Browse MCL1

Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
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 Membrane Single-pass membrane protein Cytoplasm. Mitochondrion. Nucleus, nucleoplasm. Note=Cytoplasmic, associated with mitochondria.
Domain PF00452 Apoptosis regulator proteins
Function

Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.

> Gene Ontology
 
Biological Process GO:0001709 cell fate determination
GO:0006914 autophagy
GO:0006979 response to oxidative stress
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0008637 apoptotic mitochondrial changes
GO:0010506 regulation of autophagy
GO:0010507 negative regulation of autophagy
GO:0034599 cellular response to oxidative stress
GO:0036473 cell death in response to oxidative stress
GO:0036475 neuron death in response to oxidative stress
GO:0036480 neuron intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0038034 signal transduction in absence of ligand
GO:0043276 anoikis
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0045165 cell fate commitment
GO:0051402 neuron apoptotic process
GO:0070997 neuron death
GO:0071806 protein transmembrane transport
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097193 intrinsic apoptotic signaling pathway
GO:1900407 regulation of cellular response to oxidative stress
GO:1900409 positive regulation of cellular response to oxidative stress
GO:1901099 negative regulation of signal transduction in absence of ligand
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1902175 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902177 positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902532 negative regulation of intracellular signal transduction
GO:1902882 regulation of response to oxidative stress
GO:1902884 positive regulation of response to oxidative stress
GO:1903201 regulation of oxidative stress-induced cell death
GO:1903203 regulation of oxidative stress-induced neuron death
GO:1903209 positive regulation of oxidative stress-induced cell death
GO:1903223 positive regulation of oxidative stress-induced neuron death
GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:2000209 regulation of anoikis
GO:2000811 negative regulation of anoikis
GO:2001020 regulation of response to DNA damage stimulus
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0008320 protein transmembrane transporter activity
GO:0008565 protein transporter activity
GO:0015266 protein channel activity
GO:0015267 channel activity
GO:0022803 passive transmembrane transporter activity
GO:0022884 macromolecule transmembrane transporter activity
GO:0046982 protein heterodimerization activity
GO:0051400 BH domain binding
GO:0051434 BH3 domain binding
GO:0070513 death domain binding
Cellular Component GO:0005741 mitochondrial outer membrane
GO:0005759 mitochondrial matrix
GO:0019867 outer membrane
GO:0031968 organelle outer membrane
GO:0097136 Bcl-2 family protein complex
> KEGG and Reactome Pathway
 
KEGG hsa04151 PI3K-Akt signaling pathway
hsa04210 Apoptosis
hsa04630 Jak-STAT signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-449147: Signaling by Interleukins
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MCL1 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
 
  Literatures describing the relation between MCL1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29408314CholangiocarcinomaInhibit immunityEnforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture.
21712448Melanoma; Breast Carcinoma; Floor of Mouth Squamous Cell CarcinomaInhibit immunityWe further showed a key role for Mcl-1 in that its knockdown or inhibition abrogated the effects of IL-7. In addition, knockdown of the Mcl-1 binding partner and proapoptotic protein Bim protected T cells from these dysfunctional alterations.
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
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 MCL1 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 logFC: -2.48; FDR: 0.03410 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
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
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
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 MCL1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1760.489
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2530.936
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1160.959
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0940.831
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1530.957
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3960.918
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0370.946
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.2040.931
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3030.909
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8030.703
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1920.712
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0330.709
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MCL1 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) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
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
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MCL1. 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
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MCL1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MCL1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MCL1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MCL1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MCL1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMCL1
Namemyeloid cell leukemia 1
Aliases BCL2L3; Mcl-1; myeloid cell leukemia sequence 1 (BCL2-related); EAT-ES; MCL1L; MCL1S; bcl2-L-3; mcl1/EAT; bc ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MCL1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MCL1.
ID Name Drug Type Targets #Targets
DB09401IsosorbideSmall MoleculeBCL2, BCL2L1, MCL13