Induced myeloid leukemia cell differentiation protein Mcl-1

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.

Classification

Family (Pfam)

PF00452 Bcl-2

InterPro

Apop_reg_Mc1, Bcl-2-like_sf, Bcl-2_BH1-3, Bcl-2_fam, Bcl2-like, Bcl2_BH1_motif_CS, Bcl2_BH2_motif_CS, Bcl2_BH3_motif_CS

Functional cluster

Nucleic Acid Metabolism & Repair Enzymes

Experimental structures · PDB · 137

• 2KBW NMR
• 2MHS NMR
• 2NL9 X-ray 1.55A
• 2NLA X-ray 2.80A
• 2PQK X-ray 2.00A
• 3D7V X-ray 2.03A
• 3IO9 X-ray 2.40A
• 3KJ0 X-ray 1.70A
• 3KJ1 X-ray 1.94A
• 3KJ2 X-ray 2.35A
• 3KZ0 X-ray 2.35A
• 3MK8 X-ray 2.32A
• … and 125 more

A predicted model is available from AlphaFold.

Gene Ontology · 28

• GO:0097136 Bcl-2 family protein complex
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0016020 membrane
• GO:0005741 mitochondrial outer membrane
• GO:0005739 mitochondrion
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0051434 BH3 domain binding
• GO:0015267 channel activity
• GO:0046982 protein heterodimerization activity
• GO:0008320 protein transmembrane transporter activity
• GO:0001709 cell fate determination
• GO:0019725 cellular homeostasis
• GO:0006974 DNA damage response
• GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
• GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
• GO:0008053 mitochondrial fusion
• GO:2000811 negative regulation of anoikis
• GO:0043066 negative regulation of apoptotic process
• GO:0010507 negative regulation of autophagy
• GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• GO:0043065 positive regulation of apoptotic process
• GO:0043525 positive regulation of neuron apoptotic process
• GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
• GO:0042981 regulation of apoptotic process
• GO:0001836 release of cytochrome c from mitochondria
• GO:0034097 response to cytokine

Drugs targeting this protein · 1

• OBATOCLAX MESYLATE inhibitor

Related proteins · sequence + function similarity

• Induced myeloid leukemia cell differentiation protein Mcl-1 homolog 0.96
• Induced myeloid leukemia cell differentiation protein Mcl-1 homolog 0.95
• Induced myeloid leukemia cell differentiation protein Mcl-1 homolog 0.93
• Induced myeloid leukemia cell differentiation protein Mcl-1 homolog 0.93
• Anti-apoptotic protein NR13 0.65
• Anti-apoptotic protein NR13 0.64
• Apoptosis regulator R1 0.64
• Bcl-2-like protein 2 0.59
• Bcl-2-like protein 2 0.59
• Bcl-2-like protein 2 0.59
• Bcl-2-like protein 2 0.58
• Uncharacterized gene 1 protein 0.57

Co-cited proteins · studied together in the literature

• Induced myeloid leukemia cell differentiation protein Mcl-1 homolog 3 shared papers
• Ubiquitin carboxyl-terminal hydrolase 20 1 shared papers
• E3 ubiquitin-protein ligase HUWE1 1 shared papers
• Phorbol-12-myristate-13-acetate-induced protein 1 1 shared papers
• Phorbol-12-myristate-13-acetate-induced protein 1 1 shared papers
• Bcl-2-like protein 11 2 shared papers
• Mitogen-activated protein kinase 1 1 shared papers
• Bcl-2-like protein 11 2 shared papers
• Protein Bop 1 shared papers
• Glycogen synthase kinase-3 alpha 1 shared papers
• Ubiquitin carboxyl-terminal hydrolase 27 1 shared papers
• Bcl-2-like protein 1 1 shared papers

Literature · 25 cited papers

• The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein. Biochem. Biophys. Res. Commun. · 2022
• The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances apoptosis. EMBO Rep. · 2016
• Human Bop is a novel BH3-only member of the Bcl-2 protein family. Protein Cell · 2012
• Serine 162, an essential residue for the mitochondrial localization, stability and anti-apoptotic function of Mcl-1. PLoS ONE · 2012
• The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol. · 2010
• DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc. Natl. Acad. Sci. U.S.A. · 2007
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol. Cell · 2006
• Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 13 more in the literature graph