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FLASH GENE
Symbol DIABLO contributors: mct/ - updated : 04-06-2014
HGNC name diablo homolog (Drosophila)
HGNC id 21528
Corresponding disease
DFNA64 neurosensory deafness 64, dominant
Location 12q24.31      Physical location : 122.692.209 - 122.712.068
Synonym name
  • direct IAP-binding protein with low pI
  • second mitochondria-derived activator of caspase
  • mitochondrial smac protein
  • Synonym symbol(s) SMAC, SMAC3, DIABLO-S, FLJ10537, FLJ25049, 0610041G12Rik, DFNA64
    DNA
    TYPE functioning gene
    STRUCTURE 19.86 kb     6 Exon(s)
    regulatory sequence Binding site   transcription factor
    text structure E2F1-binding sites BS2 (-542 approximately -535 bp) and BS3 (-200 approximately -193 bp)
    MAPPING cloned Y linked N status provisional
    Map cen - D12S1349 - DIABLO - D12S1578 - D12S1158E - qter
    Physical map
    LOC390363 12 similar to 60S ribosomal protein L12 FLJ38690 12q24.31 hypothetical protein FLJ38690 TCF1 12q24.2 transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1), albumin proximal factor FLJ12448 12q hypothetical protein FLJ12448 OASL 12q24.2 2'-5'-oligoadenylate synthetase-like LOC390364 12 similar to 60S ribosomal protein L10 (QM protein homolog) P2RX7 12q24.2-q24.31 purinergic receptor P2X, ligand-gated ion channel, 7 P2RX4 12q24.32 purinergic receptor P2X, ligand-gated ion channel, 4 CAMKK2 12q24.32-q24.33 calcium/calmodulin-dependent protein kinase kinase 2, beta ANAPC5 12q24.2-q24.32 anaphase promoting complex subunit 5 RNF34 12q24.31 ring finger protein 34 FBXL10 12q24.31 F-box and leucine-rich repeat protein 10 FLJ14466 12q24.31 hypothetical protein FLJ14466 LOC283385 12q24.31 morn LOC144404 12q24.31 similar to transmembrane protein induced by tumor necrosis factor alpha ARHF 12q24.31 ras homolog gene family, member F (in filopodia) LOC338799 12q24.31 hypothetical protein LOC338799 KIAA1076 12q24.31 KIAA1076 protein HPD 12q24.1-q24.32 4-hydroxyphenylpyruvate dioxygenase PSMD9 12q24.31-q24.32 proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 MGC33630 12q24.31 hypothetical protein MGC33630 BCL7A 12q24.13 B-cell CLL/lymphoma 7A MONDOA 12q21.31 Mlx interactor MGC35140 12q24.31 hypothetical protein MGC35140 B3GNT4 12q24 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4 DIABLO 12q24.1-q24.31 diablo homolog (Drosophila) VPS33A 12q24.31 vacuolar protein sorting 33A (yeast) RSN 12q24.3 restin (Reed-Steinberg cell-expressed intermediate filament-associated protein) RPL21P1 12q24.2-q24.3 ribosomal protein L21 pseudogene 1 DKFZp434E2220 12q24.31 hypothetical protein DKFZp434E2220 FLJ11021 12q24.31 similar to splicing factor, arginine/serine-rich 4 KNTC1 12q24.31 kinetochore associated 1 HM74a 12q24.31 G protein-coupled receptor HM74a HM74 12q24.31 G protein-coupled receptor HM74a GPR81 12q24.3 G protein-coupled receptor 81 DENR 12q24.31 density-regulated protein TSP-NY 12q24.31 testis-specific protein TSP-NY HIP1R 12q24 huntingtin interacting protein-1-related FLJ12750 12q24.31 hypothetical protein FLJ12750 ABCB9 12q24.31-q24.32 ATP-binding cassette, sub-family B (MDR/TAP), member 9 FLJ13491 12q24.31 hypothetical protein FLJ13491 ARL6IP4 12q24.31 ADP-ribosylation-like factor 6 interacting protein 4 PITPNM2 12q24.31 phosphatidylinositol transfer protein, membrane-associated 2 FLJ13769 12q24.31 hypothetical protein FLJ13769 MPHOSPH9 12q24.31 M-phase phosphoprotein 9 FLJ38663 12q24.31 hypothetical protein FLJ38663 CDK2AP1 12q24.31 CDK2-associated protein 1 SBNO1 12q24.31 sno, strawberry notch homolog 1 (Drosophila) LOC387893 12 similar to SET domain-containing protein 8 MGC7036 12q24.31 hypothetical protein MGC7036 RNP24 12q24.31 coated vesicle membrane protein DDX55 12q24.31 DEAD (Asp-Glu-Ala-Asp) box polypeptide 55
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2265 27.1 239 - 2007 17440818
    isoform Smac-alpha
    6 - 2133 - 195 - 2007 17440818
  • lacking an in-frame segment compared to variant 1
  • isoform 3 is shorter than isoform 1 and retains only a small portion of the IAP-binding domain
  • isoform known as Smac-delta
  • - - 1985 - 186 - 2007 17440818
  • Smac-beta and Smac/DIABLO-S
  • - - 1882 - 195 - 2007 17440818
    - - 2483 - 186 - 2007 17440818
  • DIABLO-S
  • - - 1881 - 166 - 2007 17440818
    - - 1853 - 142 - 2007 17440818
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Lymphoid/Immunespleen    
    Reproductivefemale systemovary  highly
     male systemtestis  highly
     male systemprostate  highly
    Urinarykidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    mono polymer homomer , dimer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Diablo (85.2pc)
    homolog to rattus Diablo (85.7pc)
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    text released from mitochondria at entering the cytosol during apoptosis triggered by UV or gamma irradiation, cytotoxic drugs and DNA damage
    basic FUNCTION
  • promoting apoptosis by binding to caspase inhibitors of the IAP family (BIRCS) and preventing them from inhibiting caspases
  • activating caspases in the cytochrome C/APAF1/CASP9 pathway
  • involved in TNF-mediated CASP8 activation and apoptosis
  • playing an essential role in the apoptosis induced by non-steroidal anti-inflammatory drugs in colon cancer
  • IAP-binding protein that is released from mitochondria during apoptosis
  • potentiating apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activities
  • one of the proapoptotic proteins released from the mitochondria that inactivate IAPs and play a redundant role during development and cell death
  • play an obligatory role in the tumor cells during several pathways of apoptosis induction
  • mitochondrial apoptogenic protein, mediating the proapoptotic function of BBC3 by regulating BBC3-induced mitochondrial events
  • playing an important role in executing DNA damage-induced and BBC3-mediated apoptosis and can participates in a feedback amplification loop to promote cytochrome c release and other mitochondrial events in apoptosis
  • can target BIRC2 to induce TNFalpha-dependent apoptosis and so may have a role in treating cancer
  • DIABLO function, but not Caspase-9 activity, was decisive for full effector caspase activation and clonogenic execution of Type I cells
  • acing potentially to enhance the early phase executioner caspase activity through the modulation of inhibitory interactions between specific IAP family members and executioner CASP3 and CASP7
  • plays key roles in both the diagnosis and treatment of cancer, especially lung cancer
  • in addition to APAF1 or apoptosome formation, DIABLO is also essential for MTCH1-induced apoptosis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly binding to the BIR domain of IAPs (XIAP and others) nad interacting with CASP9
  • TNF, MAPK8, BID, CASP8 for TNF-induced apoptosis
  • interacting with UBE2K (promoted degradation of mature DIABLO through the ubiquitin proteasome pathway)
  • PRPS1 initiates caspase activation upstream of cytochrome C and DIABLO
  • inhibits apoptosis of breast cancer cells by suppression of BIRC5
  • in apoptosis, BIRC5 recognize the DIABLO protein
  • BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO
  • AREL1 interacted with and ubiquitinated IAP antagonists such as DIABLO, HTRA2, and PRPS1
  • intramembrane cleavage of DIABLO by PARL generates an N-terminal IAP-binding motif, which is required for its apoptotic activity
  • cell & other
    REGULATION
    activated by caspases
    inhibited by BCL2
    ASSOCIATED DISORDERS
    corresponding disease(s) DFNA64
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in mycosis fungoides (MF), the most frequent form of cutaneous T cell lymphoma
    constitutional     --low  
    alters both caspase-dependent and caspase-independent intrinsic programmed cell death
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    DIABLO mimetics can elicit a proinflammatory cell death that is sufficient to activate adaptive antitumor immune responses in cancer
    ANIMAL & CELL MODELS