MCL1 myeloid cell leukemia sequence 1 (BCL2-related) [Homo sapiens] - Gene

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Summary

Official Symbol: MCL1provided by HGNC
Official Full Name: myeloid cell leukemia sequence 1 (BCL2-related)provided by HGNC
Primary source: HGNC:6943
See related: Ensembl:ENSG00000143384; HPRD:08870; MIM:159552; Vega:OTTHUMG00000034867
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; MGC1839; MGC104264
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]

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Genomic context

Location :: 1q21

Sequence :: Chromosome: 1; NC_000001.10 (150547027..150552214, complement)

See MCL1 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Depletion of Mcl-1 sensitized tumor cells to MEK inhibitor-induced cell death, an effect that was antagonized by knockdown of Bim.
Title: Up-regulation of pro-apoptotic protein Bim and down-regulation of anti-apoptotic protein Mcl-1 cooperatively mediate enhanced tumor cell death induced by the combination of ERK kinase (MEK) inhibitor and microtubule inhibitor.
maritoclax represents a new class of Mcl-1 inhibitors, which antagonizes Mcl-1 and overcomes ABT-737 resistance by targeting Mcl-1 for degradation.
Title: Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation.
common variants in MCL1 promoter correlated with increased transactivation in solid cancer cells and were associated with reduced risk of lung cancer in nonsmokers.
Title: Functional regulatory variants of MCL1 contribute to enhanced promoter activity and reduced risk of lung cancer in nonsmokers: implications for context-dependent phenotype of an antiapoptotic and antiproliferative gene in solid tumor.
These findings suggested the dysregulation of the apoptosis-related proteins MCL1 and BAK1 in multiple sclerosis.
Title: Aberrant expression of the apoptosis-related proteins BAK and MCL1 in T cells in multiple sclerosis.
short-lived prosurvival Bcl-2 family protein, Mcl-1 (myeloid cell leukemia-1), is instrumental in controlling apoptosis and consequently neutrophil lifespan in response to rapidly changing environmental cues during inflammation
Title: Regulation of neutrophil survival/apoptosis by Mcl-1.
MCL-1 regulates the balance between autophagy and apoptosis.
Title: MCL-1 regulates the balance between autophagy and apoptosis.
The apoptosis process in human neutrophils exposed to NDMA is dependent on the intrinsic pathway mediated by Bax and Mcl-1 proteins.
Title: The effect of N-nitrosodimethylamine (NDMA) on Bax and Mcl-1 expression in human neutrophils.
Mcl-1 is critical for survival of human AML cells
Title: Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia.
Upregulation of myeloid cell leukemia protein-1 by human cytomegalovirus transiently protects nonpermissive myeloid cells from chemical and virus entry-induced cell death.
Title: Human cytomegalovirus activation of ERK and myeloid cell leukemia-1 protein correlates with survival of latently infected cells.
High Mcl-1 is associated with glioblastoma.
Title: ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.

Submit: New GeneRIF Correction See all (227)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_877495.1		IER3	BIND	PubMed	An unspecified isoform of IEX-1 interacts with MCL1.
Q07820	Q92934	BAD	HPRD	PubMed
Q07820	Q16611	BAK1	HPRD	PubMed
Q07820	Q07814	BAX	HPRD	PubMed
Q07820	Q9BXH1	BBC3	HPRD	PubMed
Q07820	Q07817	BCL2L1	HPRD	PubMed
Q07820	O43521	BCL2L11	HPRD	PubMed
Q07820	P55957	BID	HPRD	PubMed
Q07820	Q13323	BIK	HPRD	PubMed
Q07820	Q96LC9	BMF	HPRD	PubMed
Q07820	Q9UMX3	BOK	HPRD	PubMed
Q07820	P42574	CASP3	HPRD	PubMed
Q07820	P61803	DAD1	HPRD	PubMed
Q07820	P49840	GSK3A	HPRD	PubMed
Q07820	P49841	GSK3B	HPRD	PubMed
Q07820	Q7Z6Z7	HUWE1	HPRD	PubMed
Q07820	P28482	MAPK1	HPRD	PubMed
Q07820	Q07820	MCL1	HPRD	PubMed
Q07820	P12004	PCNA	HPRD	PubMed
Q07820	Q13794	PMAIP1	HPRD	PubMed
Q07820	O95271	TNKS	HPRD	PubMed
Q07820	P13693	TPT1	HPRD	PubMed
Q07820	P21796	VDAC1	HPRD	PubMed
BioGRID:110338	BioGRID:107048	BAD	BioGRID	PubMed	Protein-peptide; Reconstituted Complex; Two-hybrid
BioGRID:110338	BioGRID:107054	BAK1	BioGRID	PubMed	Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid
BioGRID:110338	BioGRID:107057	BAX	BioGRID	PubMed	Two-hybrid
	NP_055232.1	BBC3	BIND	PubMed	Mcl-1 interacts with Puma. This interaction was modelled on a demonstrated interaction between Mcl-1 from an unspecified species and human Puma.
BioGRID:110338	BioGRID:118009	BBC3	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110338	BioGRID:107070	BCL2L1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110338	BioGRID:115335	BCL2L11	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110338	BioGRID:107106	BID	BioGRID	PubMed	Affinity Capture-Western; Protein-peptide; Reconstituted Complex
BioGRID:110338	BioGRID:107107	BIK	BioGRID	PubMed	Protein-peptide; Reconstituted Complex
	NP_001003940.1	BMF	BIND	PubMed	Mcl-1 interacts with Bmf. This interaction was modelled on a demonstrated interaction between Mcl-1 from an unspecified species and human Bmf.
BioGRID:110338	BioGRID:124716	BMF	BioGRID	PubMed	Protein-peptide
BioGRID:110338	BioGRID:107134	BOK	BioGRID	PubMed	Two-hybrid
BioGRID:110338	BioGRID:198352	Bcl2l11	BioGRID	PubMed	Protein-peptide; Two-hybrid
BioGRID:110338	BioGRID:107286	CASP3	BioGRID	PubMed	Biochemical Activity
BioGRID:110338	BioGRID:107973	DAD1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110338	BioGRID:114276	HRK	BioGRID	PubMed	Protein-peptide
	NP_113584.3	HUWE1	BIND	PubMed	Mule interacts with and ubiquitinates Mcl-1.
BioGRID:110338	BioGRID:115385	HUWE1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:110338	BioGRID:111588	MAPK10	BioGRID	PubMed	Biochemical Activity
BioGRID:110338	BioGRID:110338	MCL1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110338	BioGRID:111142	PCNA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110338	BioGRID:111317	PIN1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110338	BioGRID:111379	PMAIP1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110338	BioGRID:114207	TNKS	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110338	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110338	BioGRID:125434	UHRF2	BioGRID	PubMed	Far Western
BioGRID:110338	BioGRID:113867	USP9X	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:110338	BioGRID:113259	VDAC1	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
BH3 domain binding	IPI Inferred from Physical Interaction more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein channel activity	TAS Traceable Author Statement more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
anti-apoptosis	TAS Traceable Author Statement more info	PubMed
apoptotic process	IDA Inferred from Direct Assay more info	PubMed
cell differentiation	IEA Inferred from Electronic Annotation more info
cell fate determination	NAS Non-traceable Author Statement more info	PubMed
cellular homeostasis	NAS Non-traceable Author Statement more info	PubMed
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IMP Inferred from Mutant Phenotype more info
response to cytokine stimulus	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
Bcl-2 family protein complex	IDA Inferred from Direct Assay more info
cytoplasm	TAS Traceable Author Statement more info	PubMed
integral to membrane	IEA Inferred from Electronic Annotation more info
membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrial matrix	IEA Inferred from Electronic Annotation more info
mitochondrial outer membrane	TAS Traceable Author Statement more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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

Names: induced myeloid leukemia cell differentiation protein Mcl-1; bcl-2-like protein 3; myeloid cell leukemia ES; bcl-2-related protein EAT/mcl1

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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

NG_029146.1 RefSeqGene

Range

5001..10192

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001197320.1 → 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)

AK312508, AL356356, BC017197, CA421486, FJ917536

UniProtKB/TrEMBL

C8YZ26

UniProtKB/Swiss-Prot

Q07820

Conserved Domains (1) summary

cd06845
Location:49 – 165
Blast Score: 341

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_021960.4 → NP_068779.1 induced myeloid leukemia cell differentiation protein Mcl-1 isoform 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)

AK312508, AL356356, BC017197, CA421486

Consensus CDS

CCDS957.1

UniProtKB/Swiss-Prot

Q07820

Related

ENSP00000358022, OTTHUMP00000032794, ENST00000369026, OTTHUMT00000084402

Conserved Domains (1) summary

cd06845
Location:175 – 318
Blast Score: 381

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_182763.2 → NP_877495.1 induced myeloid leukemia cell differentiation protein Mcl-1 isoform 2

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)

AF203373, AK312508, AL356356, BC017197, CA421486

Consensus CDS

CCDS956.1

UniProtKB/Swiss-Prot

Q07820

Related

ENSP00000309973, OTTHUMP00000032795, ENST00000307940, OTTHUMT00000084403

Conserved Domains (1) summary

cl02575
Location:175 – 230
Blast Score: 100

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 ...

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p5 Primary Assembly

Range

150547027..150552214, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

121925157..121930349, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF147742.1	AAF74821.1
genomic	AF162677.1	AAG00896.1
genomic	AF198614.1	AAF64255.1
		AAF64256.1
genomic	AL356356.17	CAI15503.1
		CAI15504.1
genomic	CH471121.2	EAW53538.1
		EAW53539.1
		EAW53540.1
		EAW53541.1
genomic	DQ088966.1	AAY68220.1
mRNA	AA453505.1	None
mRNA	AF118124.1	AAD13299.1
mRNA	AF118276.1	AAF15309.1
mRNA	AF118277.1	AAF15310.1
mRNA	AF118278.1	AAF15311.1
mRNA	AF203373.1	AAG00904.1
mRNA	AK294462.1	BAG57694.1
mRNA	AK297217.1	BAG59700.1
mRNA	AK300499.1	BAG62213.1
mRNA	AK304775.1	BAG65530.1
mRNA	AK312508.1	BAG35409.1
mRNA	AK316267.1	BAH14638.1
mRNA	BC017197.2	AAH17197.1
mRNA	BC071897.1	AAH71897.1
mRNA	BC107735.1	AAI07736.1
mRNA	BT006640.1	AAP35286.1
mRNA	CA421486.1	None
mRNA	FJ917536.1	ACV83304.1
mRNA	L08246.1	None
other-genetic	DQ890628.2	ABM92245.1
other-genetic	DQ893795.2	ABM84721.1