MAP3K5 - mitogen-activated protein kinase kinase kinase 5 Gene

Homo sapiens

Also known as ASK1; MEKK5; MAPKKK5

Gene ID: 4217 | Gene type: protein coding

About MAP3K5

Cytogenetic location: 6q23.3 Genomic coordinates (GRCh38): 6:136,557,046-136,793,091 (from NCBI)

This gene has 3 transcripts (splice variants), 206 orthologues and 2 paralogues. Broad expression in adrenal (RPKM 43.3), ovary (RPKM 21.3) and 23 other tissues.

Summary

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 Amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

MAP3K5 Products(10)

mRNA	Protein	Name
XM_011535839.4	XP_011534141.2	mitogen-activated protein kinase kinase kinase 5 isoform X5
XM_017010873.2	XP_016866362.1	mitogen-activated protein kinase kinase kinase 5 isoform X2
XM_017010872.2	XP_016866361.1	mitogen-activated protein kinase kinase kinase 5 isoform X1
XM_047418785.1	XP_047274741.1	mitogen-activated protein kinase kinase kinase 5 isoform X7
XM_017010877.2	XP_016866366.1	mitogen-activated protein kinase kinase kinase 5 isoform X6
XM_047418787.1	XP_047274743.1	mitogen-activated protein kinase kinase kinase 5 isoform X9
XM_047418784.1	XP_047274740.1	mitogen-activated protein kinase kinase kinase 5 isoform X3
XM_047418786.1	XP_047274742.1	mitogen-activated protein kinase kinase kinase 5 isoform X8
NM_005923.4	NP_005914.1	mitogen-activated protein kinase kinase kinase 5
XM_017010875.2	XP_016866364.1	mitogen-activated protein kinase kinase kinase 5 isoform X4

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	Reference	Source
enables ATP binding	IDA IDA: Inferred from direct assay	17210579	GOA
enables JUN kinase kinase kinase activity	IDA IDA: Inferred from direct assay	11959862	GOA
enables MAP kinase kinase kinase activity	IDA IDA: Inferred from direct assay	15983381	GOA
enables identical protein binding	IPI IPI: Inferred from physical interaction	9743501	GOA
enables magnesium ion binding	IDA IDA: Inferred from direct assay	17210579	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	9743501	GOA
enables protein domain specific binding	IPI IPI: Inferred from physical interaction	11096076	GOA
enables protein homodimerization activity	IDA IDA: Inferred from direct assay	11920685	GOA
enables protein kinase activity	IDA IDA: Inferred from direct assay	11096076	GOA
enables protein phosphatase binding	IPI IPI: Inferred from physical interaction	11959862	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in JNK cascade	IDA IDA: Inferred from direct assay	11959862	GOA
involved in JNK cascade	IMP IMP: Inferred from mutant phenotype	22095282	GOA
involved in MAPK cascade	IDA IDA: Inferred from direct assay	17210579	GOA
involved in cellular response to amino acid starvation	IDA IDA: Inferred from direct assay	11096076	GOA
involved in cellular response to hydrogen peroxide	IDA IDA: Inferred from direct assay	20674765	GOA
involved in intrinsic apoptotic signaling pathway in response to oxidative stress	IDA IDA: Inferred from direct assay	21771788	GOA
involved in neuron intrinsic apoptotic signaling pathway in response to oxidative stress	IGI IGI: Inferred from genetic interaction	15983381	GOA
involved in positive regulation of DNA-templated transcription	IDA IDA: Inferred from direct assay	11096076	GOA
involved in positive regulation of JUN kinase activity	IMP IMP: Inferred from mutant phenotype	23000344	GOA
involved in positive regulation of apoptotic process	IDA IDA: Inferred from direct assay	21771788	GOA
involved in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA IDA: Inferred from direct assay	20674765	GOA
involved in positive regulation of protein kinase activity	IDA IDA: Inferred from direct assay	11959862	GOA
involved in protein phosphorylation	IDA IDA: Inferred from direct assay	11096076	GOA
involved in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	23000344	GOA
involved in stress-activated MAPK cascade	IDA IDA: Inferred from direct assay	11096076	GOA

Cellular Component GO Annotation	Evidence	Reference	Source
part of IRE1-TRAF2-ASK1 complex	IDA IDA: Inferred from direct assay	12050113	GOA
located in cytoplasm	IDA IDA: Inferred from direct assay	26095851	GOA
part of protein kinase complex	IDA IDA: Inferred from direct assay	15983381	GOA
part of protein-containing complex	IMP IMP: Inferred from mutant phenotype	11096076	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

MAP3K5 Protein Structure

DUF4071

Pkinase

0
300
600
900
1200
1374 a.a.

Protein Preferred Names

Protein Names

mitogen-activated protein kinase kinase kinase 5

ASK-1	MAP/ERK kinase kinase 5
MAPK/ERK kinase kinase 5	MEK kinase 5
MEKK 5	apoptosis signal-regulating kinase 1

MAP3K5 Protein-protein interaction Information

Type Cross Intra	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	Reference
Cross	MAP3K5	Q99683	Map3k6	Mus musculus	Q9WTR2	Anti Tag CoIP	17210579
Cross	MAP3K5	Q99683	Map3k6	Mus musculus	Q9WTR2	Y2H	17210579
Intra	MAP3K5	Q99683	LRP8	Homo sapiens	Q14114-3	Validated Y2H	32814053
Intra	MAP3K5	Q99683	LRP8	Homo sapiens	Q14114-3	Y2H Pooling	32814053
Intra	MAP3K5	Q99683	LRP8	Homo sapiens	Q14114-3	Y2H Array	32814053
Intra	MAP3K5	Q99683	ZNF622	Homo sapiens	Q969S3	Comigration in Gel	21771788
Intra	MAP3K5	Q99683	ZNF622	Homo sapiens	Q969S3	Anti Bait CoIP	21771788
Intra	MAP3K5	Q99683	ZNF622	Homo sapiens	Q969S3	Pull Down	21771788
Intra	MAP3K5	Q99683	AKT1	Homo sapiens	P31749	Anti Bait CoIP	11154276
Intra	MAP3K5	Q99683	YWHAH	Homo sapiens	Q04917	CoIP	17700517
Intra	MAP3K5	Q99683	YWHAH	Homo sapiens	Q04917	Y2H	15023544
Cross	MAP3K5	Q99683	Vps28	Mus musculus	Q9D1C8	Y2H	14557248
Cross	MAP3K5	Q99683	Vps28	Mus musculus	Q9D1C8	Anti Tag CoIP	14557248
Intra	MAP3K5	Q99683	YWHAZ	Homo sapiens	P63104	Anti Tag CoIP	25852190
Intra	MAP3K5	Q99683	YWHAZ	Homo sapiens	P63104	Pull Down	15023544
Intra	MAP3K5	Q99683	MCRS1	Homo sapiens	Q96EZ8	Anti Bait CoIP	22609355
Intra	MAP3K5	Q99683	HSPB1	Homo sapiens	P04792	Y2H Pooling	32814053
Intra	MAP3K5	Q99683	HSPB1	Homo sapiens	P04792	Validated Y2H	32814053
Intra	MAP3K5	Q99683	HSPB1	Homo sapiens	P04792	Y2H Array	32814053
Intra	MAP3K5	Q99683	TRAF2	Homo sapiens	Q12933	Pull Down	19805025
Intra	MAP3K5	Q99683	TRAF2	Homo sapiens	Q12933	Anti Tag CoIP	19805025
Intra	MAP3K5	Q99683	TRAF2	Homo sapiens	Q12933	Anti Bait CoIP	19805025
Intra	MAP3K5	Q99683	YWHAE	Homo sapiens	P62258	Y2H	15023544
Intra	MAP3K5	Q99683	YWHAB	Homo sapiens	P31946	Anti Bait CoIP	21771788
Intra	MAP3K5	Q99683	YWHAB	Homo sapiens	P31946	Y2H	15023544
Intra	MAP3K5	Q99683	CIB1	Homo sapiens	Q99828	Anti Bait CoIP	19805025
Intra	MAP3K5	Q99683	SMN1	Homo sapiens	Q16637	Anti Tag CoIP	21496457
Intra	MAP3K5	Q99683	MAP3K5	Homo sapiens	Q99683	CoIP	9743501
Intra	MAP3K5	Q99683	MAP3K5	Homo sapiens	Q99683	GMS	17937911
Intra	MAP3K5	Q99683	MAP3K5	Homo sapiens	Q99683	Solution Sedimentation	17937911
Intra	MAP3K5	Q99683	MAP3K5	Homo sapiens	Q99683	Anti Tag CoIP	19805025
Intra	MAP3K5	Q99683	MAP2K3	Homo sapiens	P46734	Anti Tag CoIP	19805025
Intra	MAP3K5	Q99683	MAP2K3	Homo sapiens	P46734	Anti Bait CoIP	21771788
Intra	MAP3K5	Q99683	MAP3K5	Homo sapiens	Q99683	X-Ray Diffraction	17937911
Intra	MAP3K5	Q99683	HTRA2	Homo sapiens	O43464	Validated Y2H	32814053
Intra	MAP3K5	Q99683	HTRA2	Homo sapiens	O43464	Y2H Array	32814053
Intra	MAP3K5	Q99683	HTRA2	Homo sapiens	O43464	Y2H Pooling	32814053
Intra	MAP3K5	Q99683	TXN	Homo sapiens	P10599	Anti Bait CoIP	19805025
Intra	MAP3K5	Q99683	TXN	Homo sapiens	P10599	Anti Bait CoIP	21771788
Intra	MAP3K5	Q99683	ARRB1	Homo sapiens	P49407	Anti Tag CoIP	19782076
Intra	MAP3K5	Q99683	PRPS1	Homo sapiens	P60891	Y2H Array	32814053
Intra	MAP3K5	Q99683	PRPS1	Homo sapiens	P60891	Validated Y2H	32814053
Intra	MAP3K5	Q99683	PRPS1	Homo sapiens	P60891	Y2H Pooling	32814053
Intra	MAP3K5	Q99683	PPP3R1	Homo sapiens	P63098	Anti Bait CoIP	16648474

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Diseases

Diseases

Alias

Fatty Liver Disease

Alcoholic Fatty Liver	Fatty Liver
Fatty Liver, Alcoholic	Fatty Change Of Liver
Hepatic Lipidosis	Steatosis Of Liver
Fatty Liver Alcoholic	Steatohepatitis
Etoh Fatty Liver	Etoh Fatty Liver Metamorphosis
Fatty Etoh Liver Necrosis

Glottis Squamous Cell Carcinoma

Epidermoid Carcinoma Of The Glottis

Squamous Cell Carcinoma Of Glottis

Non-Alcoholic Fatty Liver Disease

Fatty Liver	Non-Alcoholic Fatty Liver
Nafld	Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis	Steatosis
Nafl	Nash
Non-Alcoholic Steatohepatitis	Susceptibility To Nonalcoholic Fatty Liver Disease
Steatohepatitis	Fatty Degeneration
Non-Alcoholic Fatty Liver Disease Without Mention Of Non-Alcoholic Steatohepatitis	Nafld Without Nash
Nafld Without Mention Of Nash

Amyotrophic Lateral Sclerosis 1

Amyotrophic Lateral Sclerosis	ALS
Lou Gehrig Disease	Amyotrophic Lateral Sclerosis Type 1
Charcot Disease	ALS1
Amyotrophic Lateral Sclerosis, Susceptibility To	Fals
Lou Gehrig'S Disease	Mnd
Motor Neuron Disease	Familial Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 1, Familial	Amyotrophic Lateral Sclerosis 1, Autosomal Dominant
Motor Neuron Disease, Bulbar	Motor Neurone Disease
Amyotrophic Lateral Sclerosis With Dementia	Dementia With Amyotrophic Lateral Sclerosis
Motor Neuron Disease, Amyotrophic Lateral Sclerosis	Sclerosis, Lateral, Amyotrophic
Sclerosis, Lateral, Amyotrophic, Type 1	Amyotrophic Sclerosis
Als - [Amyotrophic Lateral Sclerosis]	Wasting Palsy
Amyotrophic Paralysis	Amyotrophy Lateral Sclerosis
Wasting Paralysis	Spinal Progressive Amyotrophy
Progressive Atrophic Paralysis

Neural Tube Defects

Spina Bifida	Neural Tube Defect
NTD	Neural Tube Defects, Susceptibility To
Spinal Dysraphism	Spina Bifida, Susceptibility To
Rachischisis	Cleft Spine
Open Spine	Hydrocele Spinalis
Neural Tube Defect Nos	Sb - [Spina Bifida]
Spinal Hernia Nos	Spinal Fissure Nos

Pyriform Sinus Cancer

Malignant Neoplasm Of Pyriform Fossa	Malignant Neoplasm Of The Pyriform Fossa
Malignant Tumor Of Pyriform Fossa

Alzheimer Disease, Familial, 1

Alzheimer Disease	Alzheimer'S Disease
Presenile And Senile Dementia	AD1
Alzheimer Disease, Susceptibility To	Alzheimer Disease, Late-Onset, Susceptibility To
Alzheimer Disease 1, Familial	AD
Familial Alzheimer Disease	Alzheimer Disease, Late-Onset
Alzheimers Dementia	Alzheimer Dementia
Alzheimer Sclerosis	Alzheimer Syndrome
Alzheimer-Type Dementia	Dat
Primary Senile Degenerative Dementia	Sdat
Alzheimer Disease 1	Autosomal Dominant Alzheimer Disease
Early-Onset Alzheimer Disease With Cerebral Amyloid Angiopathy	Late Onset Alzheimer Disease
Alzheimers Disease	Alzheimer Disease, Early-Onset, With Cerebral Amyloid Angiopathy
Late-Onset Alzheimers Disease	Alzheimer'S Disease Pathway Kegg
Dementia Due To Alzheimer'S Disease	Alzheimer Disease Type 1
Alzheimers

Glioblastoma Classical Subtype

Liver Disease

Liver Failure	Liver Diseases
Abnormality Of The Liver	Liver Dysfunction
Disorder Of Liver	Hepatic Disorder
Hepatic Disease	Disease Of Bilirubin Metabolism
Disorder Of Bilirubin Metabolism	Liver Decompensation
Liver Function Failure	Hepatic Failure Nos
Liver Failure Nos	End Stage Liver Disease
Decompensated Liver Failure	Decompensation Of Liver Function
Hepatic Decompensation	Hepatic Insufficiency
Liver Cell Necrosis With Hepatic Failure	Liver Insufficiency
Decompensated Liver Disease	End Stage Liver Failure
Liver Necrosis With Hepatic Failure

Diabetes Mellitus

Diabetes

Partial Third-Nerve Palsy

Partial Third Nerve Palsy	Third Nerve Palsy With Pupil Sparing
Third Or Oculomotor Nerve Palsy, Partial	Oculomotor Nerve Diseases
Oculomotor Nerve Paralysis

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

Bioactive Molecules (3)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-RS08058	MAP3K5 Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-RS08059	Map3k5 Mouse Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-RS08060	Map3k5 Rat Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Mus musculus	MAP3K5	MGD	MGI:1346876
Macaca mulatta	MAP3K5	VGNC	VGNC:74495
Canis familiaris	MAP3K5	VGNC	VGNC:42975
Felis catus	MAP3K5	VGNC	VGNC:68159
Rattus norvegicus	MAP3K5	RGD	RGD:1306565
Bos taurus	MAP3K5	VGNC	VGNC:31198
Others	MAP3K5	NCBI

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