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P49186 (MK09_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 9

Short name=MAP kinase 9
Short name=MAPK 9
EC=2.7.11.24
Alternative name(s):
SAPK-alpha
Stress-activated protein kinase JNK2
c-Jun N-terminal kinase 2
p54-alpha
Gene names
Name:Mapk9
Synonyms:Jnk2, Prkm9
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length423 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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

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 By similarity.

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 NFATC4 and DCLK2. Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 and GSK3B By similarity. Interacts with MECOM. Ref.2

Subcellular location

Cytoplasm By similarity. Nucleus 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 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro By similarity.

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
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from direct assay PubMed 10051439. Source: RGD

JUN phosphorylation

Inferred from mutant phenotype PubMed 16942465. Source: RGD

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 14522843. Source: GOC

cellular response to UV

Inferred from mutant phenotype PubMed 8875991. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern PubMed 17568197. Source: RGD

cellular response to interleukin-1

Inferred from expression pattern PubMed 10593906. Source: RGD

cellular response to lipopolysaccharide

Inferred from expression pattern PubMed 9475517. Source: RGD

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 9475517. Source: RGD

central nervous system development

Inferred from expression pattern PubMed 9748503. Source: RGD

neuron projection development

Inferred from mutant phenotype PubMed 16006144. Source: RGD

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 12029621PubMed 15504737. Source: RGD

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell morphogenesis involved in differentiation

Inferred from mutant phenotype PubMed 16006144. Source: RGD

positive regulation of chemokine production

Inferred from mutant phenotype PubMed 16942465. Source: RGD

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 14522843. Source: RGD

positive regulation of macrophage derived foam cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 10593906. Source: RGD

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from mutant phenotype PubMed 10593906. Source: RGD

positive regulation of prostaglandin biosynthetic process

Inferred from mutant phenotype PubMed 9786861. Source: RGD

positive regulation of prostaglandin secretion

Inferred from mutant phenotype PubMed 9786861. Source: RGD

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 16942465. Source: RGD

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 15504737. Source: RGD

protein phosphorylation

Inferred from direct assay PubMed 10051439. Source: RGD

protein targeting to mitochondrion

Inferred from expression pattern PubMed 15504737. Source: RGD

regulation of JNK cascade

Inferred from mutant phenotype PubMed 17348686. Source: RGD

regulation of protein ubiquitination

Inferred from mutant phenotype PubMed 8875991. Source: RGD

release of cytochrome c from mitochondria

Inferred from mutant phenotype PubMed 15504737. Source: RGD

response to amine

Inferred from expression pattern PubMed 18081878. Source: RGD

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from mutant phenotype PubMed 14522843. Source: RGD

response to mechanical stimulus

Inferred from expression pattern PubMed 16041628. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 18081878. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 15504737. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15504737. Source: RGD

cytosol

Inferred from direct assay PubMed 18385140. Source: MGI

mitochondrion

Inferred from direct assay PubMed 15504737. Source: RGD

nucleus

Inferred from direct assay PubMed 15504737. Source: RGD

   Molecular_functionATP binding

Inferred from direct assay PubMed 10051439. Source: RGD

JUN kinase activity

Inferred from direct assay PubMed 10051439PubMed 17064355. Source: RGD

cysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from mutant phenotype PubMed 14522843. Source: RGD

mitogen-activated protein kinase kinase kinase binding

Inferred from physical interaction PubMed 16006144. Source: RGD

transcription factor binding

Inferred from direct assay PubMed 9475517. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-2 (identifier: P49186-1)

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 Alpha-1 (identifier: P49186-2)

The sequence of this isoform differs from the canonical sequence as follows:
     216-230: GELVKGCVIFQGTDH → AEMVLHKSCSPGRDY

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 423423Mitogen-activated protein kinase 9
PRO_0000186275

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; by MAP2K7 By similarity
Modified residue1851Phosphotyrosine; by MAP2K4 By similarity

Natural variations

Alternative sequence216 – 23015GELVK…QGTDH → AEMVLHKSCSPGRDY in isoform Alpha-1.
VSP_004838

Sequences

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

Last modified February 1, 1996. Version 1.
Checksum: EE549B9F4F12F421

FASTA42348,017
        10         20         30         40         50         60 
MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP 

        70         80         90        100        110        120 
FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH 

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

       190        200        210        220        230        240 
MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ 

       250        260        270        280        290        300 
LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK 

       310        320        330        340        350        360 
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV 

       370        380        390        400        410        420 
MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST EHTLASDTDS SLDASTGPLE 


GCR 

« Hide

Isoform Alpha-1 [UniParc].

Checksum: 6419E1052BDC0292
Show »

FASTA42348,107

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2), PARTIAL PROTEIN SEQUENCE.
Tissue: Brain.
[2]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27112 mRNA. Translation: AAA42109.1.
L27111 mRNA. Translation: AAA42108.1.
PIRS43968.
RefSeqNP_001257473.1. NM_001270544.1.
NP_059018.1. NM_017322.2.
XP_006246379.1. XM_006246317.1.
UniGeneRn.177202.
Rn.9910.

3D structure databases

ProteinModelPortalP49186.
SMRP49186. Positions 7-363.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248408. 1 interaction.
IntActP49186. 2 interactions.
MINTMINT-5027617.
STRING10116.ENSRNOP00000003987.

PTM databases

PhosphoSiteP49186.

Proteomic databases

PaxDbP49186.
PRIDEP49186.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000003987; ENSRNOP00000003987; ENSRNOG00000002823. [P49186-1]
GeneID50658.
KEGGrno:50658.
UCSCRGD:628847. rat. [P49186-1]

Organism-specific databases

CTD5601.
RGD628847. Mapk9.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074271.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidP49186.
KOK04440.
OMAWEERNKN.
OrthoDBEOG7PCJGV.
PhylomeDBP49186.

Enzyme and pathway databases

BRENDA2.7.11.24. 5301.

Gene expression databases

ArrayExpressP49186.
GenevestigatorP49186.

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

NextBio610470.
PROP49186.

Entry information

Entry nameMK09_RAT
AccessionPrimary (citable) accession number: P49186
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families