Map3k8

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 key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	167	ATPPROSITE-ProRule annotation		1
Active siteⁱ	253	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	144 – 152	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
magnesium ion binding Source: InterPro
MAP kinase kinase kinase activity
Source: Reactome
Inferred from experimentⁱ
- 8631303
protein serine/threonine kinase activity Source: GO_Central

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of protein kinase activity Source: GO_Central
cell cycle Source: UniProtKB-KW
immune system process Source: UniProtKB-KW
regulation of apoptotic process Source: GO_Central
regulation of mitotic cell cycle Source: GO_Central
signal transduction by protein phosphorylation Source: GO_Central
stress-activated protein kinase signaling cascade Source: GO_Central

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Cell cycle, Immunity
Ligand	ATP-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
Organismⁱ	Rattus norvegicus (Rat)
Taxonomic identifierⁱ	10116 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesⁱ	UP000002494 Componentⁱ: Unplaced

Organism-specific databases

Rat genome database More...RGDⁱ	620969 Map3k8

RGDⁱ

620969 Map3k8

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

Proto-oncogene

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000086257	1 – 467	Mitogen-activated protein kinase kinase kinase 8Add BLAST		467

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	62	PhosphoserineBy similarity	1
Modified residueⁱ	80	PhosphothreonineBy similarity	1
Modified residueⁱ	138	PhosphoserineCombined sources	1
Modified residueⁱ	141	PhosphoserineCombined sources	1
Modified residueⁱ	290	PhosphothreonineBy similarity	1
Modified residueⁱ	400	PhosphoserineBy similarity	1
Modified residueⁱ	443	PhosphoserineBy similarity	1

Post-translational modificationⁱ

Autophosphorylated.By similarity

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

PaxDbⁱ	Q63562
PRIDEⁱ	Q63562

PTM databases

iPTMnetⁱ	Q63562
PhosphoSitePlusⁱ	Q63562

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

STRINGⁱ	10116.ENSRNOP00000022190

STRINGⁱ

10116.ENSRNOP00000022190

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q63562
SMRⁱ	Q63562
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	146 – 388	Protein kinasePROSITE-ProRule annotationAdd BLAST		243

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated

Phylogenomic databases

eggNOGⁱ	KOG0201 Eukaryota ENOG410XP9G LUCA
HOGENOMⁱ	HOG000285978
HOVERGENⁱ	HBG006306
InParanoidⁱ	Q63562
KEGG Orthology (KO) More...KOⁱ	K04415
PhylomeDBⁱ	Q63562

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017424 MAPKKK8 IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF038171 MAPKKK8, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View 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 all Align All

Q63562-1 [UniParc]FASTA Add 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.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	G3V840	G3V840_RAT		Mitogen-activated protein kinase ki... Mitogen-activated protein kinase kinase kinase 8	Map3k8	565	Annotation score:

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M94454 mRNA Translation: AAA42185.1
PIRⁱ	A47388
NCBI Reference Sequences More...RefSeqⁱ	NP_446299.1, NM_053847.1
UniGeneⁱ	Rn.9939

Genome annotation databases

GeneIDⁱ	116596
KEGGⁱ	rno:116596
UCSC genome browser More...UCSCⁱ	RGD:620969 rat

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q63562	Mitogen-activated protein kinase kinase kinase 8	)	HUMAN		467	UniRef90_P41279
Mitogen-activated protein kinase kinase kinase 8		MOUSE		467
Uncharacterized protein		PAPAN		572
Uncharacterized protein		MACNE		572
Mitogen-activated protein kinase kinase kinase 8		OTOGA		469
+94

Protein	Similar proteins		Species	Score	Length	Source
Q63562	Mitogen-activated protein kinase kinase kinase 8	)	HUMAN		467	UniRef50_P41279
Mitogen-activated protein kinase kinase kinase 8		MOUSE		467
Uncharacterized protein		PAPAN		572
Uncharacterized protein		MACNE		572
Mitogen-activated protein kinase kinase kinase 8		OTOGA		469
+299

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M94454 mRNA Translation: AAA42185.1
PIRⁱ	A47388
RefSeqⁱ	NP_446299.1, NM_053847.1
UniGeneⁱ	Rn.9939

3D structure databases

ProteinModelPortalⁱ	Q63562
SMRⁱ	Q63562
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10116.ENSRNOP00000022190

STRINGⁱ

10116.ENSRNOP00000022190

PTM databases

iPTMnetⁱ	Q63562
PhosphoSitePlusⁱ	Q63562

Proteomic databases

PaxDbⁱ	Q63562
PRIDEⁱ	Q63562

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	116596
KEGGⁱ	rno:116596
UCSCⁱ	RGD:620969 rat

Organism-specific databases

CTDⁱ	1326
RGDⁱ	620969 Map3k8

Phylogenomic databases

eggNOGⁱ	KOG0201 Eukaryota ENOG410XP9G LUCA
HOGENOMⁱ	HOG000285978
HOVERGENⁱ	HBG006306
InParanoidⁱ	Q63562
KOⁱ	K04415
PhylomeDBⁱ	Q63562

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q63562

PROⁱ

PR:Q63562

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR017424 MAPKKK8 IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF038171 MAPKKK8, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	M3K8_RAT
Accessionⁱ	Q63562Primary (citable) accession number: Q63562
Entry historyⁱ	Integrated 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 statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

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UniParc

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UniProtKB - Q63562 (M3K8_RAT)

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Mitogen-activated protein kinase kinase kinase 8

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Cytosol

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ