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Protein

Mitogen-activated protein kinase 9

Gene

Mapk9

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei55 – 551ATPPROSITE-ProRule annotation
Active sitei151 – 1511Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi32 – 409ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: RGD
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: RGD
  • JUN kinase activity Source: RGD
  • mitogen-activated protein kinase kinase kinase binding Source: RGD
  • transcription factor binding Source: RGD

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GOC
  • cellular response to growth factor stimulus Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • cellular response to lipopolysaccharide Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • cellular response to UV Source: RGD
  • central nervous system development Source: RGD
  • JNK cascade Source: RGD
  • JUN phosphorylation Source: RGD
  • neuron projection development Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of cell morphogenesis involved in differentiation Source: RGD
  • positive regulation of chemokine production Source: RGD
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
  • positive regulation of nitric oxide biosynthetic process Source: RGD
  • positive regulation of nitric-oxide synthase biosynthetic process Source: RGD
  • positive regulation of prostaglandin biosynthetic process Source: RGD
  • positive regulation of prostaglandin secretion Source: RGD
  • positive regulation of protein phosphorylation Source: RGD
  • positive regulation of transcription, DNA-templated Source: RGD
  • protein phosphorylation Source: RGD
  • protein targeting to mitochondrion Source: RGD
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of JNK cascade Source: RGD
  • regulation of protein ubiquitination Source: RGD
  • release of cytochrome c from mitochondria Source: RGD
  • response to amine Source: RGD
  • response to drug Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to organic substance Source: RGD
  • response to toxic substance Source: RGD
  • rhythmic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 5301.
ReactomeiREACT_300308. Activation of the AP-1 family of transcription factors.
REACT_302239. Oxidative Stress Induced Senescence.
REACT_347894. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_353315. FCERI mediated MAPK activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 9 (EC:2.7.11.24)
Short name:
MAP kinase 9
Short name:
MAPK 9
Alternative name(s):
SAPK-alpha
Stress-activated protein kinase JNK2
c-Jun N-terminal kinase 2
p54-alpha
Gene namesi
Name:Mapk9
Synonyms:Jnk2, Prkm9
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi628847. Mapk9.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: MGI
  • mitochondrion Source: RGD
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 423423Mitogen-activated protein kinase 9PRO_0000186275Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei183 – 1831Phosphothreonine; by MAP2K7By similarity
Modified residuei185 – 1851Phosphotyrosine; by MAP2K4By similarity

Post-translational modificationi

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP49186.
PRIDEiP49186.

PTM databases

PhosphoSiteiP49186.

Expressioni

Gene expression databases

ExpressionAtlasiP49186. baseline and differential.
GenevisibleiP49186. RN.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

BioGridi248408. 1 interaction.
IntActiP49186. 2 interactions.
MINTiMINT-5027617.
STRINGi10116.ENSRNOP00000003987.

Structurei

3D structure databases

ProteinModelPortaliP49186.
SMRiP49186. Positions 7-363.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 321296Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi183 – 1853TXY

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49186.
KOiK04440.
OMAiPSLEFMN.
OrthoDBiEOG7PCJGV.
PhylomeDBiP49186.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01772. JNKMAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-2 (identifier: P49186-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI
60 70 80 90 100
NVAVKKLSRP FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE
110 120 130 140 150
FQDVYLVMEL MDANLCQVIH MELDHERMSY LLYQMLCGIK HLHSAGIIHR
160 170 180 190 200
DLKPSNIVVK SDCTLKILDF GLARTACTNF MMTPYVVTRY YRAPEVILGM
210 220 230 240 250
GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ LGTPSAEFMK
260 270 280 290 300
KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK
310 320 330 340 350
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE
360 370 380 390 400
EWKELIYKEV MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST
410 420
EHTLASDTDS SLDASTGPLE GCR
Length:423
Mass (Da):48,017
Last modified:February 1, 1996 - v1
Checksum:iEE549B9F4F12F421
GO
Isoform Alpha-1 (identifier: P49186-2) [UniParc]FASTAAdd to basket

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

Show »
Length:423
Mass (Da):48,107
Checksum:i6419E1052BDC0292
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei216 – 23015GELVK…QGTDH → AEMVLHKSCSPGRDY in isoform Alpha-1. 1 PublicationVSP_004838Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27112 mRNA. Translation: AAA42109.1.
L27111 mRNA. Translation: AAA42108.1.
PIRiS43968.
RefSeqiNP_001257473.1. NM_001270544.1.
NP_059018.1. NM_017322.2. [P49186-1]
XP_006246379.1. XM_006246317.1. [P49186-1]
UniGeneiRn.177202.
Rn.9910.

Genome annotation databases

GeneIDi50658.
KEGGirno:50658.
UCSCiRGD:628847. rat. [P49186-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27112 mRNA. Translation: AAA42109.1.
L27111 mRNA. Translation: AAA42108.1.
PIRiS43968.
RefSeqiNP_001257473.1. NM_001270544.1.
NP_059018.1. NM_017322.2. [P49186-1]
XP_006246379.1. XM_006246317.1. [P49186-1]
UniGeneiRn.177202.
Rn.9910.

3D structure databases

ProteinModelPortaliP49186.
SMRiP49186. Positions 7-363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248408. 1 interaction.
IntActiP49186. 2 interactions.
MINTiMINT-5027617.
STRINGi10116.ENSRNOP00000003987.

PTM databases

PhosphoSiteiP49186.

Proteomic databases

PaxDbiP49186.
PRIDEiP49186.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi50658.
KEGGirno:50658.
UCSCiRGD:628847. rat. [P49186-1]

Organism-specific databases

CTDi5601.
RGDi628847. Mapk9.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49186.
KOiK04440.
OMAiPSLEFMN.
OrthoDBiEOG7PCJGV.
PhylomeDBiP49186.

Enzyme and pathway databases

BRENDAi2.7.11.24. 5301.
ReactomeiREACT_300308. Activation of the AP-1 family of transcription factors.
REACT_302239. Oxidative Stress Induced Senescence.
REACT_347894. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_353315. FCERI mediated MAPK activation.

Miscellaneous databases

NextBioi610470.
PROiP49186.

Gene expression databases

ExpressionAtlasiP49186. baseline and differential.
GenevisibleiP49186. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01772. JNKMAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. 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.

Entry informationi

Entry nameiMK09_RAT
AccessioniPrimary (citable) accession number: P49186
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.