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P49185

- MK08_RAT

UniProt

P49185 - MK08_RAT

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Protein

Mitogen-activated protein kinase 8

Gene

Mapk8

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 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 similarity.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.1 Publication

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. Inhibited by SERPINB3 By similarity. Inhibited by IFN-gamma-induced S-nitrosylation.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: UniProtKB-KW
  2. JUN kinase activity Source: UniProtKB

GO - Biological processi

  1. inflammatory response Source: RGD
  2. JNK cascade Source: UniProtKB
  3. JUN phosphorylation Source: GOC
  4. negative regulation of apoptotic process Source: RGD
  5. neuron projection development Source: RGD
  6. positive regulation of apoptotic process Source: RGD
  7. positive regulation of cell migration Source: RGD
  8. positive regulation of DNA replication Source: RGD
  9. positive regulation of microtubule polymerization Source: RGD
  10. regulation of transcription, DNA-templated Source: RGD
  11. response to heat Source: RGD
  12. response to hydrogen peroxide Source: RGD
  13. response to osmotic stress Source: RGD
  14. response to steroid hormone Source: RGD
  15. signal transduction 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.

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):
SAPK gamma
Stress-activated protein kinase JNK1
c-Jun N-terminal kinase 1
p54 gamma
Gene namesi
Name:Mapk8
Synonyms:Jnk1, Prkm8
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621506. Mapk8.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus By similarity
Note: In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction.

GO - Cellular componenti

  1. axon Source: RGD
  2. cytoplasm Source: RGD
  3. cytosol Source: Reactome
  4. dendrite cytoplasm Source: RGD
  5. mitochondrion Source: RGD
  6. nucleus Source: RGD
  7. perikaryon Source: RGD
  8. vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi116 – 1161C → S: Abolished inhibitory effect of IFN-gamma on JNK1 activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 411411Mitogen-activated protein kinase 8PRO_0000186264Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei116 – 1161S-nitrosocysteine; in inhibited form1 Publication
Modified residuei183 – 1831Phosphothreonine; by MAP2K7By similarity
Modified residuei185 – 1851Phosphotyrosine; by MAP2K4By similarity
Modified residuei377 – 3771PhosphoserineBy similarity

Post-translational modificationi

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2 By similarity.By similarity
Nitrosylated upon IFN-gamma-induced endogenous NO production, which inhibits the enzyme.1 Publication

Keywords - PTMi

Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiP49185.
PRIDEiP49185.

PTM databases

PhosphoSiteiP49185.

Expressioni

Gene expression databases

GenevestigatoriP49185.

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 TP53, WWOX and JAMP. Interacts with NFATC4. Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells. 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. Forms a complex with MAPK8IP1 and ARHGEF28. Interacts with STMN2, STMN3 and STMN4.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gria2P19491-32EBI-7456505,EBI-9118256
Gria4P194932EBI-7456505,EBI-7761834
JunP173252EBI-7456505,EBI-7709365
Syt4P502325EBI-7456505,EBI-540118

Protein-protein interaction databases

IntActiP49185. 6 interactions.
MINTiMINT-1500743.
STRINGi10116.ENSRNOP00000027338.

Structurei

3D structure databases

ProteinModelPortaliP49185.
SMRiP49185. 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.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49185.
KOiK04440.
PhylomeDBiP49185.

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.

P49185-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRSKRDNNF YSVEIADSTF 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 LKILFPGRDY IDQWNKVIEQ LGTPCPEFMK
260 270 280 290 300
KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK
310 320 330 340 350
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE
360 370 380 390 400
EWKELIYKEV MDLEERTKNG VIRGQPSPLG AAVINGSQHP VSSPSVNDMS
410
SMSTDPTLAS D
Length:411
Mass (Da):46,807
Last modified:February 1, 1996 - v1
Checksum:i04E388B4F94633D4
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L27129 mRNA. Translation: AAA42111.1.
PIRiS43970.
RefSeqiNP_446281.1. NM_053829.1.
UniGeneiRn.4090.

Genome annotation databases

GeneIDi116554.
KEGGirno:116554.
UCSCiRGD:621506. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L27129 mRNA. Translation: AAA42111.1 .
PIRi S43970.
RefSeqi NP_446281.1. NM_053829.1.
UniGenei Rn.4090.

3D structure databases

ProteinModelPortali P49185.
SMRi P49185. Positions 7-364.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P49185. 6 interactions.
MINTi MINT-1500743.
STRINGi 10116.ENSRNOP00000027338.

Chemistry

ChEMBLi CHEMBL5718.

PTM databases

PhosphoSitei P49185.

Proteomic databases

PaxDbi P49185.
PRIDEi P49185.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 116554.
KEGGi rno:116554.
UCSCi RGD:621506. rat.

Organism-specific databases

CTDi 5599.
RGDi 621506. Mapk8.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi P49185.
KOi K04440.
PhylomeDBi P49185.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 5301.

Gene expression databases

Genevestigatori P49185.

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].
    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND ARHGEF28.
  5. "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: FUNCTION, INTERACTION WITH MAPK8IP1; STMN2; STMN3 AND STMN4, SUBCELLULAR LOCATION.
  6. Cited for: FUNCTION.

Entry informationi

Entry nameiMK08_RAT
AccessioniPrimary (citable) accession number: P49185
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: October 29, 2014
This is version 140 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3