regulation of protein phosphorylation; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0006626; P:protein targeting to mitochondrion; IEA:Compara.
 GO:0046328; P:regulation of JNK cascade; IEA:Compara.
 GO:0031396; P:regulation of protein ubiquitination; IEA:Compara.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome.
 GO:0001836; P:release of cytochrome c from mitochondria; IEA:Compara.
 GO:0014075; P:response to amine stimulus; IEA:Compara.
 GO:0046686; P:response to cadmium ion; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR003527; MAP_kinase_CS.
 IPR008351; MAPK_JNK.
 IPR000719; Prot_kinase_cat_dom.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS01351; MAPK
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS
 PR01772; JNKMAPKINASE.