DIABLO (Diablo IAP-Binding Mitochondrial Protein)
A pro-apoptotic mitochondrial protein that neutralizes inhibitor of apoptosis proteins (IAPs) to promote caspase activation and programmed cell death.
Gene Information Card
| Symbol | DIABLO |
|---|---|
| Full Name | Diablo IAP-Binding Mitochondrial Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 56616 ncbi.nlm.nih.gov/gene/56616 |
| Ensembl ID | ENSG00000184047 |
| UniProt ID | Q9NR28 |
| OMIM ID | 605219 |
| HGNC ID | 21528 |
| Aliases | SMAC, SMAC3, DFNA64, FLJ10537 |
Description
DIABLO (also known as SMAC) encodes a mitochondrial protein that is released into the cytosol during apoptosis. It binds to inhibitor of apoptosis proteins (IAPs), such as XIAP, and neutralizes their caspase-inhibitory activity, thereby promoting caspase activation and cell death. The gene is located on chromosome 12q24.31 and is widely expressed in normal tissues. Dysregulation of DIABLO expression has been implicated in various cancers and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Reduced DIABLO expression or sequestration in mitochondria leads to IAP-mediated evasion of apoptosis, promoting tumor survival. | PMID: 12646205, COSMIC |
| Deafness, autosomal dominant 64 (DFNA64) | Missense mutations in DIABLO cause progressive hearing loss, likely due to altered mitochondrial function and apoptosis in cochlear cells. | OMIM 605219, PMID: 20881296 |
| Neurodegenerative disorders | Impaired DIABLO release may contribute to neuronal cell death in conditions such as Alzheimer's disease. | PMID: 15094067 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 5.2 | Low |
| Brain (cerebellum) | 8.1 | Medium |
| Heart | 6.4 | Medium |
| Kidney | 7.9 | Medium |
| Liver | 9.3 | Medium |
| Lung | 6.8 | Medium |
| Skeletal muscle | 4.5 | Low |
| Testis | 12.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Cervical cancer cell line |
| HEK 293 | 9.8 | Embryonic kidney cells |
| MCF7 | 7.2 | Breast cancer cell line |
| A549 | 8.0 | Lung cancer cell line |
| K562 | 6.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; reduced protein expression |
| c.202C>T (p.Arg68Trp) | Missense | <0.01% | Associated with DFNA64; altered IAP binding |
| c.341G>A (p.Arg114His) | Missense | <0.01% | Reported in COSMIC; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair DIABLO release from mitochondria or reduce IAP binding (e.g., p.Arg68Trp) lead to decreased apoptosis and may promote cancer or hearing loss.
Gain of Function (GOF)
Not well documented; overexpression of wild-type DIABLO can sensitize cells to apoptosis.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg68Trp) may interfere with wild-type DIABLO function, acting in a dominant-negative manner in hearing loss.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis (KEGG hsa04210)
• Intrinsic Pathway for Apoptosis (Reactome R-HSA-109606)
• SMAC-mediated dissociation of IAP:caspase complexes (Reactome R-HSA-111459)
Protein Summary
DIABLO (SMAC) is a 239-amino-acid mitochondrial protein that undergoes proteolytic processing to remove the N-terminal mitochondrial targeting sequence, exposing an IAP-binding motif (AVPI). The mature protein is released into the cytosol upon apoptotic stimuli, where it binds to IAPs (e.g., XIAP, cIAP1, cIAP2) and relieves their inhibition of caspases-3, -7, and -9. This promotes the execution phase of apoptosis. DIABLO also participates in non-apoptotic functions, including regulation of mitochondrial dynamics and autophagy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DIABLO Knockout HEK293 Cell Line | EDJ-KQ51537 | Human | 56616 | Details Get a Quote |
| DIABLO Knockout HeLa Cell Line | EDJ-KQ56742 | Human | 56616 | Details Get a Quote |
| DIABLO Knockout A-549 Cell Line | EDJ-KQ65247 | Human | 56616 | Details Get a Quote |
| DIABLO Knockout HCT 116 Cell Line | EDJ-KQ73688 | Human | 56616 | Details Get a Quote |
