Reviewed, UniProtKB/Swiss-Prot Q63562 (M3K8_RAT)

Names and origin

Protein names

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 names

Name:	Map3k8
Synonyms:	Tpl2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Ref.2
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	Expressed in spleen, thymus, liver and lung.
Post-translational modification	Autophosphorylated.
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
Complete GO annotation...

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_0000086257
Regions
	Domain	146 – 388	243	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)
	Q63562-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 454E0E32768A4ABD	FASTA	467	52,807
	10 20 30 40 50 60 MEYMSTGSDE KEEIDLLINH LNVSEVLDIM ENLYASEEPA VYEPSLMTMC PDSNQNKEHS 70 80 90 100 110 120 ESLLRSGQEV PWLSSVRYGT VEDLLAFANH ISNTTKHFYR CRPQESGILL NMVISPQNGR 130 140 150 160 170 180 YQIDSDVLLV PWKLTYRSIG SGFVPRGAFG KVYLAQDMKT KKRMACKLIP VDQFKPSDVE 190 200 210 220 230 240 IQACFRHENI AELYGAVLWG DTVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG 250 260 270 280 290 300 LDFLHSKKVI HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYLPKDLRGT EIYMSPEVIL 310 320 330 340 350 360 CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL EDIAGDCSPG 370 380 390 400 410 420 MRELIEAALE RNPNHRPKAA DLLKHEALNP PREDQPRCQS LDSALFDRKR LLSRKELELP 430 440 450 460 ENIADSSCTG STEESEVLRR QRSLYIDLGA LAGYFNIVRG PPTLEYG

References

[1]	"Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation." Patriotis C., Makris A., Bear S.E., Tsichlis P.N. Proc. Natl. Acad. Sci. U.S.A. 90:2251-2255(1993) [PubMed: 7681591] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Long Evans. Tissue: Liver.
[2]	"TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105." Belich M.P., Salmeron A., Johnston L.H., Ley S.C. Nature 397:363-368(1999) [PubMed: 9950430] [Abstract] Cited for: FUNCTION, INTERACTION WITH NFKB1/P105.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M94454 mRNA. Translation: AAA42185.1.
IPI	IPI00210121.
PIR	A47388.
RefSeq	NP_446299.1.
UniGene	Rn.9939
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q63562.
PTM databases
PhosphoSite	Q63562.
Genome annotation databases
Ensembl	ENSRNOT00000022190; ENSRNOP00000022190; ENSRNOG00000016378; Rattus norvegicus. [Genome view]
GeneID	116596.
KEGG	rno:116596.
UCSC	NM_053847. rat.
Organism-specific databases
CTD	116596.
RGD	620969. Map3k8.
Phylogenomic databases
HOVERGEN	Q63562.
Enzyme and pathway databases
BRENDA	2.7.11.25. 248.
Gene expression databases
ArrayExpress	Q63562.
Genevestigator	Q63562.
GermOnline	ENSRNOG00000016378. Rattus norvegicus.
Family and domain databases
InterPro	IPR017424. MAPKKK8. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038171. MAPKKK8. 1 hit.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
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	619291.

Entry information

Entry name

M3K8_RAT

Accession

Primary (citable) accession number: Q63562

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	November 1, 1996
Last modified:	October 13, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)