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Protein

Mitogen-activated protein kinase kinase kinase 8

Gene

Map3k8

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

Functioni

Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei167ATPPROSITE-ProRule annotation1
Active sitei253Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi144 – 152ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 8 (EC:2.7.11.25)
Alternative name(s):
Tumor progression locus 2
Short name:
TPL-2
Gene namesi
Name:Map3k8
Synonyms:Tpl2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620969 Map3k8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862571 – 467Mitogen-activated protein kinase kinase kinase 8Add BLAST467

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineBy similarity1
Modified residuei80PhosphothreonineBy similarity1
Modified residuei138PhosphoserineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei290PhosphothreonineBy similarity1
Modified residuei400PhosphoserineBy similarity1
Modified residuei443PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63562
PRIDEiQ63562

PTM databases

iPTMnetiQ63562
PhosphoSitePlusiQ63562

Expressioni

Tissue specificityi

Expressed in spleen, thymus, liver and lung.1 Publication

Interactioni

Subunit structurei

Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation.1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022190

Structurei

3D structure databases

ProteinModelPortaliQ63562
SMRiQ63562
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini146 – 388Protein kinasePROSITE-ProRule annotationAdd BLAST243

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0201 Eukaryota
ENOG410XP9G LUCA
HOGENOMiHOG000285978
HOVERGENiHBG006306
InParanoidiQ63562
KOiK04415
PhylomeDBiQ63562

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017424 MAPKKK8
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038171 MAPKKK8, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q63562-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEYMSTGSDE KEEIDLLINH LNVSEVLDIM ENLYASEEPA VYEPSLMTMC
60 70 80 90 100
PDSNQNKEHS ESLLRSGQEV PWLSSVRYGT VEDLLAFANH ISNTTKHFYR
110 120 130 140 150
CRPQESGILL NMVISPQNGR YQIDSDVLLV PWKLTYRSIG SGFVPRGAFG
160 170 180 190 200
KVYLAQDMKT KKRMACKLIP VDQFKPSDVE IQACFRHENI AELYGAVLWG
210 220 230 240 250
DTVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG LDFLHSKKVI
260 270 280 290 300
HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYLPKDLRGT EIYMSPEVIL
310 320 330 340 350
CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL
360 370 380 390 400
EDIAGDCSPG MRELIEAALE RNPNHRPKAA DLLKHEALNP PREDQPRCQS
410 420 430 440 450
LDSALFDRKR LLSRKELELP ENIADSSCTG STEESEVLRR QRSLYIDLGA
460
LAGYFNIVRG PPTLEYG
Length:467
Mass (Da):52,807
Last modified:November 1, 1996 - v1
Checksum:i454E0E32768A4ABD
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V840G3V840_RAT
Mitogen-activated protein kinase ki...
Map3k8
565Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94454 mRNA Translation: AAA42185.1
PIRiA47388
RefSeqiNP_446299.1, NM_053847.1
UniGeneiRn.9939

Genome annotation databases

GeneIDi116596
KEGGirno:116596
UCSCiRGD:620969 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94454 mRNA Translation: AAA42185.1
PIRiA47388
RefSeqiNP_446299.1, NM_053847.1
UniGeneiRn.9939

3D structure databases

ProteinModelPortaliQ63562
SMRiQ63562
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022190

PTM databases

iPTMnetiQ63562
PhosphoSitePlusiQ63562

Proteomic databases

PaxDbiQ63562
PRIDEiQ63562

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi116596
KEGGirno:116596
UCSCiRGD:620969 rat

Organism-specific databases

CTDi1326
RGDi620969 Map3k8

Phylogenomic databases

eggNOGiKOG0201 Eukaryota
ENOG410XP9G LUCA
HOGENOMiHOG000285978
HOVERGENiHBG006306
InParanoidiQ63562
KOiK04415
PhylomeDBiQ63562

Miscellaneous databases

PROiPR:Q63562

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017424 MAPKKK8
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038171 MAPKKK8, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiM3K8_RAT
AccessioniPrimary (citable) accession number: Q63562
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 1, 1996
Last modified: November 22, 2017
This is version 126 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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