DIABLO (Homo sapiens)
Description [+]
- Synonyms: DIABLO, SMAC, DIABLO-S, FLJ25049, FLJ10537
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Diablo homolog, mitochondrial Precursor (Second mitochondria-derived activator of caspase)(Smac protein)(Direct IAP-binding protein with low pI) [Source:UniProtKB/Swiss-Prot;Acc:Q9NR28]
- Family: IAP antagonist
- Process: apoptosis,
- Pathways: intrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Diablo
- WIKI: DIABLO-H_sapiens
References [+]
- Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.
- Du C, Fang M, Li Y, Li L, Wang X
- We report here the identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis. Mitochondrial import and cleavage of its signal peptide are required for Smac to gain its apoptotic activity. Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases. Cell. 2000 Jul 7;102(1):33-42.
- References from Mouse ortholog(s):
- Generation and characterization of Smac/DIABLO-deficient mice.
- Okada H, Suh WK, Jin J, Woo M, Du C, Elia A, Duncan GS, Wakeham A, Itie A, Lowe SW, Wang X, Mak TW
- The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function. These observations have suggested that Smac is a new regulator of apoptosis. To better understand the physiological function of Smac in normal cells, we generated Smac-deficient (Smac(-/-)) mice by using homologous recombination in embryonic stem (ES) cells. Smac(-/-) mice were viable, grew, and matured normally and did not show any histological abnormalities. Although the cleavage in vitro of procaspase-3 was inhibited in lysates of Smac(-/-) cells, all types of cultured Smac(-/-) cells tested responded normally to all apoptotic stimuli applied. There were also no detectable differences in Fas-mediated apoptosis in the liver in vivo. Our data strongly suggest the existence of a redundant molecule or molecules capable of compensating for a loss of Smac function. Mol Cell Biol. 2002 May;22(10):3509-17.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Smac_DIABLO | 6 | 239 |
Protein sequence [+]
DIABLO | Homo sapiens | 9606 | length:239
MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGVTLCAVPIA
QKSEPHSLSSEALMRRAVSLVTDSTSTFLSQTTYALIEAITEYTKAVYTLTSLYRQYTSL
LGKMNSEEEDEVWQVIIGARAEMTSKHQEYLKLETTWMTAVGLSEMAAEAAYQTGADQAS
ITARNHIQLVKLQVEEVHQLSRKAETKLAEAQIEELRQKTQEEGEERAESEQEAYLRED
QKSEPHSLSSEALMRRAVSLVTDSTSTFLSQTTYALIEAITEYTKAVYTLTSLYRQYTSL
LGKMNSEEEDEVWQVIIGARAEMTSKHQEYLKLETTWMTAVGLSEMAAEAAYQTGADQAS
ITARNHIQLVKLQVEEVHQLSRKAETKLAEAQIEELRQKTQEEGEERAESEQEAYLRED
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| DIABLO | orthology | Chicken |
| DIABLO | orthology | Chimpanzee |
| NP_001039347.1 | orthology | Cow |
| A1DZY5_CANFA | orthology | Dog |
| DIABLO | orthology | Gorilla |
| DIABLO | orthology | Horse |
| DIABLO | orthology | Lyzard |
| DIABLO | orthology | Monodelphis |
| Diablo | orthology | Mouse |
| DBLOH_PONPY | orthology | Orangutan |
| DIABLO | orthology | Ornithorhynchus |
| R_norvegicus_ENSRNOP00000011308 | orthology | Rat |
| Diablo | orthology | Rat |
| DIABLO | orthology | Xenopus |
| B5FY41_TAEGU | orthology | Zebra finch |
| zgc:158776 | orthology | Zebrafish |
| DIABLO (1 of 2) | paralogy | Fugu |
| DIABLO (2 of 2) | paralogy | Fugu |
| DIABLO (1 of 2) | paralogy | Gasterosteus |
| DIABLO (2 of 2) | paralogy | Gasterosteus |
| DIABLO (1 of 2) | paralogy | Medaka |
| DIABLO (2 of 2) | paralogy | Medaka |
| DIABLO (2 of 3) | paralogy | Tetraodon |
| DIABLO (1 of 3) | paralogy | Tetraodon |
| zgc:63938 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006917 | induction of apoptosis | biological_proccess | IEA |
| GO:0006919 | activation of caspase activity | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | TAS |
| GO:0008625 | induction of apoptosis via death domain receptors | biological_proccess | TAS |
| GO:0008635 | activation of caspase activity by cytochrome c | biological_proccess | TAS |
| GO:0043065 | positive regulation of apoptosis | biological_proccess | IEA |
| GO:0008631 | induction of apoptosis by oxidative stress | biological_proccess | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005739 | mitochondrion | cell_component | IEA |
| GO:0005739 | mitochondrion | cell_component | TAS |
| GO:0005829 | cytosol | cell_component | EXP |
| GO:0005737 | cytoplasm | cell_component | IEA |
Check GO Evidence Codes here
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :21528
- Gene related info from GeneCards [?] : DIABLO
- Ensembl genome browser [?] : ENSG00000184047
- Expression info from Arrayexpress [?] : ENSG00000184047
- Protein expression from Protein Atlas: [?] ENSG00000184047
- Community gene edition from Wikigenes: [?] 56616
- OMIM gene information: 605219
- OMIM disease information:
Click on [?] for more information.
