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Q91Y86

- MK08_MOUSE

UniProt

Q91Y86 - MK08_MOUSE

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Protein

Mitogen-activated protein kinase 8

Gene

Mapk8

Organism
Mus musculus (Mouse)
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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.By similarity5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.1 Publication

Enzyme regulationi

Inhibited by SERPINB3 (By similarity). 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 similarity1 Publication

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: UniProtKB-KW
  2. histone deacetylase regulator activity Source: Ensembl
  3. JUN kinase activity Source: UniProtKB
  4. kinase activity Source: MGI

GO - Biological processi

  1. cellular response to hydrogen peroxide Source: MGI
  2. cellular response to lipopolysaccharide Source: MGI
  3. cellular response to mechanical stimulus Source: Ensembl
  4. cellular response to nitric oxide Source: MGI
  5. determination of dorsal identity Source: MGI
  6. JNK cascade Source: UniProtKB
  7. JUN phosphorylation Source: MGI
  8. negative regulation of apoptotic process Source: Ensembl
  9. negative regulation of protein binding Source: Ensembl
  10. ossification Source: MGI
  11. peptidyl-serine phosphorylation Source: Ensembl
  12. peptidyl-threonine phosphorylation Source: MGI
  13. positive regulation of apoptotic signaling pathway Source: MGI
  14. positive regulation of deacetylase activity Source: Ensembl
  15. positive regulation of determination of dorsal identity Source: MGI
  16. positive regulation of gene expression Source: Ensembl
  17. programmed necrotic cell death Source: MGI
  18. protein phosphorylation Source: MGI
  19. regulation of gene expression Source: MGI
  20. regulation of protein localization Source: Ensembl
  21. response to cadmium ion Source: MGI
  22. response to UV Source: Ensembl
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. 3474.
ReactomeiREACT_188530. FCERI mediated MAPK activation.
REACT_188970. Oxidative Stress Induced Senescence.
REACT_202271. NRIF signals cell death from the nucleus.
REACT_204811. Activation of the AP-1 family of transcription factors.
REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_209641. NRAGE signals death through JNK.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 8 (EC:2.7.11.24)
Short name:
MAP kinase 8
Short name:
MAPK 8
Alternative name(s):
Stress-activated protein kinase JNK1
c-Jun N-terminal kinase 1
Gene namesi
Name:Mapk8
Synonyms:Jnk1, Prkm8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 14

Organism-specific databases

MGIiMGI:1346861. Mapk8.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytosol Source: MGI
  3. mitochondrion Source: MGI
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

At 14.5 dpc, brain intermediate zone and cortical plate are significantly thicker in mutant mice compared to wild type. The number of neuronal cells is increased in the cortical plate and intermediate zone. Cell cycle exit is decreased by 13% in the ventricular and subventricular zones. In 17.5 dpc brains, the ventricular zone was thinner in mutant mice compared to wild type animals, consistent with the increased number of neurons in the cortical plate. TUBB3 is consistently more diffuse and less structured in mutant telencephalon than in wild type.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 384384Mitogen-activated protein kinase 8PRO_0000186263Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei116 – 1161S-nitrosocysteineBy similarity
Modified residuei183 – 1831Phosphothreonine; by MAP2K71 Publication
Modified residuei185 – 1851Phosphotyrosine; by MAP2K41 Publication
Modified residuei377 – 3771Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated by TAOK2 (By similarity). Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme.By similarity2 Publications

Keywords - PTMi

Phosphoprotein, S-nitrosylation

Proteomic databases

MaxQBiQ91Y86.
PaxDbiQ91Y86.
PRIDEiQ91Y86.

PTM databases

PhosphoSiteiQ91Y86.

Expressioni

Developmental stagei

At 15.5 dpc, mid to low expression throughout the midbrain, with more prominent levels in the telencephalon, especially in the intermediate zone, the midbrain roof, the olfactory epithelium, the inferior colliculus, and the medulla oblongata. telencephalon revealed concentrated (at protein level).1 Publication

Inductioni

In T-cells, following T-cell receptor (TCR) activation. Levels peak 48 hours after TCR and CD-28 costimulation.1 Publication

Gene expression databases

BgeeiQ91Y86.
CleanExiMM_MAPK8.
ExpressionAtlasiQ91Y86. baseline and differential.
GenevestigatoriQ91Y86.

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. Forms a complex with MAPK8IP1 and ARHGEF28. Interacts with TP53 and WWOX. Interacts with JAMP. Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates (By similarity). Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
JunP056272EBI-298784,EBI-764369

Protein-protein interaction databases

BioGridi204971. 16 interactions.
IntActiQ91Y86. 7 interactions.
MINTiMINT-1204569.
STRINGi10090.ENSMUSP00000022504.

Structurei

3D structure databases

ProteinModelPortaliQ91Y86.
SMRiQ91Y86. Positions 7-364.
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.
InParanoidiQ91Y86.
KOiK04440.
OrthoDBiEOG7PCJGV.
PhylomeDBiQ91Y86.
TreeFamiTF105100.

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]

Sequencei

Sequence statusi: Complete.

Q91Y86-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER
60 70 80 90 100
NVAIKKLSRP FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE
110 120 130 140 150
FQDVYIVMEL MDANLCQVIQ MELDHERMSY LLYQMLCGIK HLHSAGIIHR
160 170 180 190 200
DLKPSNIVVK SDCTLKILDF GLARTAGTSF MMTPYVVTRY YRAPEVILGM
210 220 230 240 250
GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ LGTPCPEFMK
260 270 280 290 300
KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK
310 320 330 340 350
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE
360 370 380
EWKELIYKEV MDLEERTKNG VIRGQPSPLA QVQQ
Length:384
Mass (Da):44,229
Last modified:December 1, 2001 - v1
Checksum:iA7320EF933E9CF85
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB005663 mRNA. Translation: BAA85875.1.
CCDSiCCDS36869.1.
RefSeqiNP_057909.1. NM_016700.4.
UniGeneiMm.21495.

Genome annotation databases

EnsembliENSMUST00000111945; ENSMUSP00000107576; ENSMUSG00000021936.
GeneIDi26419.
KEGGimmu:26419.
UCSCiuc007szt.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB005663 mRNA. Translation: BAA85875.1 .
CCDSi CCDS36869.1.
RefSeqi NP_057909.1. NM_016700.4.
UniGenei Mm.21495.

3D structure databases

ProteinModelPortali Q91Y86.
SMRi Q91Y86. Positions 7-364.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204971. 16 interactions.
IntActi Q91Y86. 7 interactions.
MINTi MINT-1204569.
STRINGi 10090.ENSMUSP00000022504.

Chemistry

BindingDBi Q91Y86.
ChEMBLi CHEMBL1795174.

PTM databases

PhosphoSitei Q91Y86.

Proteomic databases

MaxQBi Q91Y86.
PaxDbi Q91Y86.
PRIDEi Q91Y86.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000111945 ; ENSMUSP00000107576 ; ENSMUSG00000021936 .
GeneIDi 26419.
KEGGi mmu:26419.
UCSCi uc007szt.3. mouse.

Organism-specific databases

CTDi 5599.
MGIi MGI:1346861. Mapk8.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074271.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi Q91Y86.
KOi K04440.
OrthoDBi EOG7PCJGV.
PhylomeDBi Q91Y86.
TreeFami TF105100.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 3474.
Reactomei REACT_188530. FCERI mediated MAPK activation.
REACT_188970. Oxidative Stress Induced Senescence.
REACT_202271. NRIF signals cell death from the nucleus.
REACT_204811. Activation of the AP-1 family of transcription factors.
REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_209641. NRAGE signals death through JNK.

Miscellaneous databases

NextBioi 304433.
PROi Q91Y86.
SOURCEi Search...

Gene expression databases

Bgeei Q91Y86.
CleanExi MM_MAPK8.
ExpressionAtlasi Q91Y86. baseline and differential.
Genevestigatori Q91Y86.

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

« Hide 'large scale' publications
  1. "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway."
    Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K., Hibi M., Nakabeppu Y., Shiba T., Yamamoto K.
    Mol. Cell. Biol. 19:7539-7548(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAPK8IP3.
    Tissue: Brain.
  2. "JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases."
    Hu M.C., Qiu W.R., Wang Y.P.
    Oncogene 15:2277-2287(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF TP53.
  3. "Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity."
    Yang D., Tournier C., Wysk M., Lu H.-T., Xu J., Davis R.J., Flavell R.A.
    Proc. Natl. Acad. Sci. U.S.A. 94:3004-3009(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY MAP2K4.
    Tissue: Embryonic stem cell.
  4. "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase."
    Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.
    Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY MAP2K7, COFACTOR.
  5. "JNK is required for effector T-cell function but not for T-cell activation."
    Dong C., Yang D.D., Tournier C., Whitmarsh A.J., Xu J., Davis R.J., Flavell R.A.
    Nature 405:91-94(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, INDUCTION.
    Tissue: Embryonic stem cell and T-cell.
  6. "The AP-1 repressor, JDP2, is a bona fide substrate for the c-Jun N-terminal kinase."
    Katz S., Heinrich R., Aronheim A.
    FEBS Lett. 506:196-200(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF JDP2.
  7. Cited for: SUBUNIT, PHOSPHORYLATION AT THR-183 AND TYR-185.
    Tissue: Hippocampus.
  8. "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors."
    Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.
    Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SPAG9.
  9. "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] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND ARHGEF28.
  10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic brain.
  11. "JAMP, a Jun N-terminal kinase 1 (JNK1)-associated membrane protein, regulates duration of JNK activity."
    Kadoya T., Khurana A., Tcherpakov M., Bromberg K.D., Didier C., Broday L., Asahara T., Bhoumik A., Ronai Z.
    Mol. Cell. Biol. 25:8619-8630(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JAMP.
  12. "JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length."
    Tararuk T., Ostman N., Li W., Bjorkblom B., Padzik A., Zdrojewska J., Hongisto V., Herdegen T., Konopka W., Courtney M.J., Coffey E.T.
    J. Cell Biol. 173:265-277(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  13. "JNK-mediated turnover and stabilization of the transcription factor p45/NF-E2 during differentiation of murine erythroleukemia cells."
    Lee T.L., Shyu Y.C., Hsu P.H., Chang C.W., Wen S.C., Hsiao W.Y., Tsai M.D., Shen C.K.
    Proc. Natl. Acad. Sci. U.S.A. 107:52-57(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NFE2, FUNCTION.
  14. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiMK08_MOUSE
AccessioniPrimary (citable) accession number: Q91Y86
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2002
Last sequence update: December 1, 2001
Last modified: October 29, 2014
This is version 142 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, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3