Diablo homolog

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Diablo, IAP-binding mitochondrial protein
Protein DIABLO PDB 1few.png
PDB rendering based on 1few.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM605219 MGI1913843 HomoloGene10532 GeneCards: DIABLO Gene
RNA expression pattern
PBB GE DIABLO 219350 s at tn.png
More reference expression data
Species Human Mouse
Entrez 56616 66593
Ensembl ENSG00000184047 ENSMUSG00000029433
UniProt Q9NR28 Q9JIQ3
RefSeq (mRNA) NM_001278302 NM_023232
RefSeq (protein) NP_001265231 NP_075721
Location (UCSC) Chr 12:
122.21 – 122.23 Mb
Chr 5:
123.51 – 123.53 Mb
PubMed search [1] [2]

Diablo homolog, is a mitochondrial protein that in humans is encoded by the DIABLO gene (direct IAP binding protein with low pI).[1][2][3] DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC.


SMAC is a mitochondrial protein that promotes cytochrome-c dependent activation by eliminating the effect of inhibitor of apoptosis protein (IAP) – a protein that negatively regulates apoptosis, programmed cell death.[4] SMAC is normally a mitochondrial protein, but it is found in the cytosol when a cell is primed for apoptosis during the final execution step of caspase activation. SMAC is the second protein in the apoptosis link, along with cytochrome c, that promotes apoptosis by activating caspases.

SMAC is an inhibitor of apoptosis protein (IAP)-binding protein. This mitochondrial protein enters the cytosol when cells undergo apoptosis, and it moderates the caspase inhibition of IAPs.


Multiple polyadenylation sites have been found for this gene. Several alternatively spliced transcript variants that encode distinct isoforms have been described for this gene but the validity of some transcripts, and their predicted ORFs, has not been determined conclusively.[3]


Diablo homolog has been shown to interact with:


  1. ^ McNeish IA, Bell S, McKay T, Tenev T, Marani M, Lemoine NR (May 2003). "Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway". Exp Cell Res 286 (2): 186–98. doi:10.1016/S0014-4827(03)00073-9. PMID 12749848. 
  2. ^ Yu J, Wang P, Ming L, Wood MA, Zhang L (June 2007). "SMAC/Diablo mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events". Oncogene 26 (29): 4189–98. doi:10.1038/sj.onc.1210196. PMID 17237824. 
  3. ^ a b "Entrez Gene: DIABLO diablo homolog (Drosophila)". 
  4. ^ Vucic D, Deshayes K, Ackerly H, Pisabarro MT, Kadkhodayan S, Fairbrother WJ et al. (April 2002). "SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP)". J. Biol. Chem. 277 (14): 12275–9. doi:10.1074/jbc.M112045200. PMID 11801603. 
  5. ^ a b Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE et al. (July 2000). "Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins". Cell 102 (1): 43–53. doi:10.1016/s0092-8674(00)00009-x. PMID 10929712. 
  6. ^ Hegde R, Srinivasula SM, Datta P, Madesh M, Wassell R, Zhang Z et al. (October 2003). "The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein". J. Biol. Chem. 278 (40): 38699–706. doi:10.1074/jbc.M303179200. PMID 12865429. 
  7. ^ a b Song Z, Yao X, Wu M (June 2003). "Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis". J. Biol. Chem. 278 (25): 23130–40. doi:10.1074/jbc.M300957200. PMID 12660240. 
  8. ^ Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin LL (April 2003). "Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis". J. Biol. Chem. 278 (16): 14363–9. doi:10.1074/jbc.M208672200. PMID 12571250. 
  9. ^ Hunter AM, Kottachchi D, Lewis J, Duckett CS, Korneluk RG, Liston P (February 2003). "A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO". J. Biol. Chem. 278 (9): 7494–9. doi:10.1074/jbc.C200695200. PMID 12511567. 
  10. ^ Davoodi J, Lin L, Kelly J, Liston P, MacKenzie AE (September 2004). "Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9". J. Biol. Chem. 279 (39): 40622–8. doi:10.1074/jbc.M405963200. PMID 15280366. 
  11. ^ Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM et al. (January 2002). "HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins". J. Biol. Chem. 277 (1): 445–54. doi:10.1074/jbc.M109891200. PMID 11604410. 

Further reading[edit]