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MAP3K8 - mitogen-activated protein kinase kinase kinase 8 Gene

Also Known as COT; EST; ESTF; TPL2; AURA2; MEKK8; Tpl-2; c-COT

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 1326

About MAP3K8

Cytogenetic location: 10p11.23 Genomic coordinates (GRCh38): 10:30,434,021-30,461,833 (from NCBI)

This gene has 7 transcripts (splice variants), 199 orthologues, 35 paralogues and is associated with 1 phenotype. Broad expression in bone marrow (RPKM 18.4), appendix (RPKM 6.8) and 17 other tissues.

Summary

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, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

MAP3K8 Products (9)

mRNA	Protein	Name
XM_017015714.2	XP_016871203.1	mitogen-activated protein kinase kinase kinase 8 isoform X2
XM_017015710.1	XP_016871199.1	mitogen-activated protein kinase kinase kinase 8 isoform X1
XM_047424623.1	XP_047280579.1	mitogen-activated protein kinase kinase kinase 8 isoform X1
NM_005204.4	NP_005195.2	mitogen-activated protein kinase kinase kinase 8
XM_047424622.1	XP_047280578.1	mitogen-activated protein kinase kinase kinase 8 isoform X1
NM_001320961.2	NP_001307890.1	mitogen-activated protein kinase kinase kinase 8
XM_017015709.3	XP_016871198.1	mitogen-activated protein kinase kinase kinase 8 isoform X1
XM_047424624.1	XP_047280580.1	mitogen-activated protein kinase kinase kinase 8 isoform X1
NM_001244134.1	NP_001231063.1	mitogen-activated protein kinase kinase kinase 8

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables MAP kinase kinase kinase activity	IDA IDA: Inferred from direct assay	1833717	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	12832462	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in MAPK cascade	IDA IDA: Inferred from direct assay	1833717	GOA
involved in positive regulation of inflammatory response	IDA IDA: Inferred from direct assay	16424369	GOA

Cellular Component GO Annotation	Evidence	References	Source
is active in cytoplasm	IDA IDA: Inferred from direct assay	1833717	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

MAP3K8 Protein Structure

Pkinase

0
100
200
300
400
467 a.a.

Protein Preferred Names	Protein Names
mitogen-activated protein kinase kinase kinase 8	Ewing sarcoma transformant augmented in rheumatoid arthritis 2 cot (cancer Osaka thyroid) oncogene proto-oncogene c-Cot proto-oncogene serine/threoine protein kinase tumor progression locus 2

MAP3K8 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	MAP3K8	P41279	NFKB1	Homo sapiens	P19838	Anti Tag CoIP	25852190
Intra	MAP3K8	P41279	NFKB1	Homo sapiens	P19838	Anti Tag CoIP	12832462
Intra	MAP3K8	P41279	NFKB1	Homo sapiens	P19838	Y2H	21988832
Intra	MAP3K8	P41279	NFKB1	Homo sapiens	P19838	Pull Down	12832462
Intra	MAP3K8	P41279	NFKB2	Homo sapiens	Q00653	TAP	14743216
Intra	MAP3K8	P41279	NFKB2	Homo sapiens	Q00653	Anti Tag CoIP	25852190
Intra	MAP3K8	P41279	HSP90AB1	Homo sapiens	P08238	Anti Tag CoIP	22939624
Intra	MAP3K8	P41279	TNIP2	Homo sapiens	Q8NFZ5	Pull Down	15169888
Intra	MAP3K8	P41279	TNIP2	Homo sapiens	Q8NFZ5	Anti Bait CoIP	15169888
Intra	MAP3K8	P41279	TNIP2	Homo sapiens	Q8NFZ5	Anti Tag CoIP	25852190
Intra	MAP3K8	P41279	PIN1	Homo sapiens	Q13526	Y2H	24265246
Intra	MAP3K8	P41279	PIN1	Homo sapiens	Q13526	Pull Down	24265246
Intra	MAP3K8	P41279	PIN1	Homo sapiens	Q13526	Anti Tag CoIP	24265246

Cross: Cross-species interaction Intra: Intraspecies interaction

Recombinant MAP3K8 Proteins

Cat. No.	Product Name	Accession	Purity
HY-P75921	MAP3K8/TPL-2 Protein, Human (sf9, GST)	P41279 (M30-R397)	≥ 90%, as determined by reducing SDS-PAGE.

Related Diseases

Diseases	Alias
Ewing Sarcoma	Neuroepithelioma Ewing'S Tumor Ewings Sarcoma Ewing'S Sarcoma Peripheral Neuroepithelioma Primitive Neuroectodermal Tumor ES Ewings Sarcoma-Primitive Neuroectodermal Tumor Localized Peripheral Primitive Neuroectodermal Tumor Peripheral Primitive Neuroectodermal Tumor Ewing Tumor Sarcoma, Ewing'S Extraosseous Ewing Tumor Askin Tumor Ewing'S Family Localized Tumor Ewing'S Sarcoma/Peripheral Primitive Neuroectodermal Tumor Localized Ewing Sarcoma Localized Ewing'S Sarcoma Localized Ewing'S Sarcoma/Peripheral Primitive Neuroectodermal Tumor Localized Ewing'S Tumor Pnet Of Thoracopulmonary Region Ewing Family Of Tumors Tumor Of The Ewing Family Skeletal Ewing Sarcoma Osseous Ewing Sarcoma Ppnet Peripheral Pnet Extraskeletal Ewing Sarcoma Eoe Extraosseous Ewing Sarcoma Extraskeletal Ewing Tumor Esft Ewing Sarcoma Family Of Tumors Pne Pnet Pnet Of The Chest Wall Sarcoma, Ewing Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumor, Primitive Disorder Of Eye Askin'S Tumor Extraosseous Ewings Sarcoma-Primitive Neuroepithelial Tumor Neuroepithelioma, Peripheral
Rheumatoid Arthritis	RA Arthritis, Rheumatoid Rheumatoid Arthritis, Susceptibility To Arthritis Or Polyarthritis, Rheumatic Atrophic Arthritis Rheumatism Arthritis Rheumatoid Polyarthritis
Rasopathy	Ras/Mitogen-Activated Protein Kinase Syndrome
Lung Cancer	Lung Carcinoma Non-Small Cell Lung Carcinoma Lung Cancer, Protection Against Lung Cancer, Susceptibility To Adenocarcinoma Of Lung, Somatic Nonsmall Cell Lung Cancer Adenocarcinoma Of Lung, Response To Tyrosine Kinase Inhibitor In Lung Neoplasm Carcinoma Of Lung Lung Non-Small Cell Carcinoma Non-Small Cell Lung Cancer Nsclc Lung Neoplasms Malignant Neoplasm Of Lung Alveolar Cell Carcinoma Nonsmall Cell Lung Cancer, Somatic Nonsmall Cell Lung Cancer, Response To Tyrosine Kinase Inhibitor In Nonsmall Cell Lung Cancer, Susceptibility To Lung Cancer, Somatic Lung Cancer, Resistance To Cancer Of Lung Cancer Of Bronchus Cancer Of The Lung Lung Malignancies Lung Malignant Tumors Malignant Lung Tumor Malignant Tumor Of Lung Pulmonary Cancer Pulmonary Carcinoma Pulmonary Neoplasms Respiratory Carcinoma LNCR Adenocarcinoma Of Lung Neoplasm Of Lung Cancer Lung Carcinoma Non-Small Cell Lung Carcinoma, Non-Small-Cell Lung Lung Cancers Lung Carcinomas Cancer, Lung Cancer, Lung, Non-Small Cell Primary Malignant Neoplasm Of Lung Bronchioloalveolar Adenocarcinoma
Spitzoid Melanoma	Atypical Spitz Nevus

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (7)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-12358	Tpl2 Kinase Inhibitor 1	Inhibitor	99.42%	Unkown
HY-124953	7,3',4'-Trihydroxyisoflavone		99.83%	Unkown
HY-32018	Cot inhibitor-2	Inhibitor	99.65%	Unkown
HY-RS08067	Map3k8 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS08068	Map3k8 Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-12358A	Tpl2 Kinase Inhibitor 1 hydrochloride	Inhibitor	/	Unkown
HY-RS08066	MAP3K8 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Felis catus	MAP3K8	VGNC	VGNC:97497
Bos taurus	MAP3K8	VGNC	VGNC:31202
Canis familiaris	MAP3K8	VGNC	VGNC:42979
Rattus norvegicus	MAP3K8	RGD	RGD:620969
Mus musculus	MAP3K8	MGD	MGI:1346878
Macaca mulatta	MAP3K8	VGNC	VGNC:81464
Others	MAP3K8	NCBI