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Reviewed, UniProtKB/Swiss-Prot P45983 (MK08_HUMAN)

Last modified November 25, 2008. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Mitogen-activated protein kinase 8
    EC=2.7.11.24
Alternative name(s):
    Stress-activated protein kinase JNK1
    c-Jun N-terminal kinase 1
    JNK-46
Gene names
Name: MAPK8
Synonyms: JNK1, PRKM8
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. In T-cells, JNK1 and JNK2 are required for polarized differentiation of T-helper cells into Th1 cells By similarity. Phosphorylates heat shock factor protein 4 (HSF4).

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. Inhibited by dual specificity phosphatases, such as DUSP1.

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 RGNEF By similarity.

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, which activates the enzyme.

Sequence similarities

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

Contains 1 protein kinase domain.

Alternative products

This entry describes 4 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
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
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

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 residue1831Phosphothreonine
Modified residue1851Phosphotyrosine
Modified residue2551Phosphothreonine
Modified residue2581Phosphothreonine
Modified residue2591Phosphotyrosine
Modified residue3571Phosphotyrosine
Modified residue3671Phosphothreonine
Modified residue3771Phosphoserine

Natural variations

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 and isoform 3.
VSP_004833
Natural variant1711G → S in a renal clear cell carcinoma sample; somatic mutation.
VAR_042258
Natural variant1771G → R in a glioblastoma multiforme sample; somatic mutation.
VAR_042259

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 »

38444,229
Isoform 3 (JNK1-beta-1) [UniParc].

Checksum: 76E49A950E64C1A1
Show »

38444,022
Isoform 4 (JNK1-beta-2) [UniParc].

Checksum: 3F5CC3F6A4F3EF2D
Show »

42748,088

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: 8137421] [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: 8654373] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain.
[3]"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: 7839144] [Abstract]
Cited for: MUTAGENESIS.
[4]"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: 11062067] [Abstract]
Cited for: REGULATION BY MAP2K4 AND MAP2K7, COFACTOR.
[5]"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: 12514174] [Abstract]
Cited for: INTERACTION WITH WWOX AND TP53.
[6]"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: 15693750] [Abstract]
Cited for: INTERACTION WITH SPAG9.
[7]"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: 16581800] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HSF4.
[8]"Global survey of phosphotyrosine signaling identifies oncogenic kinases 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. expand/collapse author list , 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) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, MASS SPECTROMETRY.
Tissue: Lung.
[9]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells 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) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-255; THR-258; TYR-259; TYR-357 AND THR-367, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"Proteomics analysis of protein kinases by target class-selective prefractionation 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) [PubMed: 17192257] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY.
[11]"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: 18307971] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF JDP2.
[12]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCA