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P49186

- MK09_RAT

UniProt

P49186 - MK09_RAT

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Protein

Mitogen-activated protein kinase 9

Gene

Mapk9

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.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

  1. ATP binding Source: RGD
  2. cysteine-type endopeptidase activator activity involved in apoptotic process Source: RGD
  3. JUN kinase activity Source: RGD
  4. mitogen-activated protein kinase kinase kinase binding Source: RGD
  5. transcription factor binding Source: RGD

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GOC
  2. cellular response to growth factor stimulus Source: RGD
  3. cellular response to interleukin-1 Source: RGD
  4. cellular response to lipopolysaccharide Source: RGD
  5. cellular response to tumor necrosis factor Source: RGD
  6. cellular response to UV Source: RGD
  7. central nervous system development Source: RGD
  8. JNK cascade Source: RGD
  9. JUN phosphorylation Source: RGD
  10. neuron projection development Source: RGD
  11. positive regulation of apoptotic process Source: RGD
  12. positive regulation of apoptotic signaling pathway Source: Ensembl
  13. positive regulation of cell morphogenesis involved in differentiation Source: RGD
  14. positive regulation of chemokine production Source: RGD
  15. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
  16. positive regulation of macrophage derived foam cell differentiation Source: Ensembl
  17. positive regulation of nitric oxide biosynthetic process Source: RGD
  18. positive regulation of nitric-oxide synthase biosynthetic process Source: RGD
  19. positive regulation of prostaglandin biosynthetic process Source: RGD
  20. positive regulation of prostaglandin secretion Source: RGD
  21. positive regulation of protein phosphorylation Source: RGD
  22. positive regulation of transcription, DNA-templated Source: RGD
  23. protein phosphorylation Source: RGD
  24. protein targeting to mitochondrion Source: RGD
  25. regulation of JNK cascade Source: RGD
  26. regulation of protein ubiquitination Source: RGD
  27. release of cytochrome c from mitochondria Source: RGD
  28. response to amine Source: RGD
  29. response to cadmium ion Source: Ensembl
  30. response to drug Source: RGD
  31. response to mechanical stimulus Source: RGD
  32. response to organic substance Source: RGD
  33. response to toxic substance Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 5301.
ReactomeiREACT_195202. FCERI mediated MAPK activation.
REACT_203770. Oxidative Stress Induced Senescence.

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: Chromosome 10

Organism-specific databases

RGDi628847. Mapk9.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. cytosol Source: MGI
  3. mitochondrion Source: RGD
  4. 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.
GenevestigatoriP49186.

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.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49186.
KOiK04440.
OMAiSSMSTEH.
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. Align

Isoform Alpha-2 (identifier: P49186) [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:
EMBL
GenBank
DDBJ
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

EnsembliENSRNOT00000003987; ENSRNOP00000003987; ENSRNOG00000002823. [P49186-1]
GeneIDi50658.
KEGGirno:50658.
UCSCiRGD:628847. rat. [P49186-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L27112 mRNA. Translation: AAA42109.1 .
L27111 mRNA. Translation: AAA42108.1 .
PIRi S43968.
RefSeqi NP_001257473.1. NM_001270544.1.
NP_059018.1. NM_017322.2. [P49186-1 ]
XP_006246379.1. XM_006246317.1. [P49186-1 ]
UniGenei Rn.177202.
Rn.9910.

3D structure databases

ProteinModelPortali P49186.
SMRi P49186. Positions 7-363.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248408. 1 interaction.
IntActi P49186. 2 interactions.
MINTi MINT-5027617.
STRINGi 10116.ENSRNOP00000003987.

PTM databases

PhosphoSitei P49186.

Proteomic databases

PaxDbi P49186.
PRIDEi P49186.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000003987 ; ENSRNOP00000003987 ; ENSRNOG00000002823 . [P49186-1 ]
GeneIDi 50658.
KEGGi rno:50658.
UCSCi RGD:628847. rat. [P49186-1 ]

Organism-specific databases

CTDi 5601.
RGDi 628847. Mapk9.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074271.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi P49186.
KOi K04440.
OMAi SSMSTEH.
OrthoDBi EOG7PCJGV.
PhylomeDBi P49186.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 5301.
Reactomei REACT_195202. FCERI mediated MAPK activation.
REACT_203770. Oxidative Stress Induced Senescence.

Miscellaneous databases

NextBioi 610470.
PROi P49186.

Gene expression databases

ExpressionAtlasi P49186. baseline and differential.
Genevestigatori P49186.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01772. JNKMAPKINASE.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 136 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