BIRC6
Domain
The BIR domain is essential for its anti-apoptotic function and is important for binding to DIABLO/SMAC and caspases.
Function
Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369).
Post-translational modifications
Ubiquitinated; mediated by RNF41 E3 ligase and leads to proteasomal degradation, impairing inhibition of apoptosis (PubMed:14765125). Deubiquitinated by USP8/UBPY (PubMed:18329369). Autoubiquitinated; mediated by E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106).
Proteolytically cleaved. Acts as substrate for CASP3, CASP6, CASP7, CASP9 and HTRA2.
Sequence Similarities
Belongs to the BIRC6 family.
Tissue Specificity
Expressed in brain cancer cells.
Cellular localization
- Golgi apparatus
- trans-Golgi network membrane
- Endosome
- Cytoplasm
- Cytoskeleton
- Spindle pole
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Midbody
- Midbody ring
- Exhibits cell cycle-dependent localization. Concentrates in a pericentriolar compartment in interphase, moves partially to spindle poles in metaphase, and finally localizes to the spindle midzone and the midbody in telophase and during cytokinesis. On the midbody, localizes to the midbody ring, also called Flemming body (PubMed:18329369). In interphase cells, localizes to the trans-Golgi network membrane and endosomes. During cytokinesis, a fraction moves to the midzone where it specifically arrives at the midbody ring. After abscission completion, travels with the midbody remnant into one daughter cell, and remains bound to it until a new midbody ring is formed during the next cell division (PubMed:18329369).
Alternative names
KIAA1289, BIRC6, Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6, BIR repeat-containing ubiquitin-conjugating enzyme, Baculoviral IAP repeat-containing protein 6, Ubiquitin-conjugating BIR domain enzyme apollon, BRUCE, APOLLON