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induced myeloid leukemia cell differentiation protein Mcl-1; Bcl-2-related protein EAT/mcl1; mcl1/EAT; Bcl-2-like protein 3; Bcl2-L-3 (MCL1, BCL2L3)
Function:
- role in regulation of apoptosis versus cell survival, & in maintenance of viability but not of proliferation
- mediates its effects by interactions with other regulators of apoptosis
- isoform 1 inhibits apoptosis
- isoform 2 promotes apoptosis
- cleaved by CASP3 during apoptosis
- in intact cells, cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kD C-terminal fragment rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region
- phosphorylated on Thr-163
- treatment with taxol or okadaic acid induces phosphorylation on additional sites
- interacts with BAD, BOK, BIK & BFM (putative)
- interacts with PMAIP1
- isoform 1 interacts with BAX, BAK1, TPT1 & BCL2L11
- isoform 2 does not interact with pro-apoptotic BCL2-related proteins
Structure:
- belongs to the Bcl-2 family
- heterodimer of isoform 1 & isoform 2
- homodimers of isoform 1 or isoform 2 are not detected
Compartment:
- membrane, cytoplasm
- mitochondrion, nucleus, nucleoplasm
- cytoplasmic, associated with mitochondria
Alternative splicing: named isoforms=2
Expression:
- expression increases early during phorbol-ester induced differentiation along the monocyte/macrophage pathway in myeloid leukemia cell lines ML-1
- rapidly up-regulated by CSF2 in ML-1 cells
- up-regulated by heat-shock induced differentiation
- expression increases early during retinoic acid-induced differentiation
Note:
- isolated from ML-1 human myeloid leukemia cell line during phorbol ester induced differentiation
Interactions
molecular events
Related
mcl1 gene
General
bcl-2 subfamily protein
membrane protein
PEST protein
Properties
SIZE: entity length = 350 aa
MW = 37 kD
COMPARTMENT: mitochondria
cytoplasm
cell nucleus
MOTIF: PEST-like {104-175}
MOTIF: Ser phosphorylation site {S121}
proteolytic site {127-128}
proteolytic site {157-158}
Thr phosphorylation site {T163}
BH3 {209-223}
BH1 {252-272}
BH2 {304-319}
transmembrane domain {328-348}
Database Correlations
OMIM 159552
UniProt Q07820
Pfam PF00452
Entrez Gene 4170
Kegg hsa:4170
References
- Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW.
MCL1, a gene expressed in programmed myeloid cell
differentiation, has sequence similarity to BCL2.
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3516-20.
PMID: 7682708
- Yin XM, Oltvai ZN, Korsmeyer SJ.
BH1 and BH2 domains of Bcl-2 are required for inhibition of
apoptosis and heterodimerization with Bax.
Nature. 1994 May 26;369(6478):321-3.
PMID: 8183370