Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Mitogen-activated protein kinase 8  

UniProtKB / Swiss-Prot ID :  MK08_HUMAN

Gene Name (Synonyms) : 
MAPK8, JNK1, PRKM8, SAPK1, SAPK1C  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. 

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 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. JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta- 2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. 

Protein Sequence MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRA...
Predicted Secondary Structure CCCCCCCCCCEEEEECCCCCCCCCCEEEEEEEEECCCEEEEEEEECCCCCEEEEEEECCHHCCHHHHHHH...
Protein Variant
LocationDescription
171G -> S (in a renal clear cell carcinomasample; somatic mutation).
177G -> R (in a glioblastoma multiformesample; somatic mutation).
365E -> K (in dbSNP:rs45483593). VAR_050592
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
116S-nitrosocysteineDANLCQVIQ
CCCHHHHCC
2.81dbSNO
Link
155Phosphoserine.DLKPSNIVV
ECCCCCEEE
37.29UniProtKB
Link
178PhosphothreonineRTAGTSFMM
EEECCCCEE
19.14Phosphositeplus
Link-
179PhosphoserineTAGTSFMMT
EECCCCEEE
15.38Phosphositeplus
Link-
183PhosphothreonineSFMMTPYVV
CCEEEEEEE
10.32Phosphositeplus
Link-
183PhosphothreonineSFMMTPYVV
CCEEEEEEE
10.32SysPTM
Link-
183Phosphothreonine (MAP2K7)SFMMTPYVV
CCEEEEEEE
10.32HPRD
Link-
183Phosphothreonine (MAP2K7;MAP2K7)SFMMTPYVV
CCEEEEEEE
10.32PhosphoELM
Link-
183Phosphothreonine; by MAP2K7.SFMMTPYVV
CCEEEEEEE
10.32UniProtKB
Link-
185PhosphotyrosineMMTPYVVTR
EEEEEEEEC
9.82Phosphositeplus
Link-
185PhosphotyrosineMMTPYVVTR
EEEEEEEEC
9.82SysPTM
Link-
185Phosphotyrosine (MAP2K4)MMTPYVVTR
EEEEEEEEC
9.82HPRD
Link-
185Phosphotyrosine (MAP2K7;MAP2K4;MAP2K4)MMTPYVVTR
EEEEEEEEC
9.82PhosphoELM
Link-
185Phosphotyrosine (RET)MMTPYVVTR
EEEEEEEEC
9.82HPRD
Link-
185Phosphotyrosine; by MAP2K4.MMTPYVVTR
EEEEEEEEC
9.82UniProtKB
Link-
188PhosphothreoninePYVVTRYYR
EEEEECCCC
11.69Phosphositeplus
Link-
255PhosphothreonineKLQPTVRTY
HHHHHHHHH
15.06HPRD
Link
255Phosphothreonine.KLQPTVRTY
HHHHHHHHH
15.06UniProtKB
Link
258PhosphothreoninePTVRTYVEN
HHHHHHHHH
27.81HPRD
Link
258Phosphothreonine.PTVRTYVEN
HHHHHHHHH
27.81UniProtKB
Link
259PhosphotyrosineTVRTYVENR
HHHHHHHHC
8.66HPRD
Link
259Phosphotyrosine.TVRTYVENR
HHHHHHHHC
8.66UniProtKB
Link
300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)DLLSKMLVI
HHHHHHHHC
35.90Phosphositeplus
Link
308N6-acetyllysineIDASKRISV
CCCCCCCCH
56.31HPRD
Link
308N6-acetyllysineIDASKRISV
CCCCCCCCH
56.31Phosphositeplus
Link
308N6-acetyllysine.IDASKRISV
CCCCCCCCH
56.31UniProtKB
Link
357PhosphotyrosineKELIYKEVM
HHHHHHHHH
17.45HPRD
Link
357Phosphotyrosine.KELIYKEVM
HHHHHHHHH
17.45UniProtKB
Link
367PhosphothreonineLEERTKNGV
HHCHHHHCC
31.94HPRD
Link-
367Phosphothreonine.LEERTKNGV
HHCHHHHCC
31.94UniProtKB
Link-
377PhosphoserineRGQPSPLGA
CCCCCCCCC
25.52HPRD
Link-
377PhosphoserineRGQPSPLGA
CCCCCCCCC
25.52HPRD
Link-
377PhosphoserineRGQPSPLGA
CCCCCCCCC
25.52PhosphoELM
Link-
377PhosphoserineRGQPSPLGA
CCCCCCCCC
25.52SysPTM
Link-
377Phosphoserine.RGQPSPLGA
CCCCCCCCC
25.52UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
P53_HUMANphysical interactionMINT-61312MINT15580310
JUN_HUMANphosphorylation reactionMINT-15587MINT8994040
JUN_HUMANphosphorylation reactionMINT-15461MINT8137421
BCLX_HUMANphosphorylation reactionMINT-56640MINT15733859
JUN_HUMANphysical interactionDIP:1061EDIP8137421
RASH_HUMANphysical interactionDIP:1062EDIP8137421
JUN_HUMANphosphorylationEBI-960011
intact16291755
STAT3_HUMANin vitro
in vivo
HPRD:03100HPRD11350938
10521505
9343414
10446219
12576423
14551213
9872331
12763138
CDN1A_HUMANin vitro
in vivo
HPRD:03100HPRD12058028
ATF2_HUMANin vitro
in vivo
HPRD:03100HPRD7737130
7737129
GSTP1_HUMANin vitro
in vivo
HPRD:03100HPRD12646564
11279197
GCR_HUMANin vitro
in vivo
HPRD:03100HPRD12351702
9199329
HSF1_HUMANin vitro
in vivo
HPRD:03100HPRD10747973
IRS1_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:03100HPRD12417588
11606564
10722755
12351658
K2C8_HUMANin vitro
in vivo
HPRD:03100HPRD11788583
11781324
9211903
CRK_HUMANin vitro
in vivo
HPRD:03100HPRD11432831
BCL2_HUMANin vivoHPRD:03100HPRD10567572
12039864
15225643
REL_HUMANin vivo
yeast 2-hybrid
HPRD:03100HPRD8621542
KU70_HUMANin vitro
in vivo
HPRD:03100HPRD11749722
JUNB_HUMANin vitro
in vivo
HPRD:03100HPRD9405416
9889198
8917518
JUND_HUMANin vitroHPRD:03100HPRD12052834
PAX2_HUMANin vitro
in vivo
HPRD:03100HPRD11700324
MAP1B_HUMANin vivoHPRD:03100HPRD12689591
P85A_HUMANin vivoHPRD:03100HPRD7642542
P53_HUMANin vitro
in vivo
HPRD:03100HPRD9732264
9393873
11283254
RASH_HUMANin vivoHPRD:03100HPRD8137421
11525649
MYC_HUMANin vitro
in vivo
HPRD:03100HPRD10551811
1748630
PRKDC_HUMANin vitro
in vivo
HPRD:03100HPRD11749722
MK14_HUMANin vivoHPRD:03100HPRD15778365
MK03_HUMANin vivoHPRD:03100HPRD15778365
JUN_HUMANin vivoHPRD:03100HPRD8137421
15302935
8654373
MK01_HUMANin vivoHPRD:03100HPRD15778365
ELK3_HUMANin vitroHPRD:03100HPRD11042694
PPARG_HUMANin vitro
in vivo
HPRD:03100HPRD9030579
PAXI_HUMANin vitro
in vivo
HPRD:03100HPRD12853963
BIM_HUMANin vitro
in vivo
HPRD:03100HPRD12591950
12818176
JIP1_HUMANin vitro
in vivo
HPRD:03100HPRD9733513
12756254
DUS1_HUMANyeast 2-hybridHPRD:03100HPRD11278799
EF2K_HUMANin vitroHPRD:03100HPRD12171600
BMF_HUMANin vitroHPRD:03100HPRD12591950
CSN2_HUMANin vivoHPRD:03100HPRD10585392
SMAD2_HUMANin vitro
in vivo
HPRD:03100HPRD15326485
BAD_HUMANin vitroHPRD:03100HPRD14967141
HSF4_HUMANin vitroHPRD:03100HPRD16581800
1433Z_HUMANin vivoHPRD:03100HPRD15696159
TNR1A_HUMANENSP00000353483STRING
GSTP1_HUMANENSP00000353483STRING
GA45B_HUMANENSP00000353483STRING
MK01_HUMANENSP00000353483STRING
TAB1_HUMANENSP00000353483STRING
PAI1_HUMANENSP00000353483STRING
CCL2_HUMANENSP00000353483STRING
DUS3_HUMANENSP00000353483STRING
IL2_HUMANENSP00000353483STRING
PAXI_HUMANENSP00000353483STRING
DUS16_HUMANENSP00000353483STRING
IL1R1_HUMANENSP00000353483STRING
DUS1_HUMANENSP00000353483STRING
TNF11_HUMANENSP00000353483STRING
EGR1_HUMANENSP00000353483STRING
DUS4_HUMANENSP00000353483STRING
DYL2_HUMANENSP00000353483STRING
JIP1_HUMANENSP00000353483STRING
DYL1_HUMANENSP00000353483STRING
CDN1A_HUMANENSP00000353483STRING
BMP4_HUMANENSP00000353483STRING
MKKS_HUMANENSP00000353483STRING
ELK1_HUMANENSP00000353483STRING
HSPB1_HUMANENSP00000353483STRING
RAC2_HUMANENSP00000353483STRING
INS_HUMANENSP00000353483STRING
INS_HUMANENSP00000353483STRING
RAF1_HUMANENSP00000353483STRING
JUND_HUMANENSP00000353483STRING
M3K10_HUMANENSP00000353483STRING
IL6_HUMANENSP00000353483STRING
P52K_HUMANENSP00000353483STRING
TAU_HUMANENSP00000353483STRING
MP2K4_HUMANENSP00000353483STRING
MP2K2_HUMANENSP00000353483STRING
MK03_HUMANENSP00000353483STRING
IL1A_HUMANENSP00000353483STRING
ATF2_HUMANENSP00000353483STRING
STAT3_HUMANENSP00000353483STRING
ICAM1_HUMANENSP00000353483STRING
M3K13_HUMANENSP00000353483STRING
M3K4_HUMANENSP00000353483STRING
TENA_HUMANENSP00000353483STRING
P53_HUMANENSP00000353483STRING
AKT1_HUMANENSP00000353483STRING
EGFR_HUMANENSP00000353483STRING
KPCA_HUMANENSP00000353483STRING
A4_HUMANENSP00000353483STRING
BAX_HUMANENSP00000353483STRING
M4K2_HUMANENSP00000353483STRING
VCAM1_HUMANENSP00000353483STRING
REL_HUMANENSP00000353483STRING
DUS7_HUMANENSP00000353483STRING
MAP1B_HUMANENSP00000353483STRING
CRK_HUMANENSP00000353483STRING
CRK_HUMANENSP00000353483STRING
DAPK3_HUMANENSP00000353483STRING
FADD_HUMANENSP00000353483STRING
MP2K1_HUMANENSP00000353483STRING
BCLX_HUMANENSP00000353483STRING
JUNB_HUMANENSP00000353483STRING
IRS1_HUMANENSP00000353483STRING
FOS_HUMANENSP00000353483STRING
IL8_HUMANENSP00000353483STRING
BAD_HUMANENSP00000353483STRING
M3K11_HUMANENSP00000353483STRING
RASH_HUMANENSP00000353483STRING
CASP3_HUMANENSP00000353483STRING
TF65_HUMANENSP00000353483STRING
TF65_HUMANENSP00000353483STRING
CDC42_HUMANENSP00000353483STRING
TRAF6_HUMANENSP00000353483STRING
VEGFA_HUMANENSP00000353483STRING
MYD88_HUMANENSP00000353483STRING
NOS2A_HUMANENSP00000353483STRING
SP1_HUMANENSP00000353483STRING
JIP2_HUMANENSP00000353483STRING
TRAF3_HUMANENSP00000353483STRING
HSF1_HUMANENSP00000353483STRING
FAK2_HUMANENSP00000353483STRING
SMAD3_HUMANENSP00000353483STRING
TRAF5_HUMANENSP00000353483STRING
IKKB_HUMANENSP00000353483STRING
M3K2_HUMANENSP00000353483STRING
ATF3_HUMANENSP00000353483STRING
E2F1_HUMANENSP00000353483STRING
CRKL_HUMANENSP00000353483STRING
TNR6_HUMANENSP00000353483STRING
BIM_HUMANENSP00000353483STRING
M3K5_HUMANENSP00000353483STRING
MP2K6_HUMANENSP00000353483STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-308, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, AND MASSSPECTROMETRY.
"Improved titanium dioxide enrichment of phosphopeptides from HeLacells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.";
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
J. Proteome Res. 6:4150-4162(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-255; THR-258; TYR-259;TYR-357 AND THR-367, AND MASS SPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, ANDMASS SPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND MASSSPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183; TYR-185 ANDSER-377, AND MASS SPECTROMETRY.
"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells.";
Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.;
J. Proteome Res. 8:3852-3861(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-155; THR-183; TYR-185AND SER-377, AND MASS SPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, ANDMASS SPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures