Seeded MCL1 for the APOPTOSIS BCL2-family MOMP-control slice with
just fetch-gene human MCL1, yielding 117 GOA rows.
MCL1 is in PANTHER family PTHR11256, subfamily PTHR11256:SF46
("INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL-1"). The
human protein sits under the same broad PTN000135648 BCL2-family PAINT
node as BAX, BAK1, BCL2, and BCL2L1. That node carries both positive and
negative apoptotic regulation, channel activity, cytochrome-c release,
outer-membrane localization, DNA-damage intrinsic apoptosis, and
ligand-withdrawal signaling, so MCL1 inherited several rows that need
role/sign review rather than simple acceptance by family membership.
Canonical MCL-1L is a pro-survival OMM BCL2-family protein. Willis et al.
show that healthy cells keep BAK associated specifically with Mcl-1 and
Bcl-xL, and that displacement of BAK from both anti-apoptotic partners is
needed for BAK-mediated cell death PMID:15901672. Obatoclax experiments
then provide a membrane-preserving demonstration of the endogenous
MCL1/BAK complex: isolated intact mitochondria and intact SK-Mel5 cells
both showed obatoclax-sensitive MCL1/BAK association, while obatoclax
alone did not directly release cytochrome c from isolated mitochondria
PMID:18040043. These sources justify tightening broad generic
protein binding and apoptosis-regulation rows to BH3-domain binding
and negative regulation of MOMP or cytochrome-c release.
MCL1 has conditional pro-death products that must not be conflated with
the long isoform. Bae et al. describe MCL-1S as a short splice product
that lacks BH1/BH2 and the transmembrane domain, dimerizes with MCL-1L,
and induces apoptosis when overexpressed PMID:10837489. UniProt also
records caspase cleavage of intact MCL1 to a pro-apoptotic C-terminal
fragment. These findings explain old positive-apoptosis assertions but
do not turn canonical MCL-1L into a BAK/BAX-like pore.
Several rows are correctly secondary rather than core. MCL1 stability
falls after IL-3 withdrawal through GSK3-dependent S159
phosphorylation, ubiquitination, and degradation, and GSK3 inhibition
maintains MCL1, cytochrome-c retention, and survival in that
ligand-withdrawal context PMID:16543145. The BOK/MCL1 trophoblast
paper supports a BECN1-associated autophagy role in which pro-survival
MCL1 represses autophagy and BOK or oxidative stress disrupts that
state PMID:24113155. Cav1 stabilizes MCL1 and decreases
detachment-induced anoikis in lung carcinoma and melanoma cells, but the
reciprocal MCL1/Cav1 protein-binding row is still a low-information
generic contact for MCL1 itself PMID:22277751.
The GOA file has many GO:0005515 protein binding imports from large
IntAct or screening papers. Focused BCL2-family interaction sources can
be converted to GO:0051434 BH3 domain binding; large interactome rows
or enzyme/substrate contacts to USP9X, HUWE1, AKT1, and membrane traffic
proteins should not be retained as generic MCL1 molecular functions.
The annotation-reviewer audit agreed with the central BH3-groove/MOMP
framing and the sign fixes, but identified several abstract-only rows
where the initial pass was too confident. Those BIM/BID/PUMA/NOXA/BAX
rows were changed back to UNDECIDED pending the hidden full text, the
Reactome expression-module cytosol rows were removed, mitochondrial
fusion and cytokine-withdrawal apoptosis were kept as non-core
contexts, and the stability-control paragraph was folded out of
core_functions so the only core activity is canonical MCL-1L
BH3-domain binding at the OMM.