Browse MAP3K5

Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region.
Domain PF13281 Domain of unknown function (DUF4071)
PF00069 Protein kinase domain
Function

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).

> Gene Ontology
 
Biological Process GO:0000186 activation of MAPKK activity
GO:0000187 activation of MAPK activity
GO:0000302 response to reactive oxygen species
GO:0002931 response to ischemia
GO:0006979 response to oxidative stress
GO:0007254 JNK cascade
GO:0007257 activation of JUN kinase activity
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0010035 response to inorganic substance
GO:0010657 muscle cell apoptotic process
GO:0010658 striated muscle cell apoptotic process
GO:0010659 cardiac muscle cell apoptotic process
GO:0010660 regulation of muscle cell apoptotic process
GO:0010661 positive regulation of muscle cell apoptotic process
GO:0010662 regulation of striated muscle cell apoptotic process
GO:0010663 positive regulation of striated muscle cell apoptotic process
GO:0010665 regulation of cardiac muscle cell apoptotic process
GO:0010666 positive regulation of cardiac muscle cell apoptotic process
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032147 activation of protein kinase activity
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033002 muscle cell proliferation
GO:0033674 positive regulation of kinase activity
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0034614 cellular response to reactive oxygen species
GO:0034976 response to endoplasmic reticulum stress
GO:0036473 cell death in response to oxidative stress
GO:0038066 p38MAPK cascade
GO:0042542 response to hydrogen peroxide
GO:0042692 muscle cell differentiation
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043506 regulation of JUN kinase activity
GO:0043507 positive regulation of JUN kinase activity
GO:0045445 myoblast differentiation
GO:0045661 regulation of myoblast differentiation
GO:0045663 positive regulation of myoblast differentiation
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051147 regulation of muscle cell differentiation
GO:0051149 positive regulation of muscle cell differentiation
GO:0051403 stress-activated MAPK cascade
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070265 necrotic cell death
GO:0070301 cellular response to hydrogen peroxide
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070997 neuron death
GO:0071356 cellular response to tumor necrosis factor
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072577 endothelial cell apoptotic process
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097300 programmed necrotic cell death
GO:1900744 regulation of p38MAPK cascade
GO:1900745 positive regulation of p38MAPK cascade
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1902170 cellular response to reactive nitrogen species
GO:1904019 epithelial cell apoptotic process
GO:1904705 regulation of vascular smooth muscle cell proliferation
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1990874 vascular smooth muscle cell proliferation
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
Molecular Function GO:0000287 magnesium ion binding
GO:0004674 protein serine/threonine kinase activity
GO:0004702 receptor signaling protein serine/threonine kinase activity
GO:0004709 MAP kinase kinase kinase activity
GO:0005057 receptor signaling protein activity
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:0098552 side of membrane
GO:1902911 protein kinase complex
GO:1990604 IRE1-TRAF2-ASK1 complex
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04210 Apoptosis
hsa04530 Tight junction
hsa04668 TNF signaling pathway
hsa04722 Neurotrophin signaling pathway
Reactome R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-2559580: Oxidative Stress Induced Senescence
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MAP3K5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of MAP3K5 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.58 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of MAP3K5 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.170.584
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1460.886
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1820.796
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0250.927
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0150.995
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0740.979
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2480.588
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7270.59
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2890.848
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9920.31
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.5370.299
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3520.000468
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MAP3K5 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.82.712.10.0439
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.83.411.40.0746
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)2117195.913.10.355
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131123.19.1140.596
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP3K5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP3K5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP3K5.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP3K5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MAP3K5 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MAP3K5 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMAP3K5
Namemitogen-activated protein kinase kinase kinase 5
Aliases MAPKKK5; ASK1; apoptosis signal regulating kinase 1; MEKK5; ASK-1; MAP/ERK kinase kinase 5; MAPK/ERK kinase ......
Chromosomal Location6q22.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MAP3K5 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.