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MAP3K5 mitogen-activated protein kinase kinase kinase 5 [ Homo sapiens (human) ]

Gene ID: 4217, updated on 14-Jun-2020

Summary

Official Symbol
MAP3K5provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 5provided by HGNC
Primary source
HGNC:HGNC:6857
See related
Ensembl:ENSG00000197442 MIM:602448
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]
Expression
Broad expression in adrenal (RPKM 43.3), ovary (RPKM 21.3) and 23 other tissues See more
Orthologs

Genomic context

See MAP3K5 in Genome Data Viewer
Location:
6q23.3
Exon count:
32
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (136557046..136793098, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (136878184..137113656, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene microtubule associated protein 7 Neighboring gene NADH:ubiquinone oxidoreductase subunit S5 pseudogene 1 Neighboring gene RN7SK pseudogene 299 Neighboring gene MAP3K5 antisense RNA 1 Neighboring gene RNA, 5S ribosomal pseudogene 219 Neighboring gene uncharacterized LOC101928429 Neighboring gene Sharpr-MPRA regulatory region 14394 Neighboring gene peroxisomal biogenesis factor 7 Neighboring gene ribosomal protein L7a pseudogene 37 Neighboring gene solute carrier family 35 member D3

Genomic regions, transcripts, and products

Expression

  • 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Binding of HIV-1 gp120 to DC-SIGN leads to excessive ASK-1 activation and promotes ASK-1-dependent apoptosis in human dendritic cells PubMed
Nef nef HIV-1 Nef inhibits ASK1-induced phosphorylation of p54/p46 JNK in cells. Nef mutant (152DEVGEANN/AAAAAAAA159) abolishes its inhibitory activity PubMed
nef Mutations within the motif (152DEVGEANN159) of HIV-1 Nef impair its ability to interact with ASK1 and restore ASK1 anti-apoptosis function PubMed
nef Amino acids 152-159 in HIV-1 Nef and the N-terminal region (residues 1-318) and the C-terminal region (residues 905-1051) of ASK1 are involved in the binding between Nef and ASK1 PubMed
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 Nef inhibits ASK1/p38MAPK-dependent Mycobacterium tuberculosis-induced TNF-alpha production by inhibiting binding of ATF2 to the TNF-alpha promoter PubMed
nef HIV-1 Nef binds to ASK1 as demonstrated by GST-pull down and coimmunoprecipitation experiments PubMed
Vif vif ASK1 restricts the replication of HIV-1 by inhibiting Vif activity and promoting APOBEC3G incorporation into virions in CD4+ T-cells PubMed
vif ASK1 inhibits the interaction of HIV-1 Vif with ELOB/C in a dose-dependent manner, whereas no significant change is observed in the binding of Vif with CUL5 or CBFbeta PubMed
vif ASK1 markedly inhibits HIV-1 Vif-induced ubiquitination of APOBEC3G by a reduction in the Vif-ELOC interaction PubMed
vif The BC box (amino-acid residues 144-149) of HIV-1 Vif binds the C-terminal domain (amino-acid residues 955-1374) of ASK1 PubMed
vif ASK1 directly binds HIV-1 Vif and inhibits the anti-APOBEC3G activity by Vif PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

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 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase binding IEA
Inferred from Electronic Annotation
more info
 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
JNK cascade IDA
Inferred from Direct Assay
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
activation of MAPKK activity IDA
Inferred from Direct Assay
more info
PubMed 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cellular response to amino acid starvation IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to hydrogen peroxide IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to reactive nitrogen species IEA
Inferred from Electronic Annotation
more info
 
cellular response to stress IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to tumor necrosis factor IEA
Inferred from Electronic Annotation
more info
 
endothelial cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ISS
Inferred from Sequence or Structural Similarity
more info
 
intrinsic apoptotic signaling pathway in response to oxidative stress IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intrinsic apoptotic signaling pathway in response to oxidative stress IDA
Inferred from Direct Assay
more info
PubMed 
p38MAPK cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of JNK cascade ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of JUN kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cardiac muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of myoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of neuron death IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of neuron death ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of p38MAPK cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of vascular smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
programmed necrotic cell death IEA
Inferred from Electronic Annotation
more info
 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to ischemia IEA
Inferred from Electronic Annotation
more info
 
stress-activated MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
wound healing IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
IRE1-TRAF2-ASK1 complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
external side of plasma membrane IEA
Inferred from Electronic Annotation
more info
 
protein kinase complex IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IMP
Inferred from Mutant Phenotype
more info
PubMed 

General protein information

Preferred Names
mitogen-activated protein kinase kinase kinase 5
Names
ASK-1
MAP/ERK kinase kinase 5
MAPK/ERK kinase kinase 5
MEK kinase 5
MEKK 5
apoptosis signal-regulating kinase 1
NP_005914.1
XP_011534141.2
XP_016866359.1
XP_016866360.1
XP_016866361.1
XP_016866362.1
XP_016866363.1
XP_016866364.1
XP_016866365.1
XP_016866366.1

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

  1. NG_011965.1 RefSeqGene

    Range
    5042..240473
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005923.4NP_005914.1  mitogen-activated protein kinase kinase kinase 5

    See identical proteins and their annotated locations for NP_005914.1

    Status: REVIEWED

    Source sequence(s)
    AL024508, AL121933
    Consensus CDS
    CCDS5179.1
    UniProtKB/Swiss-Prot
    Q99683
    Related
    ENSP00000351908.4, ENST00000359015.5
    Conserved Domains (3) summary
    smart00220
    Location:685938
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd06624
    Location:671938
    STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
    pfam13281
    Location:165544
    DUF4071; Domain of unknown function (DUF4071)

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

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    136557046..136793098 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017010875.1XP_016866364.1  mitogen-activated protein kinase kinase kinase 5 isoform X6

  2. XM_017010872.1XP_016866361.1  mitogen-activated protein kinase kinase kinase 5 isoform X3

  3. XM_017010873.1XP_016866362.1  mitogen-activated protein kinase kinase kinase 5 isoform X4

  4. XM_017010877.1XP_016866366.1  mitogen-activated protein kinase kinase kinase 5 isoform X9

  5. XM_017010874.1XP_016866363.1  mitogen-activated protein kinase kinase kinase 5 isoform X5

  6. XM_017010871.1XP_016866360.1  mitogen-activated protein kinase kinase kinase 5 isoform X2

  7. XM_017010870.1XP_016866359.1  mitogen-activated protein kinase kinase kinase 5 isoform X1

  8. XM_017010876.1XP_016866365.1  mitogen-activated protein kinase kinase kinase 5 isoform X8

  9. XM_011535839.3XP_011534141.2  mitogen-activated protein kinase kinase kinase 5 isoform X7

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