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MAP3K8 (mitogen-activated protein kinase kinase kinase 8)

Gene

1326

Mitogen-activated protein kinase kinase kinase 8

MAP3K8

AURA2, COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT

10p11.23

This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases,

Show/Hide all(203)

miRTarBase ID	miRNA	Experiments	Reference
MIRT001074	hsa-miR-370-3p	Luciferase reporter assay, Western blot	17621267
MIRT001074	hsa-miR-370-3p	Luciferase reporter assay	17621267
MIRT007200	hsa-miR-375	Luciferase reporter assay	23430746
MIRT007200	hsa-miR-375	Luciferase reporter assay	23430746
MIRT016056	hsa-miR-374b-5p	Sequencing	20371350
MIRT017102	hsa-miR-335-5p	Microarray	18185580
MIRT001074	hsa-miR-370-3p	Other	17621267
MIRT022367	hsa-miR-124-3p	Microarray	18668037
MIRT051038	hsa-miR-17-5p	CLASH	23622248
MIRT053364	hsa-miR-9-5p	Microarray, qRT-PCR	23798388
MIRT731324	mmu-miR-509-3p	Luciferase reporter assay	27001999
MIRT731324	mmu-miR-509-3p	Luciferase reporter assay	27001999
MIRT731324	mmu-miR-509-3p	Luciferase reporter assay	27001999
MIRT731324	mmu-miR-509-3p	Luciferase reporter assay	27001999
MIRT731688	hsa-miR-144-3p	Luciferase reporter assay, qRT-PCR, Western blot	27717821
MIRT731688	hsa-miR-144-3p	Luciferase reporter assay, qRT-PCR, Western blot	27717821
MIRT007200	hsa-miR-375	Western blot	28186962
MIRT1129092	hsa-miR-101	CLIP-seq
MIRT1129093	hsa-miR-106a	CLIP-seq
MIRT1129094	hsa-miR-106b	CLIP-seq
MIRT1129095	hsa-miR-1257	CLIP-seq
MIRT1129096	hsa-miR-128	CLIP-seq
MIRT1129097	hsa-miR-132	CLIP-seq
MIRT1129098	hsa-miR-1323	CLIP-seq
MIRT1129099	hsa-miR-144	CLIP-seq
MIRT1129100	hsa-miR-17	CLIP-seq
MIRT1129101	hsa-miR-181a	CLIP-seq
MIRT1129102	hsa-miR-181b	CLIP-seq
MIRT1129103	hsa-miR-181c	CLIP-seq
MIRT1129104	hsa-miR-181d	CLIP-seq
MIRT1129105	hsa-miR-2052	CLIP-seq
MIRT1129106	hsa-miR-20a	CLIP-seq
MIRT1129107	hsa-miR-20b	CLIP-seq
MIRT1129108	hsa-miR-212	CLIP-seq
MIRT1129109	hsa-miR-214	CLIP-seq
MIRT1129110	hsa-miR-23a	CLIP-seq
MIRT1129111	hsa-miR-23b	CLIP-seq
MIRT1129112	hsa-miR-23c	CLIP-seq
MIRT1129113	hsa-miR-3163	CLIP-seq
MIRT1129114	hsa-miR-3166	CLIP-seq
MIRT1129115	hsa-miR-3612	CLIP-seq
MIRT1129116	hsa-miR-3619-5p	CLIP-seq
MIRT1129117	hsa-miR-3671	CLIP-seq
MIRT1129118	hsa-miR-3918	CLIP-seq
MIRT1129119	hsa-miR-4262	CLIP-seq
MIRT1129120	hsa-miR-4291	CLIP-seq
MIRT1129121	hsa-miR-4310	CLIP-seq
MIRT1129122	hsa-miR-432	CLIP-seq
MIRT1129123	hsa-miR-4443	CLIP-seq
MIRT1129124	hsa-miR-448	CLIP-seq
MIRT1129125	hsa-miR-4484	CLIP-seq
MIRT1129126	hsa-miR-4717-3p	CLIP-seq
MIRT1129127	hsa-miR-494	CLIP-seq
MIRT1129128	hsa-miR-499-3p	CLIP-seq
MIRT1129129	hsa-miR-499a-3p	CLIP-seq
MIRT1129130	hsa-miR-519a	CLIP-seq
MIRT1129131	hsa-miR-519b-3p	CLIP-seq
MIRT1129132	hsa-miR-519c-3p	CLIP-seq
MIRT1129133	hsa-miR-519d	CLIP-seq
MIRT1129134	hsa-miR-548an	CLIP-seq
MIRT1129135	hsa-miR-548o	CLIP-seq
MIRT1129136	hsa-miR-548q	CLIP-seq
MIRT1129137	hsa-miR-650	CLIP-seq
MIRT1129138	hsa-miR-761	CLIP-seq
MIRT1129139	hsa-miR-922	CLIP-seq
MIRT1129140	hsa-miR-93	CLIP-seq
MIRT1129092	hsa-miR-101	CLIP-seq
MIRT2036732	hsa-miR-1197	CLIP-seq
MIRT2036733	hsa-miR-1245b-3p	CLIP-seq
MIRT2036734	hsa-miR-1297	CLIP-seq
MIRT2036735	hsa-miR-135a	CLIP-seq
MIRT2036736	hsa-miR-135b	CLIP-seq
MIRT2036737	hsa-miR-137	CLIP-seq
MIRT1129099	hsa-miR-144	CLIP-seq
MIRT1129105	hsa-miR-2052	CLIP-seq
MIRT2036738	hsa-miR-21	CLIP-seq
MIRT2036739	hsa-miR-221	CLIP-seq
MIRT2036740	hsa-miR-222	CLIP-seq
MIRT2036741	hsa-miR-26a	CLIP-seq
MIRT2036742	hsa-miR-26b	CLIP-seq
MIRT2036743	hsa-miR-3117-3p	CLIP-seq
MIRT2036744	hsa-miR-3117-5p	CLIP-seq
MIRT1129114	hsa-miR-3166	CLIP-seq
MIRT2036745	hsa-miR-362-5p	CLIP-seq
MIRT2036746	hsa-miR-3677-5p	CLIP-seq
MIRT2036747	hsa-miR-370	CLIP-seq
MIRT2036748	hsa-miR-382	CLIP-seq
MIRT2036749	hsa-miR-4267	CLIP-seq
MIRT2036750	hsa-miR-4273	CLIP-seq
MIRT2036751	hsa-miR-4282	CLIP-seq
MIRT1129120	hsa-miR-4291	CLIP-seq
MIRT1129121	hsa-miR-4310	CLIP-seq
MIRT2036752	hsa-miR-4465	CLIP-seq
MIRT2036753	hsa-miR-4520a-3p	CLIP-seq
MIRT2036754	hsa-miR-4520b-3p	CLIP-seq
MIRT2036755	hsa-miR-4662a-5p	CLIP-seq
MIRT2036756	hsa-miR-4677-5p	CLIP-seq
MIRT2036757	hsa-miR-4704-5p	CLIP-seq
MIRT2036758	hsa-miR-4735-5p	CLIP-seq
MIRT2036759	hsa-miR-4760-3p	CLIP-seq
MIRT2036760	hsa-miR-500b	CLIP-seq
MIRT2036761	hsa-miR-501-5p	CLIP-seq
MIRT2036762	hsa-miR-520d-5p	CLIP-seq
MIRT2036763	hsa-miR-524-5p	CLIP-seq
MIRT2036764	hsa-miR-548n	CLIP-seq
MIRT2036765	hsa-miR-548v	CLIP-seq
MIRT2036766	hsa-miR-554	CLIP-seq
MIRT2036767	hsa-miR-576-5p	CLIP-seq
MIRT2036768	hsa-miR-587	CLIP-seq
MIRT2036769	hsa-miR-590-5p	CLIP-seq
MIRT2036770	hsa-miR-626	CLIP-seq
MIRT2036771	hsa-miR-651	CLIP-seq
MIRT2036772	hsa-miR-668	CLIP-seq
MIRT1129139	hsa-miR-922	CLIP-seq
MIRT2036773	hsa-miR-935	CLIP-seq
MIRT2036732	hsa-miR-1197	CLIP-seq
MIRT2036733	hsa-miR-1245b-3p	CLIP-seq
MIRT1129097	hsa-miR-132	CLIP-seq
MIRT2036735	hsa-miR-135a	CLIP-seq
MIRT2036736	hsa-miR-135b	CLIP-seq
MIRT2036737	hsa-miR-137	CLIP-seq
MIRT2036738	hsa-miR-21	CLIP-seq
MIRT1129108	hsa-miR-212	CLIP-seq
MIRT1129109	hsa-miR-214	CLIP-seq
MIRT2036739	hsa-miR-221	CLIP-seq
MIRT2036740	hsa-miR-222	CLIP-seq
MIRT2266937	hsa-miR-296-5p	CLIP-seq
MIRT2036743	hsa-miR-3117-3p	CLIP-seq
MIRT2036744	hsa-miR-3117-5p	CLIP-seq
MIRT1129114	hsa-miR-3166	CLIP-seq
MIRT1129116	hsa-miR-3619-5p	CLIP-seq
MIRT2266938	hsa-miR-3662	CLIP-seq
MIRT2036746	hsa-miR-3677-5p	CLIP-seq
MIRT2036747	hsa-miR-370	CLIP-seq
MIRT2266939	hsa-miR-3914	CLIP-seq
MIRT2036749	hsa-miR-4267	CLIP-seq
MIRT1129120	hsa-miR-4291	CLIP-seq
MIRT2036757	hsa-miR-4704-5p	CLIP-seq
MIRT2036758	hsa-miR-4735-5p	CLIP-seq
MIRT2266940	hsa-miR-4738-3p	CLIP-seq
MIRT2036759	hsa-miR-4760-3p	CLIP-seq
MIRT1129127	hsa-miR-494	CLIP-seq
MIRT2266941	hsa-miR-548g	CLIP-seq
MIRT2036765	hsa-miR-548v	CLIP-seq
MIRT2036766	hsa-miR-554	CLIP-seq
MIRT2036767	hsa-miR-576-5p	CLIP-seq
MIRT2036768	hsa-miR-587	CLIP-seq
MIRT2036769	hsa-miR-590-5p	CLIP-seq
MIRT2036770	hsa-miR-626	CLIP-seq
MIRT2036771	hsa-miR-651	CLIP-seq
MIRT2036772	hsa-miR-668	CLIP-seq
MIRT1129138	hsa-miR-761	CLIP-seq
MIRT1129139	hsa-miR-922	CLIP-seq
MIRT2036732	hsa-miR-1197	CLIP-seq
MIRT2036733	hsa-miR-1245b-3p	CLIP-seq
MIRT2036735	hsa-miR-135a	CLIP-seq
MIRT2036736	hsa-miR-135b	CLIP-seq
MIRT2036737	hsa-miR-137	CLIP-seq
MIRT2566512	hsa-miR-200b	CLIP-seq
MIRT2566513	hsa-miR-200c	CLIP-seq
MIRT2036738	hsa-miR-21	CLIP-seq
MIRT2036739	hsa-miR-221	CLIP-seq
MIRT2036740	hsa-miR-222	CLIP-seq
MIRT2566514	hsa-miR-3074-5p	CLIP-seq
MIRT2036743	hsa-miR-3117-3p	CLIP-seq
MIRT2036744	hsa-miR-3117-5p	CLIP-seq
MIRT2566515	hsa-miR-3182	CLIP-seq
MIRT2036746	hsa-miR-3677-5p	CLIP-seq
MIRT2036747	hsa-miR-370	CLIP-seq
MIRT2566516	hsa-miR-371-5p	CLIP-seq
MIRT2566517	hsa-miR-371b-5p	CLIP-seq
MIRT2036749	hsa-miR-4267	CLIP-seq
MIRT2566518	hsa-miR-429	CLIP-seq
MIRT2036755	hsa-miR-4662a-5p	CLIP-seq
MIRT2566519	hsa-miR-4677-3p	CLIP-seq
MIRT2566520	hsa-miR-4679	CLIP-seq
MIRT2566521	hsa-miR-4680-3p	CLIP-seq
MIRT2566522	hsa-miR-4680-5p	CLIP-seq
MIRT2036757	hsa-miR-4704-5p	CLIP-seq
MIRT2566523	hsa-miR-4722-3p	CLIP-seq
MIRT2566524	hsa-miR-4724-5p	CLIP-seq
MIRT2036758	hsa-miR-4735-5p	CLIP-seq
MIRT2036759	hsa-miR-4760-3p	CLIP-seq
MIRT2036765	hsa-miR-548v	CLIP-seq
MIRT2036766	hsa-miR-554	CLIP-seq
MIRT2036767	hsa-miR-576-5p	CLIP-seq
MIRT2036769	hsa-miR-590-5p	CLIP-seq
MIRT2036770	hsa-miR-626	CLIP-seq
MIRT2036771	hsa-miR-651	CLIP-seq
MIRT2036772	hsa-miR-668	CLIP-seq
MIRT2036773	hsa-miR-935	CLIP-seq
MIRT2036733	hsa-miR-1245b-3p	CLIP-seq
MIRT2036735	hsa-miR-135a	CLIP-seq
MIRT2036736	hsa-miR-135b	CLIP-seq
MIRT2036743	hsa-miR-3117-3p	CLIP-seq
MIRT2036746	hsa-miR-3677-5p	CLIP-seq
MIRT2036747	hsa-miR-370	CLIP-seq
MIRT2036758	hsa-miR-4735-5p	CLIP-seq
MIRT2036759	hsa-miR-4760-3p	CLIP-seq
MIRT2036767	hsa-miR-576-5p	CLIP-seq
MIRT2036770	hsa-miR-626	CLIP-seq
MIRT2036771	hsa-miR-651	CLIP-seq
MIRT2036772	hsa-miR-668	CLIP-seq

Show/Hide all(13)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000186	Process	Activation of MAPKK activity	IEA
GO:0000287	Function	Magnesium ion binding	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	TAS	8226782
GO:0004709	Function	MAP kinase kinase kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	12832462, 14743216, 15169888, 21988832, 22939624, 24265246, 25609649, 25852190
GO:0005524	Function	ATP binding	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IEA
GO:0007049	Process	Cell cycle	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0051403	Process	Stress-activated MAPK cascade	TAS
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS

MIM	HGNC	e!Ensembl
191195	6860	ENSG00000107968

Protein

UniProt ID

P41279

Protein name

Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2)

Protein function

Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulati

PDB

4Y83 , 4Y85 , 5IU2

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00069	Pkinase	139 → 388	Protein kinase domain	Domain

Sequence

MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERS
KSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGR
YQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVE
IQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKG
LDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVIL
CRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPG
MRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELP
ENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG

Sequence length

467

Interactions

View interactions

	KEGG		Reactome
	MAPK signaling pathway Toll-like receptor signaling pathway T cell receptor signaling pathway TNF signaling pathway		CD28 dependent PI3K/Akt signaling MAP3K8 (TPL2)-dependent MAPK1/3 activation

Associated diseases

Show/Hide Causal Diseases (3)

Causal
Disease name	Disease term	dbSNP ID	References
Inflammatory bowel disease	Inflammatory Bowel Diseases	rs137853579, rs137853580, rs121909601, rs149491038, rs368287711, rs387907326, rs587777338, rs758439420, rs139868987, rs750447828, rs368138379, rs1329427406, rs1264862631, rs1192830343, rs1373354533, rs1419560997, rs1591263883, rs1989014468	23128233, 28067908
Lung adenocarcinoma	Bronchioloalveolar Adenocarcinoma	rs28934576, rs121913530, rs397516975, rs587776805, rs121913469, rs121913364, rs121913351, rs121913366, rs397516896, rs397516977, rs397516981, rs397517127, rs121913344, rs727504233, rs121913370, rs760043106, rs1057519788, rs1131692238, rs1131692237, rs1554350382
Lung cancer	Malignant neoplasm of lung	rs121913530, rs121913529, rs878855122, rs1057519784, rs770315135

Show/Hide Unknown Diseases (3)

Unknown
Disease name	Disease term	dbSNP ID	References
Crohn disease	Crohn Disease	rs2066847, rs2066844, rs886052047, rs5743265, rs111608429, rs104895438	28067908, 26192919
Lung neoplasms	Lung Neoplasms
Myocardial ischemia	Myocardial Ischemia		16214533

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