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Reviewed, UniProtKB/Swiss-Prot P49185 (MK08_RAT)

Last modified October 13, 2009. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · 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
    SAPK gamma
    p54 gamma
Gene names
Name: Mapk8
Synonyms: Jnk1, Prkm8
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length411 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. Phosphorylates heat shock factor protein 4 (HSF4) By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium. Ref.2

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 By similarity. Inhibited by IFN-gamma-induced S-nitrosylation.

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, WWOX and JAMP. Interacts with NFATC4 By similarity. Forms a complex with MAPK8IP1 and RGNEF.

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 By similarity.

Nitrosylated upon IFN-gamma-induced endogenous NO production, which inhibits the enzyme.

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
S-nitrosylation
Gene Ontology (GO)
   Biological processinflammatory response

Inferred from direct assay. Source: RGD

negative regulation of apoptosis

Inferred from direct assay. Source: RGD

neuron projection development

Inferred from mutant phenotype. Source: RGD

positive regulation of DNA replication

Inferred from mutant phenotype. Source: RGD

positive regulation of cell migration

Inferred from direct assay. Source: RGD

positive regulation of microtubule polymerization

Inferred from mutant phenotype. Source: RGD

regulation of transcription, DNA-dependent

Inferred from direct assay. Source: RGD

response to heat

Inferred from direct assay. Source: RGD

response to hydrogen peroxide

Inferred from direct assay. Source: RGD

response to osmotic stress

Inferred from direct assay. Source: RGD

response to steroid hormone stimulus

Inferred from expression pattern. Source: RGD

   Cellular componentaxon part

Inferred from direct assay. Source: RGD

cytosol

Inferred from Experiment. Source: Reactome

dendrite cytoplasm

Inferred from direct assay. Source: RGD

mitochondrion

Inferred from direct assay. Source: RGD

nucleus

Inferred from direct assay. Source: RGD

perikaryon

Inferred from direct assay. Source: RGD

vesicle

Inferred from direct assay. Source: RGD

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Mitogen-activated protein kinase 8
PRO_0000186264

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; in inhibited form
Modified residue1831Phosphothreonine By similarity
Modified residue1851Phosphotyrosine By similarity
Modified residue2551Phosphothreonine By similarity
Modified residue2581Phosphothreonine By similarity
Modified residue2591Phosphotyrosine By similarity
Modified residue3081N6-acetyllysine By similarity
Modified residue3571Phosphotyrosine By similarity
Modified residue3671Phosphothreonine By similarity
Modified residue3771Phosphoserine By similarity

Experimental info

Mutagenesis1161C → S: Abolished inhibitory effect of IFN-gamma on JNK1 activity. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P49185-1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 04E388B4F94633D4

FASTA41146,807
        10         20         30         40         50         60 
MSRSKRDNNF YSVEIADSTF 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 LKILFPGRDY 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 
MDLEERTKNG VIRGQPSPLG AAVINGSQHP VSSPSVNDMS SMSTDPTLAS D 

« Hide

References

[1]"The stress-activated protein kinase subfamily of c-Jun kinases."
Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Rubie E.A., Ahmad M.F., Avruch J., Woodgett J.R.
Nature 369:156-160(1994) [PubMed: 8177321] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Stimulation of 'stress-regulated' mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses."
Clerk A., Fuller S.J., Michael A., Sugden P.H.
J. Biol. Chem. 273:7228-7234(1998) [PubMed: 9516415] [Abstract]
Cited for: FUNCTION, COFACTOR.
Tissue: Heart.
[3]"Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation."
Park H.S., Huh S.H., Kim M.S., Lee S.H., Choi E.J.
Proc. Natl. Acad. Sci. U.S.A. 97:14382-14387(2000) [PubMed: 11121042] [Abstract]
Cited for: S-NITROSYLATION AT CYS-116, MUTAGENESIS OF CYS-116.
[4]"Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity to an EGFP-tagged protein."
Wu J., Zhai J., Lin H., Nie Z., Ge W.-W., Garcia-Bermejo L., Muschel R.J., Schlaepfer W.W., Canete-Soler R.
Brain Res. Mol. Brain Res. 117:27-38(2003) [PubMed: 14499478] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND RGNEF.
+Additional computationally mapped references.

Cross-references

Sequence databases

L27129 mRNA. Translation: AAA42111.1.
IPIIPI00191803.
PIRS43970.
UniGeneRn.4090

3D structure databases

HSSPHSSP built from PDB template 1JNK based on UniProtKB P53779.
SMRP49185. Positions 8-362.
ModBaseSearch...

Protein-protein interaction databases

STRINGP49185.

PTM databases

PhosphoSiteP49185.

Genome annotation databases

EnsemblENSRNOT00000027338; ENSRNOP00000027338; ENSRNOG00000020155; Rattus norvegicus. [Genome view]

Organism-specific databases

RGD621506. Mapk8.

Phylogenomic databases

HOVERGENP49185.

Enzyme and pathway databases

BRENDA2.7.11.24. 248.

Gene expression databases

ArrayExpressP49185.
GenevestigatorP49185.
GermOnlineENSRNOG00000020155. Rattus norvegicus.

Family and domain databases

InterProIPR008351. JNK_MAPK.
IPR003527. MAP_kinase_CS.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01772. JNKMAPKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameMK08_RAT
AccessionPrimary (citable) accession number: P49185
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: October 13, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents