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FLASH GENE

Symbol

MAP3K8

contributors: mct - updated : 16-01-2019

HGNC name	mitogen-activated protein kinase kinase kinase 8
HGNC id	6860

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10p11.23      Physical location : 30.722.865 - 30.750.761
Synonym name	Ewing sarcoma transformant
	cancer osaka thyroid oncogene
	COT (cancer osaka thyroid) oncogene
	proto-oncogene serine/threonine-protein kinase
	tumor progression locus 2
Synonym symbol(s)	COT, TPL2, EST, ESTF, MEKK8, Tpl-2, c-COT, FLJ10486
EC.number	2.7.11.25

DNA

TYPE	functioning gene
STRUCTURE	27.90 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

Promoter (TATA box)

MAPPING

cloned

Y

linked

status

confirmed

Map	pter - D10S1684 - MAP3K8 - D10S1695 - D10S193 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005204 9 splicing 3096 NP_005195 58 467 - 1993 8226782 397 common Aas 70 specific C-terminal Aas variant 2 - splicing - isoform 2 52 415 - 1993 8226782 397 + 18 C-terminal Aas

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       moderately   liver       lowly Lymphoid/Immune thymus       highly Nervous nerve cranial nerve     moderately Reproductive female system placenta         female system breast mammary gland   lowly Respiratory respiratory tract larynx     highly

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

neonatal, pregnancy

cell cycle

cell cycle, S, checkpoint, G2M

Text	umbilical cord

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a serine proteine kinase domain

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to rattus Map3k8 (94.00 pc)
	homolog to murine Map3k8 (93.36 pc)

Homologene

FAMILY	serine/threonine protein kinase family
	MAP kinase kinase kinase subfamily

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	playing a role in the cell cycle
	can activate both the MAP kinase and JNK kinase pathways
	activates IKappaB kinases and thus induces the nuclear production of NF-KappaB
	promotes the production of TNF-alpha and IL-2 during T lymphocyte activation
	regulates IL8 production, which is markedly reduced in presence of KSR2
	required for TLR4 activation of the MEK/ERK pathway
	able to activate NF-KappaB1 by stimulating proteasome-mediated proteolysis of NF-KappaB1/p105
	may be an important mediator of intracellular mechanotransduction in mesenchymal stem cells
	regulator of T helper cell lineage decisions and important functional role in the regulation of Th1 responses
	functioning as a promoter of apoptosis in ischemia/reperfusion injury
	inducing cell migration upon COX2 expression and Erk1/Erk2 activity
	can phosphorylate histone H3 and thus induces cellular transformation through up-regulation of c-fos transcriptional activity

CELLULAR PROCESS	cell cycle, checkpoint

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

forming a ternary complex with NFKB1 and TNIP2

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor, nucleotide,
	Mg2+ as a cofactor
	ATP binding

protein	NFKB1/p105
	interacting with TNIP2
	IKBKB directly phosphorylated MAP3K8 on three serines, including the critical MAP3K8 phosphorylation following LPS stimulation of macrophages

cell & other

REGULATION

activated by	IL1 stimulated activation of the MAP3K8 catalytic subunit
		through the phosphorylation of Thr290 and Ser62

induced by

IL12 in a Stat4-dependent manner

Other	up-regulated by BCL11B
	autophosphorylated
	activated specifically during the S and G2/M phases of the cell cycle

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in cancer Osaka thyroid

Susceptibility

Variant & Polymorphism

Candidate gene	could be a prognostic factor in breast cancer
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular ischemic injury could be a possible therapeutic target in ischemia/reperfusion injury

ANIMAL & CELL MODELS