DIABLO
Domain
The mature N-terminus mediates interaction with XIAP/BIRC4.
Function
Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/BRUCE by inhibiting its binding to caspases (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106).
Isoform 3
Attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation.
Isoform 1
Defective in the capacity to down-regulate the XIAP/BIRC4 abundance.
Involvement in disease
Deafness, autosomal dominant, 64
DFNA64
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated by BIRC7/livin (PubMed:16729033). Ubiquitinated by BIRC6 (PubMed:36758104, PubMed:36758105, PubMed:36758106).
The precursor form is proteolytically cleaved by mitochondrial processing peptidase MPP to remove the transit peptide and produce an intermediate form. This is then processed by PARL to produce the mature cleaved form which is released from mitochondria into the cytosol in apoptotic cells.
Sequence Similarities
Belongs to the Smac/DIABLO protein family.
Tissue Specificity
Ubiquitously expressed with highest expression in testis. Expression is also high in heart, liver, kidney, spleen, prostate and ovary. Low in brain, lung, thymus and peripheral blood leukocytes. Isoform 3 is ubiquitously expressed.
Cellular localization
- Mitochondrion
- Cytoplasm
- Cytosol
- Released into the cytosol in a PARL-dependent manner when cells undergo apoptosis.
Alternative names
SMAC, DIABLO, Diablo IAP-binding mitochondrial protein, Direct IAP-binding protein with low pI, Second mitochondria-derived activator of caspases