MAP3K5 - mitogen-activated protein kinase kinase kinase 5 Gene

Also Known as ASK1; MEKK5; MAPKKK5

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 4217

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	References	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	References	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	References	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	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
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

MAP3K5 Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P80020	ASK1 Antibody (YA609)	WB, ICC/IF, IHC-P, FC	Human, Mouse
HY-P80549	ASK1 Antibody	WB, IHC-P, ICC/IF, FC	Human, Mouse
HY-P80792	Phospho-ASK1 (Ser966) Antibody	WB, IHC-P	Human, Mouse, Rat
HY-P85046	ASK1 Antibody (YA4738)	WB, IHC-P, ICC/IF, FC, ELISA	Human
HY-P86322	ASK1 Antibody (YA6014)	WB, IHC-P, ICC/IF, IP, ELISA	Human, Mouse

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

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 Set	/	Unkown
HY-RS08059	Map3k5 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS08060	Map3k5 Rat Pre-designed siRNA Set A	Pre-designed Set	/	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