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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

  1. 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
  2. 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
  3. 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
  4. UniProt :accession Q9NR28

Databases & Figures

OMIM 605219 UniProt Q9NR28 Pfam PF09057 Entrez Gene 56616 Kegg hsa:56616 TRAIL -> caspase 8 -> bid -> smac/diablo -> IAP ...