Diablo homolog

Diablo, IAP-binding mitochondrial protein

PDB rendering based on 1few.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1FEW, 1G3F, 1G73, 1OXQ, 1TW6, 1XB0, 1XB1, 3D9U, 3UIH, 3UIJ

Identifiers

Symbols

DIABLO ; DFNA64; SMAC

External IDs

OMIM: 605219 MGI: 1913843 HomoloGene: 10532 GeneCards: DIABLO Gene

Gene ontology
Molecular function	• protein binding
Cellular component	• mitochondrion • mitochondrial intermembrane space • cytosol • cytoplasmic side of plasma membrane • CD40 receptor complex
Biological process	• apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • extrinsic apoptotic signaling pathway via death domain receptors • intrinsic apoptotic signaling pathway in response to oxidative stress • activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c • positive regulation of apoptotic process • neuron apoptotic process • intrinsic apoptotic signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
122.69 – 122.71 Mb

Chr 5:
123.51 – 123.52 Mb

PubMed search

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.

Function

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.

Gene

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]

Interactions

Diablo homolog has been shown to interact with:

BIRC2,^[5]^[6]
BIRC5,^[7]
LTBR,^[8] and
XIAP.^[5]^[7]^[9]^[10]^[11]

References

↑ 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.
↑ 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.
↑ 3.0 3.1 "Entrez Gene: DIABLO diablo homolog (Drosophila)".
↑ 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.
↑ 5.0 5.1 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.
↑ 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.
↑ 7.0 7.1 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Shi Y (2001). "A structural view of mitochondria-mediated apoptosis.". Nat. Struct. Biol. 8 (5): 394–401. doi:10.1038/87548. PMID 11323712.
Anguiano-Hernandez YM, Chartier A, Huerta S (2007). "Smac/DIABLO and colon cancer.". Anti-cancer agents in medicinal chemistry 7 (4): 467–73. doi:10.2174/187152007781058631. PMID 17630921.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Du C, Fang M, Li Y, Li L, Wang X (2000). "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition". Cell 102 (1): 33–42. doi:10.1016/S0092-8674(00)00008-8. PMID 10929711.
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE et al. (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.
Srinivasula SM, Datta P, Fan XJ, Fernandes-Alnemri T, Huang Z, Alnemri ES (2000). "Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway". J. Biol. Chem. 275 (46): 36152–7. doi:10.1074/jbc.C000533200. PMID 10950947.
Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y (2000). "Structural and biochemical basis of apoptotic activation by Smac/DIABLO". Nature 406 (6798): 855–62. doi:10.1038/35022514. PMID 10972280.
Liu Z, Sun C, Olejniczak ET, Meadows RP, Betz SF, Oost T et al. (2001). "Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain". Nature 408 (6815): 1004–8. doi:10.1038/35050006. PMID 11140637.
Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X et al. (2001). "Structural basis of IAP recognition by Smac/DIABLO". Nature 408 (6815): 1008–12. doi:10.1038/35050012. PMID 11140638.
Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J et al. (2001). "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature 410 (6824): 112–6. doi:10.1038/35065125. PMID 11242052.
Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001). "Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain". Cell 104 (5): 781–90. doi:10.1016/S0092-8674(01)00273-2. PMID 11257231.
Roberts DL, Merrison W, MacFarlane M, Cohen GM (2001). "The Inhibitor of Apoptosis Protein-Binding Domain of Smac Is Not Essential for Its Proapoptotic Activity". J. Cell Biol. 153 (1): 221–8. doi:10.1083/jcb.153.1.221. PMC 2185525. PMID 11285287.
Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM et al. (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.
Adrain C, Creagh EM, Martin SJ (2002). "Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2". EMBO J. 20 (23): 6627–36. doi:10.1093/emboj/20.23.6627. PMC 125329. PMID 11726499.
Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM (2002). "Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein". J. Biol. Chem. 277 (13): 11345–51. doi:10.1074/jbc.M109893200. PMID 11801595.

PDB gallery

1few: CRYSTAL STRUCTURE OF SMAC/DIABLO

1g73: CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN

Diablo homolog

Function

Gene

Interactions

References

Further reading