MAP3K5 mitogen-activated protein kinase kinase kinase 5 [ Homo sapiens ]

Gene ID: 4217, updated on 19-May-2012

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Summary

Official Symbol: MAP3K5provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase 5provided by HGNC
Primary source: HGNC:6857
Locus tag: RP3-325F22.4
See related: Ensembl:ENSG00000197442; HPRD:03904; MIM:602448; Vega:OTTHUMG00000015647
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ASK1; MEKK5; MAPKKK5
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]

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Genomic context

Location :: 6q22.33

Sequence :: Chromosome: 6; NC_000006.11 (136878187..137113656, complement)

See MAP3K5 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Stimulation of human aortic endothelial cells with TNF-alpha led to an increased expression of p73 protein and a reduction in the levels of p53 involving apoptosis signal-regulating kinase 1 (ASK1).
Title: TNF-α response of vascular endothelial and vascular smooth muscle cells involve differential utilization of ASK1 kinase and p73.
It was found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9.
Title: Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing.
TAK1 and its adapter protein, TAB2, reciprocally regulate both TAK1- and ASK1-mediated signaling pathways to direct the activations of NF-kappaB and AP-1.
Title: Reciprocal inhibition between the transforming growth factor-β-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) mitogen-activated protein kinase kinase kinases and its suppression by TAK1-binding protein 2 (TAB2), an adapter protein for TAK1.
These results suggest that p34 (SEI-1) inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.
Title: p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1.
ZPR9 was found to physically interact with ASK1 through a disulfide linkage;ZPR9 functions as a novel positive regulator of ASK1.
Title: Positive regulation of apoptosis signal-regulating kinase 1 signaling by ZPR9 protein, a zinc finger protein.
a monitoring mechanism of c-Myc and ASK1/p38 against abnormal ribosome biogenesis through controlling the stability and activity of p53 protein
Title: Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest.
knockdown of TXNIP prevented high glucose-induced cell apoptosis and activation of ASK1 may be via reduction of oxidative stress in mesangial cells.
Title: Knockdown of thioredoxin interacting protein attenuates high glucose-induced apoptosis and activation of ASK1 in mouse mesangial cells.
Data show that ASK1 stabilizes SMN protein by inhibiting SMN poly-ubiquitination.
Title: Stabilization of the survival motor neuron protein by ASK1.
iron chelators significantly reduced ASK1-thioredoxin complex formation, resulting in the increased phosphorylation of ASK1, which activates the JNK and p38 pathways
Title: Cellular iron depletion stimulates the JNK and p38 MAPK signaling transduction pathways, dissociation of ASK1-thioredoxin, and activation of ASK1.
TLR4-mediated SphK1 activation was found to be critical for the redox-dependent activation of HIF-1alpha and ASK1, and the prevention of lipopolysaccharide-induced activation of caspase 3 and the expression interleukin-6.
Title: The involvement of sphingosine kinase 1 in LPS-induced Toll-like receptor 4-mediated accumulation of HIF-1α protein, activation of ASK1 and production of the pro-inflammatory cytokine IL-6.

Submit: New GeneRIF Correction See all (96)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Inhibition of ASK1 by HIV-1 Nef leads to the inhibition of both Fas- and TNFalpha-mediated apoptosis, as well as the inhibition of the activation of the downstream c-Jun amino-terminal kinase	PubMed
	nef	HIV-1 Nef inhibits ASK1 catalytic activity by impairing stimulus-coupled release of its normal negative regulator, thioredoxin	PubMed
	nef	HIV-1 Nef binds to ASK1 as demonstrated by GST-pull down and coimmunoprecipitation experiments	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005914.1	NP_002055.1	GLRX	BIND	PubMed	GLRX (GRX) interacts with MAP3K5 (ASK1).
NP_005914.1	NP_002749.2	MAP2K6	BIND	PubMed	MKK6 interacts with ASK1. This interaction was modeled on a demonstrated interaction between human MKK6 and ASK1 from an unspecified species.
NP_005914.1	NP_003320.2	TXN	BIND	PubMed	TXN (TRX) interacts with MAP3K5 (ASK1). This interaction was modeled on a demonstrated interaction between human TXN and MAP3K5 from an unspecified species.
Q99683	P31749	AKT1	HPRD	PubMed
Q99683	P32121	ARRB2	HPRD	PubMed
Q99683	P30304	CDC25A	HPRD	PubMed
Q99683	P38936	CDKN1A	HPRD	PubMed
Q99683	Q5VWQ8	DAB2IP	HPRD	PubMed
Q99683	Q9UER7	DAXX	HPRD	PubMed
Q99683	Q8WTR2	DUSP19	HPRD	PubMed
Q99683	P19525	EIF2AK2	HPRD	PubMed
Q99683	O75460	ERN1	HPRD	PubMed
Q99683	O75293	GADD45B	HPRD	PubMed
Q99683	P35754	GLRX	HPRD	PubMed
Q99683	P09488	GSTM1	HPRD	PubMed
Q99683	Heat shock 70 KD protein 1A	HSPA1A	HPRD	PubMed
Q99683	P08069	IGF1R	HPRD	PubMed
Q99683	P52564	MAP2K6	HPRD	PubMed
Q99683	O14733	MAP2K7	HPRD	PubMed
Q99683	Q9Y2U5	MAP3K2	HPRD	PubMed
Q99683	Q99759	MAP3K3	HPRD	PubMed
Q99683	Q99683	MAP3K5	HPRD	PubMed
Q99683	O95382	MAP3K6	HPRD	PubMed
Q99683	O43318	MAP3K7	HPRD	PubMed
Q99683	Q9UPT6	MAPK8IP3	HPRD	PubMed
Q99683	O75340	PDCD6	HPRD	PubMed
Q99683	P63098	PPP3R1	HPRD	PubMed
Q99683	P53041	PPP5C	HPRD	PubMed
Q99683	P47897	QARS	HPRD	PubMed
Q99683	P04049	RAF1	HPRD	PubMed
Q99683	P31947	SFN	HPRD	PubMed
Q99683	P45379	TNNT2	HPRD	PubMed
Q99683	Q16890	TPD52L1	HPRD	PubMed
Q99683	Q12933	TRAF2	HPRD	PubMed
Q99683	O00463	TRAF5	HPRD	PubMed
Q99683	Q9Y4K3	TRAF6	HPRD	PubMed
Q99683	P10599	TXN	HPRD	PubMed
Q99683	P62258	YWHAE	HPRD	PubMed
Q99683	Q04917	YWHAH	HPRD	PubMed
Q99683	P27348	YWHAQ	HPRD	PubMed
Q99683	P63104	YWHAZ	HPRD	PubMed
BioGRID:110381	BioGRID:106739	ALK	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110381	BioGRID:106901	ARRB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:106902	ARRB2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:107428	CDC25A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110381	BioGRID:107460	CDKN1A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:107777	CREBBP	BioGRID	PubMed	Two-hybrid
BioGRID:110381	BioGRID:107985	DAXX	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:108096	DMD	BioGRID	PubMed	Two-hybrid
BioGRID:110381	BioGRID:126770	DUSP19	BioGRID	PubMed	Affinity Capture-Western; Phenotypic Enhancement
BioGRID:110381	BioGRID:111596	EIF2AK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:108347	EP300	BioGRID	PubMed	Two-hybrid
BioGRID:110381	BioGRID:108391	ERN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:110701	GADD45B	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110381	BioGRID:109007	GLRX	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:109030	GNA12	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:115914	GNA13	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:109199	GSTM1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:200094	Gstm1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110381	BioGRID:109535	HSPA1A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110381	BioGRID:109540	HSPA4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111594	MAP2K6	BioGRID	PubMed	Biochemical Activity; Reconstituted Complex
BioGRID:110381	BioGRID:111595	MAP2K7	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:110381	MAP3K5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:114524	MAP3K6	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110381	BioGRID:112748	MAP3K7	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110381	BioGRID:116774	MAPK8IP3	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:110381	BioGRID:110443	MLL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:110811	NEDD4	BioGRID	PubMed	Biochemical Activity
BioGRID:110381	BioGRID:116915	NEDD4L	BioGRID	PubMed	Biochemical Activity
BioGRID:110381	BioGRID:115333	PDCD6	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Reconstituted Complex
BioGRID:110381	BioGRID:111528	PPP5C	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Phenotypic Suppression
BioGRID:110381	BioGRID:111550	PRKAA2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110381	BioGRID:111552	PRKAB2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110381	BioGRID:111673	PSMC1	BioGRID	PubMed	Affinity Capture-Western; Co-fractionation
BioGRID:110381	BioGRID:111674	PSMC2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111675	PSMC3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111677	PSMC4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111678	PSMC5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111797	QARS	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:111831	RAF1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110381	BioGRID:115160	RB1CC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:198540	Rb1cc1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:112490	SMN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:114203	SOCS1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110381	BioGRID:114488	SOCS3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:115563	STUB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:112983	TNFAIP3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113037	TRAF1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113038	TRAF2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113039	TRAF3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113040	TRAF5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113041	TRAF6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113146	TXN	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110381	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110381	BioGRID:113867	USP9X	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Biochemical Activity; Co-fractionation
BioGRID:110381	BioGRID:113366	YWHAZ	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
MAP kinase kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
cysteine-type endopeptidase activator activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase activity	IDA Inferred from Direct Assay more info
protein kinase binding	IEA Inferred from Electronic Annotation more info
protein phosphatase binding	IPI Inferred from Physical Interaction more info
protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
JNK cascade	IDA Inferred from Direct Assay more info
MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
activation of JUN kinase activity	TAS Traceable Author Statement more info	PubMed
activation of MAPKK activity	IDA Inferred from Direct Assay more info	PubMed
activation of MAPKK activity	TAS Traceable Author Statement more info	PubMed
activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info
hydrogen peroxide-mediated programmed cell death	IDA Inferred from Direct Assay more info
induction of apoptosis by extracellular signals	TAS Traceable Author Statement more info	PubMed
induction of apoptosis by oxidative stress	IDA Inferred from Direct Assay more info
innate immune response	IEA Inferred from Electronic Annotation more info
interspecies interaction between organisms	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info
response to stress	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: mitogen-activated protein kinase kinase kinase 5

Names: mitogen-activated protein kinase kinase kinase 5; ASK-1; MEKK 5; MEK kinase 5; MAP/ERK kinase kinase 5; MAPK/ERK kinase kinase 5; apoptosis signal regulating kinase 1; apoptosis signal-regulating kinase 1

NP_005914.1

EC 2.7.11.25

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011965.1 RefSeqGene

Range

5001..240470

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005923.3 → NP_005914.1 mitogen-activated protein kinase kinase kinase 5

Status: REVIEWED

Source sequence(s)

U67156

Consensus CDS

CCDS5179.1

UniProtKB/Swiss-Prot

Q99683

Related

ENSP00000351908, OTTHUMP00000017275, ENST00000359015, OTTHUMT00000042383

Conserved Domains (3) summary

cd06624
Location:671 – 937
Blast Score: 1500

STKc_ASK; Catalytic domain of the Protein Serine/Threonine Kinase, Apoptosis signal-regulating kinase

smart00220
Location:685 – 937
Blast Score: 721

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam13281
Location:165 – 545
Blast Score: 1321

DUF4071; Domain of unknown function (DUF4071)

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

136878187..137113656, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

134442506..134677689, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL024508.1	CAI20176.1
genomic	AL121933.15	CAI15470.1
genomic	CH471051.2	EAW47942.1
mRNA	AB209093.1	BAD92330.1
mRNA	AK293953.1	BAG57328.1
mRNA	AK294507.1	BAG57723.1
mRNA	AK310942.1	None
mRNA	BC054503.2	AAH54503.1
mRNA	BC088829.1	AAH88829.1
mRNA	D84476.2	BAA12684.2
mRNA	U67156.1	AAC50894.1