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DIABLO diablo IAP-binding mitochondrial protein [ Homo sapiens (human) ]

Gene ID: 56616, updated on 2-Nov-2024

Summary

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Official Symbol
DIABLOprovided by HGNC
Official Full Name
diablo IAP-binding mitochondrial proteinprovided by HGNC
Primary source
HGNC:HGNC:21528
See related
Ensembl:ENSG00000184047 MIM:605219; AllianceGenome:HGNC:21528
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SMAC; DFNA64
Summary
This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
Expression
Ubiquitous expression in testis (RPKM 16.5), adrenal (RPKM 10.0) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See DIABLO in Genome Data Viewer
Location:
12q24.31
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (122207662..122227456, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (122203450..122223242, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (122692209..122712003, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7201 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7202 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122580754-122581254 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122581255-122581755 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122582507-122583160 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122583161-122583814 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7205 Neighboring gene Sharpr-MPRA regulatory region 11163 Neighboring gene MLX interacting protein Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122611084-122611596 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122611597-122612107 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:122614034-122615233 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122622713-122623575 Neighboring gene MPRA-validated peak2016 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122651061-122651663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7209 Neighboring gene leucine rich repeat containing 43 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5011 Neighboring gene interleukin 31 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122709001-122709906 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7210 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7211 Neighboring gene uncharacterized LOC101593348 Neighboring gene uncharacterized LOC128125816 Neighboring gene Sharpr-MPRA regulatory region 2179 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122711745-122712576 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4 Neighboring gene VPS33A core subunit of CORVET and HOPS complexes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122750160-122751042 Neighboring gene MPRA-validated peak2017 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:122773535-122773694 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7214 Neighboring gene CAP-Gly domain containing linker protein 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122797254-122797754 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122797755-122798255 Neighboring gene coiled-coil domain containing 150 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Effect of Smac on TRAIL-induced apoptosis of prostate cancer cell line PC-3 and the molecular mechanism. Wang M, et al. J Huazhong Univ Sci Technolog Med Sci, 2012 Apr. PMID 22528226
  2. 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. Sun XM, et al. J Biol Chem, 2002 Mar 29. PMID 11801595
  3. Downregulation of Smac attenuates H2O2-induced apoptosis via endoplasmic reticulum stress in human lens epithelial cells. De-Qian K, et al. Medicine (Baltimore), 2017 Jul. PMID 28682901, Free PMC Article
  4. Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms. Kim DS, et al. Nat Commun, 2017 Aug 24. PMID 28839138, Free PMC Article
  5. The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells. Springs SL, et al. J Biol Chem, 2002 Nov 29. PMID 12364342

See all (290) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. In vivo and in vitro studies on the role of regulating Smac expression in the occurrence and development of colon cancer.
    Title: In vivo and in vitro studies on the role of regulating Smac expression in the occurrence and development of colon cancer.
  2. AREL1 resists the apoptosis induced by TGF-beta by inhibiting SMAC in vascular endothelial cells.
    Title: AREL1 resists the apoptosis induced by TGF-β by inhibiting SMAC in vascular endothelial cells.
  3. Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.
    Title: Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.
  4. Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases.
    Title: Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases.
  5. LINC-DUBR Suppresses Malignant Progression of Ovarian Cancer by Downregulating miR-107 to Induce SMAC Expression.
    Title: LINC-DUBR Suppresses Malignant Progression of Ovarian Cancer by Downregulating miR-107 to Induce SMAC Expression.
  6. Co-overexpression of TRAIL and Smac sensitizes MDA-MB-231 cells to radiation through apoptosis depending on mitochondrial pathway.
    Title: Co-overexpression of TRAIL and Smac sensitizes MDA-MB-231 cells to radiation through apoptosis depending on mitochondrial pathway.
  7. Mitochondria and nucleus cross-talk: Signaling in metabolism, apoptosis, and differentiation, and function in cancer.
    Title: Mitochondria and nucleus cross-talk: Signaling in metabolism, apoptosis, and differentiation, and function in cancer.
  8. BAX and SMAC regulate bistable properties of the apoptotic caspase system.
    Title: BAX and SMAC regulate bistable properties of the apoptotic caspase system.
  9. Biophysical characterization of the interaction between the full-length XIAP and Smac/DIABLO.
    Title: Biophysical characterization of the interaction between the full-length XIAP and Smac/DIABLO.
  10. Induction of interferon-beta and interferon signaling by TRAIL and Smac mimetics via caspase-8 in breast cancer cells.
    Title: Induction of interferon-β and interferon signaling by TRAIL and Smac mimetics via caspase-8 in breast cancer cells.
Submit: New GeneRIF Correction See all GeneRIFs (150)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Autosomal dominant nonsyndromic hearing loss 64
MedGen: C3279948 OMIM: 614152 GeneReviews: Not available
not available

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vpr vpr HIV-1 Vpr-induced apoptosis through caspase activation and Smac release from mitochondria is dependent on G2 cell cycle arrest , but is lost in cells synchronized in G1/S PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: VPS33A

Homology

Clone Names

  • FLJ10537, FLJ25049, 0610041G12Rik

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c TAS
Traceable Author Statement
more info
 PubMed 
involved_in apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in extrinsic apoptotic signaling pathway via death domain receptors TAS
Traceable Author Statement
more info
 PubMed 
involved_in intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in intrinsic apoptotic signaling pathway in response to oxidative stress IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in neuron apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
part_of CD40 receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytoplasmic side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in mitochondrial intermembrane space TAS
Traceable Author Statement
more info
 PubMed 
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
diablo IAP-binding mitochondrial protein
Names
diablo homolog, mitochondrial
diablo-like protein
direct IAP-binding protein with low pI
second mitochondria-derived activator of caspase
second mitochondria-derived activator of caspases

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029459.1 RefSeqGene

    Range
    6470..24854
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001278302.1 → NP_001265231.1  diablo IAP-binding mitochondrial protein isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in its 5' UTR and 5' coding region, uses an alternate start codon, and lacks an in-frame exon in the internal coding region, compared to variant 1. The encoded isoform (4) has a distinct N-terminus and is shorter, compared to isoform 1.
    Source sequence(s)
    AK057778, BC046209, BC095468, DA877400, JX679472, N66735
    UniProtKB/TrEMBL
    K7X1S0
    Conserved Domains (1) summary
    pfam09057
    Location:6 → 142
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  2. NM_001278303.1 → NP_001265232.1  diablo IAP-binding mitochondrial protein isoform 5

    See identical proteins and their annotated locations for NP_001265232.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (5, also known as Smac-gamma) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AK057778, BC046209, BF313712, DA877400, N66735
    Consensus CDS
    CCDS73541.1
    UniProtKB/TrEMBL
    K7X1S0
    Conserved Domains (1) summary
    pfam09057
    Location:1 → 166
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  3. NM_001278304.2 → NP_001265233.1  diablo IAP-binding mitochondrial protein isoform 2

    See identical proteins and their annotated locations for NP_001265233.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) differs in its 5' UTR and 5' coding region, and uses an alternate start codon, compared to variant 1. The encoded isoform (2, also known as Smac-beta and Smac/DIABLO-S) has a shorter and distinct N-terminus, compared to isoform 1. Isoform 2 has a cortical, instead of a mitochondrial, subcellular distribution, and lacks the inhibitor of apoptosis protein-binding domain but maintains the ability to potentiate apoptosis (PMID: 11285287). Variants 2 and 7 encode the same isoform.
    Source sequence(s)
    AK001399, AK057778, DB254800, N66735
    UniProtKB/TrEMBL
    Q502X2
    Related
    ENST00000644509.1
    Conserved Domains (1) summary
    pfam09057
    Location:8 → 186
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  4. NM_001278342.1 → NP_001265271.1  diablo IAP-binding mitochondrial protein isoform 3

    See identical proteins and their annotated locations for NP_001265271.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has a shorter 5' UTR, and lacks an alternate in-frame exon in the coding region, compared to variant 1. The encoded isoform (3, also known as Smac-delta and Smac3) is shorter, compared to isoform 1.
    Source sequence(s)
    AK057778, AY313210, BC046209, DA877400, N66735
    Consensus CDS
    CCDS9229.1
    UniProtKB/TrEMBL
    A0A0S2Z5P6, Q53HB7
    Related
    ENSP00000320343.6, ENST00000353548.11
    Conserved Domains (1) summary
    pfam09057
    Location:9 → 195
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  5. NM_001371333.1 → NP_001358262.1  diablo IAP-binding mitochondrial protein isoform 1 precursor

    Status: REVIEWED

    Source sequence(s)
    AC048338, AF262240
    Consensus CDS
    CCDS9228.1
    UniProtKB/Swiss-Prot
    B2RDQ0, Q6W3F3, Q96LV0, Q9BT11, Q9HAV6, Q9NR28
    UniProtKB/TrEMBL
    A0A0S2Z5U7, Q53HB7
    Related
    ENSP00000442360.2, ENST00000464942.7
    Conserved Domains (1) summary
    pfam09057
    Location:9 → 239
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  6. NM_019887.6 → NP_063940.1  diablo IAP-binding mitochondrial protein isoform 1 precursor

    See identical proteins and their annotated locations for NP_063940.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1, also known as Smac-alpha).
    Source sequence(s)
    AK057778, BC046209, DA915183, N66735
    Consensus CDS
    CCDS9228.1
    UniProtKB/Swiss-Prot
    B2RDQ0, Q6W3F3, Q96LV0, Q9BT11, Q9HAV6, Q9NR28
    UniProtKB/TrEMBL
    A0A0S2Z5U7, Q53HB7
    Conserved Domains (1) summary
    pfam09057
    Location:9 → 239
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

  7. NM_138930.3 → NP_620308.1  diablo IAP-binding mitochondrial protein isoform 2

    See identical proteins and their annotated locations for NP_620308.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in its 5' UTR and 5' coding region, and uses an alternate start codon, compared to variant 1. The encoded isoform (2, also known as Smac-beta and Smac/DIABLO-S) has a shorter and distinct N-terminus, compared to isoform 1. Isoform 2 has a cortical, instead of a mitochondrial, subcellular distribution, and lacks the inhibitor of apoptosis protein-binding domain but maintains the ability to potentiate apoptosis (PMID: 11285287). Variants 2 and 7 encode the same isoform.
    Source sequence(s)
    AK057778, BC046209, BC095468, DA877400, N66735
    UniProtKB/TrEMBL
    Q502X2
    Conserved Domains (1) summary
    pfam09057
    Location:8 → 186
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    122207662..122227456 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    122203450..122223242 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_138929.3: Suppressed sequence

    Description
    NM_138929.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NR28.1 GenPept UniProtKB/Swiss-Prot:Q9NR28

Gene LinkOut

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