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

    Gene ID: 56616, updated on 10-Dec-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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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 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 
    involved_in positive regulation of cysteine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of cysteine-type endopeptidase activity 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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    NEW Try the new Transcript table

    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

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