Reviewed, UniProtKB/Swiss-Prot Q07174 (M3K8_MOUSE)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase 8
    EC=2.7.11.25
Alternative name(s):
    COT proto-oncogene serine/threonine-protein kinase
    Cancer Osaka thyroid oncogene
      Short name=C-COT

Gene names

Name:	Map3k8
Synonyms:	Cot

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for TLR4 activation of the MEK/ERK pathway. Able to activate NF-kappa-B 1 by stimulating proteasome-mediated proteolysis of NF-kappa-B 1/p105. Plays a role in the cell cycle By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Subunit structure	Forms a ternary complex with NFKB1 and TNIP2 By similarity.
Subcellular location	Cytoplasm.
Tissue specificity	High in adult submandibular gland, thymus, spleen and newborn digestive tract.
Post-translational modification	Autophosphorylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Disease	Proto-oncogene
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RIPK1	Q13546	1	EBI-309771,EBI-358507	From a different organism.
Ripk1	Q60855	1	EBI-309771,EBI-529119

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 467	467	Mitogen-activated protein kinase kinase kinase 8		PRO_0000086256
Regions
	Domain	138 – 388	251	Protein kinase
	Nucleotide binding	144 – 152	9	ATP By similarity
Sites
	Active site	253	1	Proton acceptor By similarity
	Binding site	167	1	ATP By similarity
Amino acid modifications
	Modified residue	141	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q07174-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 60C2A34E530866BE	FASTA	467	52,942
	10 20 30 40 50 60 MEYMSTGSDE KEEIDLLIKH LNVSEVIDIM ENLYASEEPG VYEPSLMTMY PDSNQNEERS 70 80 90 100 110 120 ESLLRSGQEV PWLSSVRYGT VEDLLAFANH VSNMTKHFYG RRPQECGILL NMVISPQNGR 130 140 150 160 170 180 YQIDSDVLLV PWKLTYRNIG SGFVPRGAFG KVYLAQDMKT KKRMACKLIP IDQFKPSDVE 190 200 210 220 230 240 IQACFRHENI AELYGAVLWG DTVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHILKG 250 260 270 280 290 300 LDFLHSKKVI HHDIKPSNIV FMSTKAVLVD FGLSVKMTED VYLPKDLRGT EIYMSPEVIL 310 320 330 340 350 360 CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL EDIAGDCSPG 370 380 390 400 410 420 MRELIEAALE RNPNHRPKAA DLLKHEALNP PREDQPRCQS LDSALFERKR LLSRKELQLP 430 440 450 460 ENIADSSCTG STEESEVLRR QRSLYIDLGA LAGYFNIVRG PPTLEYG

References

[1]	"The murine cot proto-oncogene: genome structure and tissue-specific expression." Ohara R., Miyoshi J., Aoki M., Toyoshima K. Jpn. J. Cancer Res. 84:518-525(1993) [PubMed: 8320169] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 X CBA. Tissue: Thymus.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D13759 mRNA. Translation: BAA02905.1.
IPI	IPI00308992.
PIR	I49609.
RefSeq	NP_031772.1.
UniGene	Mm.3275
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q07174. 5 interactions.
STRING	Q07174.
PTM databases
PhosphoSite	Q07174.
Proteomic databases
PRIDE	Q07174.
Genome annotation databases
Ensembl	ENSMUST00000025078; ENSMUSP00000025078; ENSMUSG00000024235; Mus musculus. [Genome view]
GeneID	26410.
KEGG	mmu:26410.
UCSC	uc008dye.1. mouse.
Organism-specific databases
CTD	26410.
MGI	MGI:1346878. Map3k8.
Phylogenomic databases
eggNOG	roNOG09026.
HOGENOM	HBG717754.
HOVERGEN	Q07174.
InParanoid	Q07174.
OMA	DCSPGMR.
OrthoDB	EOG95B41S.
PhylomeDB	Q07174.
Enzyme and pathway databases
BRENDA	2.7.11.25. 244.
Gene expression databases
ArrayExpress	Q07174.
Bgee	Q07174.
CleanEx	MM_MAP3K8.
Genevestigator	Q07174.
GermOnline	ENSMUSG00000024235. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR017424. MAPKKK8. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038171. MAPKKK8. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	304397.
SOURCE	Search...

Entry information

Entry name

M3K8_MOUSE

Accession

Primary (citable) accession number: Q07174

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	January 19, 2010
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)