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P45983 (MK08_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 8

Short name=MAP kinase 8
Short name=MAPK 8
EC=2.7.11.24
Alternative name(s):
JNK-46
Stress-activated protein kinase 1c
Short name=SAPK1c
Stress-activated protein kinase JNK1
c-Jun N-terminal kinase 1
Gene names
Name:MAPK8
Synonyms:JNK1, PRKM8, SAPK1, SAPK1C
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.13 Ref.16 Ref.17 Ref.18 Ref.23 Ref.24 Ref.27 Ref.29

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. Ref.13 Ref.16 Ref.17 Ref.18 Ref.23 Ref.24 Ref.27 Ref.29

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium. Ref.9

Enzyme regulation

Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3. Ref.21

Subunit structure

Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX. Interacts with JAMP. Forms a complex with MAPK8IP1 and ARHGEF28 By similarity. Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells By similarity. Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.21 Ref.26

Subcellular location

Cytoplasm. Nucleus Ref.28.

Domain

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Post-translational modification

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2. Ref.9 Ref.15

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
S-nitrosylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

JNK cascade

Inferred from direct assay Ref.2. Source: UniProtKB

JUN phosphorylation

Inferred from direct assay Ref.27. Source: UniProtKB

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cellular response to lipopolysaccharide

Inferred from direct assay PubMed 23776175. Source: MGI

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from direct assay Ref.27. Source: UniProtKB

negative regulation of protein binding

Inferred from direct assay Ref.27. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

ossification

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from direct assay Ref.27. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay Ref.27. Source: UniProtKB

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of deacetylase activity

Inferred from mutant phenotype Ref.23. Source: BHF-UCL

positive regulation of determination of dorsal identity

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from mutant phenotype PubMed 22065586. Source: BHF-UCL

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

regulation of histone deacetylation

Inferred from mutant phenotype Ref.23. Source: GOC

regulation of protein localization

Inferred from direct assay Ref.23. Source: BHF-UCL

regulation of sequence-specific DNA binding transcription factor activity

Traceable author statement. Source: Reactome

response to UV

Inferred from direct assay PubMed 14967141. Source: MGI

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to stress

Traceable author statement Ref.1. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.23. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase activity

Inferred from direct assay Ref.27Ref.2. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction Ref.23. Source: BHF-UCL

histone deacetylase regulator activity

Inferred from mutant phenotype Ref.23. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 16533805. Source: IntAct

protein serine/threonine kinase activity

Inferred from direct assay Ref.23Ref.27. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P45983-1)

Also known as: JNK1-alpha-2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: P45983-2)

Also known as: JNK1-alpha-1;

The sequence of this isoform differs from the canonical sequence as follows:
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ
Note: Contains a phosphoserine at position 377.
Isoform 3 (identifier: P45983-3)

Also known as: JNK1-beta-1;

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ
Note: Contains a phosphoserine at position 377.
Isoform 4 (identifier: P45983-4)

Also known as: JNK1-beta-2;

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH
Isoform 5 (identifier: P45983-5)

The sequence of this isoform differs from the canonical sequence as follows:
     206-281: Missing.
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427Mitogen-activated protein kinase 8
PRO_0000186262

Regions

Domain26 – 321296Protein kinase
Nucleotide binding32 – 409ATP By similarity
Motif183 – 1853TXY

Sites

Active site1511Proton acceptor By similarity
Binding site551ATP By similarity

Amino acid modifications

Modified residue1161S-nitrosocysteine By similarity
Modified residue1831Phosphothreonine; by MAP2K7 Ref.9
Modified residue1851Phosphotyrosine; by MAP2K4 Ref.9
Modified residue3771Phosphoserine By similarity

Natural variations

Alternative sequence206 – 28176Missing in isoform 5.
VSP_054554
Alternative sequence2081L → I in isoform 3 and isoform 4.
VSP_004831
Alternative sequence219 – 23012VCHKI…PGRDY → IKGGVLFPGTDH in isoform 3 and isoform 4.
VSP_004832
Alternative sequence380 – 42748GAAVI…LGCCR → AQVQQ in isoform 1, isoform 3 and isoform 5.
VSP_004833
Natural variant1711G → S in a renal clear cell carcinoma sample; somatic mutation. Ref.31
VAR_042258
Natural variant1771G → R in a glioblastoma multiforme sample; somatic mutation. Ref.31
VAR_042259
Natural variant3651E → K.
Corresponds to variant rs45483593 [ dbSNP | Ensembl ].
VAR_050592

Experimental info

Mutagenesis1831T → A: Phosphorylation blocked.
Mutagenesis1851Y → F: Phosphorylation blocked.

Secondary structure

......................................................................... 427
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (JNK1-alpha-2) [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 94FB6BE0358B9B60

FASTA42748,296
        10         20         30         40         50         60 
MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 

        70         80         90        100        110        120 
FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 

       130        140        150        160        170        180 
MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 

       190        200        210        220        230        240 
MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ 

       250        260        270        280        290        300 
LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 

       310        320        330        340        350        360 
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 

       370        380        390        400        410        420 
MDLEERTKNG VIRGQPSPLG AAVINGSQHP SSSSSVNDVS SMSTDPTLAS DTDSSLEAAA 


GPLGCCR 

« Hide

Isoform 1 (JNK1-alpha-1) [UniParc].

Checksum: A7320EF933E9CF85
Show »

FASTA38444,229
Isoform 3 (JNK1-beta-1) [UniParc].

Checksum: 76E49A950E64C1A1
Show »

FASTA38444,022
Isoform 4 (JNK1-beta-2) [UniParc].

Checksum: 3F5CC3F6A4F3EF2D
Show »

FASTA42748,088
Isoform 5 [UniParc].

Checksum: 914B803A1223601D
Show »

FASTA30835,333

References

« Hide 'large scale' references
[1]"JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain."
Derijard B., Hibi M., Wu I.-H., Barrett T., Su B., Deng T., Karin M., Davis R.J.
Cell 76:1025-1037(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"Selective interaction of JNK protein kinase isoforms with transcription factors."
Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., Derijard B., Davis R.J.
EMBO J. 15:2760-2770(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain.
[3]Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Tang Z., Huang B., Li H., Yang S.
Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[8]"Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms."
Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J.
Science 267:682-685(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[9]"Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7."
Fleming Y., Armstrong C.G., Morrice N., Paterson A., Goedert M., Cohen P.
Biochem. J. 352:145-154(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-183 AND TYR-185, REGULATION BY MAP2K4 AND MAP2K7, COFACTOR.
[10]"The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death."
Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H.
EMBO J. 19:2958-2968(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MECOM.
[11]"JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis."
Chang N.-S., Doherty J., Ensign A.
J. Biol. Chem. 278:9195-9202(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWOX AND TP53.
[12]"Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein."
Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., Herr J.C., Okumura K., Hasegawa A., Koyama K., Suri A.
Biochem. J. 389:73-82(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPAG9.
[13]"Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26."
Hu Y., Mivechi N.F.
Mol. Cell. Biol. 26:3282-3294(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HSF4.
[14]"Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation."
Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y., Bode A.M., Dong Z.
Cancer Res. 67:8725-8735(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFATC4.
[15]"Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis. JNK-and caspase-dependent nuclear localization is a requirement for membrane blebbing."
Zihni C., Mitsopoulos C., Tavares I.A., Baum B., Ridley A.J., Morris J.D.
J. Biol. Chem. 282:6484-6493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY TAOK2.
[16]"Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to activation of the transcription factor Elk-1."
Zhang L., Yang S.H., Sharrocks A.D.
Mol. Cell. Biol. 27:2861-2869(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ELK1.
[17]"Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in Escherichia coli by Jun N-terminal kinase 1."
Murata T., Shinozuka Y., Obata Y., Yokoyama K.K.
Anal. Biochem. 376:115-121(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF JDP2.
[18]"JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy."
Wei Y., Pattingre S., Sinha S., Bassik M., Levine B.
Mol. Cell 30:678-688(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BCL2.
[19]"Kinase-selective enrichment enables quantitative phosphoproteomics of the 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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Crystal structure of SCCA1 and insight about the interaction with JNK1."
Zheng B., Matoba Y., Kumagai T., Katagiri C., Hibino T., Sugiyama M.
Biochem. Biophys. Res. Commun. 380:143-147(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SERPINB3, ENZYME REGULATION.
[22]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity."
Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R., Bordone L.
PLoS ONE 4:E8414-E8414(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SIRT1.
[24]"JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis."
Tomlinson V., Gudmundsdottir K., Luong P., Leung K.Y., Knebel A., Basu S.
Cell Death Dis. 1:E29-E29(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF YAP1.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"A critical step for JNK activation: isomerization by the prolyl isomerase Pin1."
Park J.E., Lee J.A., Park S.G., Lee D.H., Kim S.J., Kim H.J., Uchida C., Uchida T., Park B.C., Cho S.
Cell Death Differ. 19:153-161(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIN1.
[27]"Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin-dependent cells."
Deng H., Zhang J., Yoon T., Song D., Li D., Lin A.
Int. J. Biochem. Cell Biol. 43:409-415(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[28]"Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis."
Wang J., Tang R., Lv M., Wang Q., Zhang X., Guo Y., Chang H., Qiao C., Xiao H., Li X., Li Y., Shen B., Zhang J.
Mol. Biol. Cell 22:117-127(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[29]"JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress."
Miotto B., Struhl K.
Mol. Cell 44:62-71(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDT1.
[30]"Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125."
Heo Y.S., Kim S.K., Seo C.I., Kim Y.K., Sung B.J., Lee H.S., Lee J.I., Park S.Y., Kim J.H., Hwang K.Y., Hyun Y.L., Jeon Y.H., Ro S., Cho J.M., Lee T.G., Yang C.H.
EMBO J. 23:2185-2195(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-363.
[31]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-171 AND ARG-177.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26318 mRNA. Translation: AAA36131.1.
U34822 mRNA. Translation: AAC50607.1.
U35004 mRNA. Translation: AAC50610.1.
U35005 mRNA. Translation: AAC50611.1.
DQ234352 mRNA. Translation: ABB29981.1.
AC016397 Genomic DNA. No translation available.
AC074325 Genomic DNA. No translation available.
AB451231 mRNA. Translation: BAG70045.1.
CH471187 Genomic DNA. Translation: EAW93132.1.
CH471187 Genomic DNA. Translation: EAW93129.1.
CH471187 Genomic DNA. Translation: EAW93130.1.
CH471187 Genomic DNA. Translation: EAW93133.1.
CH471187 Genomic DNA. Translation: EAW93134.1.
CH471187 Genomic DNA. Translation: EAW93136.1.
BC144063 mRNA. Translation: AAI44064.1.
CCDSCCDS7223.1. [P45983-4]
CCDS7224.1. [P45983-1]
CCDS7225.1. [P45983-2]
CCDS7226.1. [P45983-3]
PIRS71097.
S71099.
RefSeqNP_001265476.1. NM_001278547.1. [P45983-4]
NP_001265477.1. NM_001278548.1. [P45983-5]
NP_002741.1. NM_002750.3. [P45983-2]
NP_620634.1. NM_139046.2. [P45983-3]
NP_620637.1. NM_139049.2. [P45983-1]
XP_006717980.1. XM_006717917.1. [P45983-1]
XP_006717981.1. XM_006717918.1. [P45983-3]
XP_006717982.1. XM_006717919.1. [P45983-2]
UniGeneHs.138211.
Hs.522924.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UKHX-ray2.35A1-363[»]
1UKIX-ray2.70A1-363[»]
2G01X-ray3.50A/B1-364[»]
2GMXX-ray3.50A/B1-364[»]
2H96X-ray3.00A/B1-364[»]
2NO3X-ray3.20A/B1-364[»]
2XRWX-ray1.33A2-364[»]
2XS0X-ray2.60A1-379[»]
3ELJX-ray1.80A1-364[»]
3O17X-ray3.00A/B1-364[»]
3O2MX-ray2.70A/B1-364[»]
3PZEX-ray2.00A7-364[»]
3V3VX-ray2.70A1-366[»]
3VUDX-ray3.50A1-364[»]
3VUGX-ray3.24A1-364[»]
3VUHX-ray2.70A1-364[»]
3VUIX-ray2.80A1-364[»]
3VUKX-ray2.95A1-364[»]
3VULX-ray2.81A1-364[»]
3VUMX-ray2.69A1-364[»]
4AWIX-ray1.91A1-364[»]
4E73X-ray2.27A1-363[»]
4G1WX-ray2.45A1-363[»]
4HYSX-ray2.42A1-363[»]
4HYUX-ray2.15A1-363[»]
4IZYX-ray2.30A1-363[»]
4L7FX-ray1.95A7-362[»]
ProteinModelPortalP45983.
SMRP45983. Positions 7-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111585. 142 interactions.
DIPDIP-249N.
IntActP45983. 46 interactions.
MINTMINT-1211982.
STRING9606.ENSP00000353483.

Chemistry

BindingDBP45983.
ChEMBLCHEMBL2096667.
GuidetoPHARMACOLOGY1496.

PTM databases

PhosphoSiteP45983.

Polymorphism databases

DMDM2507195.

Proteomic databases

MaxQBP45983.
PaxDbP45983.
PRIDEP45983.

Protocols and materials databases

DNASU5599.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360332; ENSP00000353483; ENSG00000107643. [P45983-1]
ENST00000374176; ENSP00000363291; ENSG00000107643. [P45983-4]
ENST00000374179; ENSP00000363294; ENSG00000107643. [P45983-3]
ENST00000374182; ENSP00000363297; ENSG00000107643. [P45983-2]
ENST00000374189; ENSP00000363304; ENSG00000107643. [P45983-1]
ENST00000395611; ENSP00000378974; ENSG00000107643.
GeneID5599.
KEGGhsa:5599.
UCSCuc001jgo.3. human. [P45983-3]
uc001jgp.3. human. [P45983-1]
uc001jgq.3. human. [P45983-2]

Organism-specific databases

CTD5599.
GeneCardsGC10P049514.
HGNCHGNC:6881. MAPK8.
HPACAB004463.
MIM601158. gene.
neXtProtNX_P45983.
PharmGKBPA283.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG014652.
InParanoidP45983.
KOK04440.
OMAREHTLEQ.
OrthoDBEOG7PCJGV.
PhylomeDBP45983.
TreeFamTF105100.

Enzyme and pathway databases

BRENDA2.7.11.24. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_120956. Cellular responses to stress.
REACT_578. Apoptosis.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP45983.

Gene expression databases

ArrayExpressP45983.
BgeeP45983.
CleanExHS_MAPK8.
GenevestigatorP45983.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01772. JNKMAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP45983.
GeneWikiMAPK8.
GenomeRNAi5599.
NextBio21738.
PROP45983.
SOURCESearch...

Entry information

Entry nameMK08_HUMAN
AccessionPrimary (citable) accession number: P45983
Secondary accession number(s): B5BTZ5 expand/collapse secondary AC list , B7ZLV4, D3DX88, D3DX92, Q15709, Q15712, Q15713, Q308M2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM