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diablo homolog, mitochondrial; second mitochondria-derived activator of caspase; smac protein; direct IAP-binding protein with low pI (DIABLO, SMAC)
Function:
- promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway
- released from mitochondria with cytochrome c during apoptosis
- associates with complex containing APAF
- acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP)
- interacts with NGFRAP1/BEX3 (putative)
- interacts with BIRC2, BIRC3, XIAP & BIRC7
Structure:
- homodimer
- the mature N-terminus mediates interaction with XIAP
Compartment:
- mitochondria
- released into the cytosol when cells undergo apoptosis
Alternative splicing: named isoforms=2
Expression:
- ubiquitously expressed with highest expression in testis
- expression is also high in heart, liver, kidney, spleen, prostate & ovary
- low expresion in brain, lung, thymus & peripheral blood leukocytes
Related
apoptotic protease-activating factor 1; APAF-1 (APAF1, KIAA0413)
Baculoviral IAP repeat-containing protein 4; E3 ubiquitin-protein ligase XIAP; inhibitor of apoptosis protein 3; X-linked inhibitor of apoptosis protein; X-linked IAP; IAP-like protein; HILP (XIAP, API3, BIRC4, IAP3)
General
mitochondrial protein
Properties
SIZE: entity length = 239 aa
MW = 27 kD
COMPARTMENT: mitochondria
cytoplasm
MOTIF: binding site
SITE: 56-60
FOR-BINDING-OF: inhibitor of apoptosis protein
References
- Du C, Fang M, Li Y, Li L, Wang X.
Smac, a mitochondrial protein that promotes cytochrome c-
dependent caspase activation by eliminating IAP inhibition.
Cell. 2000 Jul 7;102(1):33-42.
PMID: 10929711
- Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM,
Reid GE, Moritz RL, Simpson RJ, Vaux DL.
Identification of DIABLO, a mammalian protein that promotes
apoptosis by binding to and antagonizing IAP proteins.
Cell. 2000 Jul 7;102(1):43-53.
PMID: 10929712
- Adams JM, Cory S.
Life-or-death decisions by the Bcl-2 protein family.
Trends Biochem Sci. 2001 Jan;26(1):61-6. Review.
PMID: 11165519
- UniProt :accession Q9NR28
Databases & Figures
OMIM 605219
UniProt Q9NR28
Pfam PF09057
Entrez Gene 56616
Kegg hsa:56616
TRAIL -> caspase 8 -> bid -> smac/diablo -> IAP ...