MCL1 MCL1 apoptosis regulator, BCL2 family member [Homo sapiens (human)] - Gene

Summary

Official Symbol: MCL1provided by HGNC
Official Full Name: MCL1 apoptosis regulator, BCL2 family memberprovided by HGNC
Primary source: HGNC:HGNC:6943
See related: Ensembl:ENSG00000143384 MIM:159552; AllianceGenome:HGNC:6943
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: TM; EAT; MCL1L; MCL1S; Mcl-1; BCL2L3; MCL1-ES; bcl2-L-3; mcl1/EAT
Summary: This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]
Expression: Ubiquitous expression in bone marrow (RPKM 341.7), gall bladder (RPKM 276.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (150574558..150579610, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (149698578..149703635, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (150547034..150552086, 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

RVFV virulence factor NSs triggers the mitochondrial MCL-1-BAK axis to activate pathogenic NLRP3 pyroptosis.
Title: RVFV virulence factor NSs triggers the mitochondrial MCL-1-BAK axis to activate pathogenic NLRP3 pyroptosis.
TCEB3 initiates ovarian cancer apoptosis by mediating ubiquitination and degradation of MCL-1.
Title: TCEB3 initiates ovarian cancer apoptosis by mediating ubiquitination and degradation of MCL-1.
Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.
Title: Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.
Mcl-1 Protein and Viral Infections: A Narrative Review.
Title: Mcl-1 Protein and Viral Infections: A Narrative Review.
FBXW7 affects autophagy through MCL1 in oral squamous cell carcinoma.
Title: FBXW7 affects autophagy through MCL1 in oral squamous cell carcinoma.
Myeloid cell leukemia-1 as a candidate prognostic biomarker in cancers: a systematic review and meta-analysis.
Title: Myeloid cell leukemia-1 as a candidate prognostic biomarker in cancers: a systematic review and meta-analysis.
MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs' patients.
Title: MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs' patients.
Polypyrimidine tract binding protein 1 (PTBP1) contains a novel regulatory sequence, the rBH3, that binds the prosurvival protein MCL1.
Title: Polypyrimidine tract binding protein 1 (PTBP1) contains a novel regulatory sequence, the rBH3, that binds the prosurvival protein MCL1.
SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.
Title: SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.
Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.
Title: Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.

Submit: New GeneRIF Correction See all GeneRIFs (674)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies genetic risk underlying primary rhegmatogenous retinal detachment. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Gp120-induced M-CSF downregulates the TRAIL receptor TRAIL-R1/DR4 and upregulates the anti-apoptotic genes Bfl-1 and Mcl-1	PubMed
Vpr	vpr	Bcl-xL and MCL-1 play a critical role in macrophage survival but not in resistance to HIV-1 Vpr-induced apoptosis	PubMed
retropepsin	gag-pol	HIV-1 PR is identified to have a physical interaction with myeloid cell leukemia sequence 1 (BCL2-related) (MCL1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-34987 (e-PCR)
- UniSTS:5380

RH78781 (e-PCR)
- UniSTS:50776

PMC152246P2 (e-PCR)
- UniSTS:271204

SHGC-2474 (e-PCR)
- UniSTS:39796

WI-20019 (e-PCR)
- UniSTS:47749

RH68997 (e-PCR)
- UniSTS:50598

RH67950 (e-PCR)
- UniSTS:88241

D1S3568 (e-PCR)
- UniSTS:60888

MCL1_369 (e-PCR)
- UniSTS:277483

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables BH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell fate determination	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in extrinsic apoptotic signaling pathway in absence of ligand	IBA Inferred from Biological aspect of Ancestor more info
involved_in extrinsic apoptotic signaling pathway in absence of ligand	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial fusion	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of anoikis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in release of cytochrome c from mitochondria	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within response to cytokine	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of Bcl-2 family protein complex	IDA Inferred from Direct Assay more info	PubMed
part_of Bcl-2 family protein complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in mitochondrial outer membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial outer membrane	TAS Traceable Author Statement more info	PubMed
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: induced myeloid leukemia cell differentiation protein Mcl-1

Names: BCL2 family apoptosis regulator; MCL1, BCL2 family apoptosis regulator; bcl-2-like protein 3; bcl-2-related protein EAT/mcl1; myeloid cell leukemia 1; myeloid cell leukemia ES; myeloid cell leukemia sequence 1 (BCL2-related)

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_029146.2 RefSeqGene

Range

5000..10052

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001197320.2 → NP_001184249.1 induced myeloid leukemia cell differentiation protein Mcl-1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as MCL-1ES (extra short), uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AL356356

Consensus CDS

CCDS72909.1

UniProtKB/TrEMBL

A0A087WT64, C8YZ26

Related

ENSP00000477624.1, ENST00000620947.4

Conserved Domains (1) summary

cd06845
Location:49 → 165

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...
NM_021960.5 → NP_068779.1 induced myeloid leukemia cell differentiation protein Mcl-1 isoform 1

See identical proteins and their annotated locations for NP_068779.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as MCL-1L (long), represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL356356

Consensus CDS

CCDS957.1

UniProtKB/Swiss-Prot

B2R6B2, D3DV03, D3DV04, Q07820, Q9HD91, Q9NRQ3, Q9NRQ4, Q9UHR7, Q9UHR8, Q9UHR9, Q9UNJ1

Related

ENSP00000358022.2, ENST00000369026.3

Conserved Domains (1) summary

cd06845
Location:175 → 318

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...
NM_182763.3 → NP_877495.1 induced myeloid leukemia cell differentiation protein Mcl-1 isoform 2

See identical proteins and their annotated locations for NP_877495.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as MCL-1S (short), lacks an alternate exon that causes a frameshift, compared to variant 1. The resulting protein (isoform 2) has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL356356

Consensus CDS

CCDS956.1

UniProtKB/Swiss-Prot

Q07820

Related

ENSP00000309973.3, ENST00000307940.3

Conserved Domains (1) summary

cl02575
Location:175 → 230

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...