MAP3K6 mitogen-activated protein kinase kinase kinase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP3K6provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase 6provided by HGNC
Primary source: HGNC:HGNC:6858
See related: Ensembl:ENSG00000142733 MIM:604468; Vega:OTTHUMG00000004631
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: ASK2; MEKK6; MAPKKK6
Summary: This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression: Broad expression in skin (RPKM 18.7), fat (RPKM 11.6) and 21 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 1p36.11

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (27355179..27368037, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (27681670..27693558, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Data show that the MAPKKK6 ASK2, a modulator of MAPKKK5 ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing interferon-beta (IFNB) expression.
Title: The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response.
MAP3K6 acts as a tumor suppressor, and studies showing the presence of somatic mutations in MAP3K6 in non-hereditary gastric cancers and gastric cancer cell lines, point towards MAP3K6 variants as a predisposing factor for familial gastric cancer
Title: Germline mutations in MAP3K6 are associated with familial gastric cancer.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
regulation of VEGF by MAP3K6 may play a crucial role in both angiogenesis and tumorigenesis.
Title: Mitogen-activated protein 3 kinase 6 mediates angiogenic and tumorigenic effects via vascular endothelial growth factor expression.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1.
Title: Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystem (from WikiPathways)
Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystemThe hepatic ANGPTL8 (Angiopoietin Like Protein 8) regulatory pathway represents an up-to-date curated interactive pathway for all of the interactions from the known regulators of ANGPTL8 and updated ...
Insulin Signaling, organism-specific biosystem (from WikiPathways)
Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
MAPK (JNK) signaling, organism-specific biosystem (from KEGG)
MAPK (JNK) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
MAPK (JNK) signaling, conserved biosystem (from KEGG)
MAPK (JNK) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
MAPK (p38) signaling, organism-specific biosystem (from KEGG)
MAPK (p38) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
MAPK (p38) signaling, conserved biosystem (from KEGG)
MAPK (p38) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
MAPK Signaling Pathway, organism-specific biosystem (from WikiPathways)
MAPK Signaling Pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, organism-specific biosystem (from KEGG)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, conserved biosystem (from KEGG)
MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
p38 MAPK signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
p38 MAPK signaling pathway, organism-specific biosystem
p38 MAPK signaling pathway

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH94083 (e-PCR)
- UniSTS:89749

NoName (e-PCR)
- UniSTS:484507

Homology

Homologs of the MAP3K6 gene: The MAP3K6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 143 organisms have orthologs with human gene MAP3K6
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
MAP kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
MAP kinase kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
activation of JUN kinase activity	TAS Traceable Author Statement more info	PubMed
activation of MAPKK activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activation of MAPKK activity	IEA Inferred from Electronic Annotation more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
intracellular	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 6

Names: apoptosis signal-regulating kinase 2

NP_001284538.1

EC 2.7.11.25

NP_004663.3

EC 2.7.11.25

XP_016858260.1

EC 2.7.11.25

XP_016858261.1

EC 2.7.11.25

NCBI Reference Sequences (RefSeq)

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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_051309.1 RefSeqGene

Range

6172..17859

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001297609.1 → NP_001284538.1 mitogen-activated protein kinase kinase kinase 6 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AB208805, AI658745, AW771625, FO393419

Consensus CDS

CCDS72738.1

UniProtKB/Swiss-Prot

O95382

Related

ENSP00000363152.2, OTTHUMP00000272468, ENST00000374040.7, OTTHUMT00000468165

Conserved Domains (3) summary

smart00220
Location:645 → 898

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06624
Location:631 → 898

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

pfam13281
Location:129 → 498

DUF4071; Domain of unknown function (DUF4071)
NM_004672.4 → NP_004663.3 mitogen-activated protein kinase kinase kinase 6 isoform 1

See identical proteins and their annotated locations for NP_004663.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AB167411, AF100318, AI658745, AW771625

Consensus CDS

CCDS299.1

UniProtKB/Swiss-Prot

O95382

Related

ENSP00000350195.2, OTTHUMP00000179079, ENST00000357582.2, OTTHUMT00000277002

Conserved Domains (3) summary

smart00220
Location:653 → 906

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06624
Location:639 → 906

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

pfam13281
Location:129 → 506

DUF4071; Domain of unknown function (DUF4071)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p12 Primary Assembly

Range

27355179..27368037 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017002771.1 → XP_016858260.1 mitogen-activated protein kinase kinase kinase 6 isoform X1
XM_017002772.1 → XP_016858261.1 mitogen-activated protein kinase kinase kinase 6 isoform X2