CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007764
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mitogen-activated protein kinase 8 
Protein Synonyms/Alias
 MAP kinase 8; MAPK 8; JNK-46; Stress-activated protein kinase 1c; SAPK1c; Stress-activated protein kinase JNK1; c-Jun N-terminal kinase 1 
Gene Name
 MAPK8 
Gene Synonyms/Alias
 JNK1; PRKM8; SAPK1; SAPK1C 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
30LKRYQNLKPIGSGAQubiquitination[1]
68FQNQTHAKRAYRELVubiquitination[1]
153GIIHRDLKPSNIVVKubiquitination[1]
160KPSNIVVKSDCTLKIubiquitination[1]
166VKSDCTLKILDFGLAubiquitination[1]
251PCPEFMKKLQPTVRTubiquitination[1]
265TYVENRPKYAGYSFEubiquitination[1]
288PADSEHNKLKASQARubiquitination[1]
290DSEHNKLKASQARDLubiquitination[1]
300QARDLLSKMLVIDASubiquitination[1, 2]
308MLVIDASKRISVDEAacetylation[3, 4]
308MLVIDASKRISVDEAubiquitination[1, 5]
Reference
 [1] 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]
 [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] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. 
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.
 MOD_RES 377 377 Phosphoserine (By similarity).  
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
 427 AA 
Protein Sequence
MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 60
FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 120
MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 180
MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ 240
LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 300
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 360
MDLEERTKNG VIRGQPSPLG AAVINGSQHP SSSSSVNDVS SMSTDPTLAS DTDSSLEAAA 420
GPLGCCR 427 
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:0035033; F:histone deacetylase regulator activity; IMP:BHF-UCL.
 GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
 GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0001503; P:ossification; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
 GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Compara.
 GO:0090045; P:positive regulation of deacetylase activity; IMP:BHF-UCL.
 GO:2000017; P:positive regulation of determination of dorsal identity; IEA:Compara.
 GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
 GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome.
 GO:0046686; P:response to cadmium ion; IEA:Compara.
 GO:0009411; P:response to UV; IDA:MGI.
 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.