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

Gene ID: 56616, updated on 9-Dec-2018

Summary

Official Symbol
DIABLOprovided by HGNC
Official Full Name
diablo IAP-binding mitochondrial proteinprovided by HGNC
Primary source
HGNC:HGNC:21528
See related
Ensembl:ENSG00000184047 Ensembl:ENSG00000284934 MIM:605219
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

Genomic context

See DIABLO in Genome Data Viewer
Location:
12q24.31
Exon count:
8
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (122207662..122227534, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (122692209..122712081, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene MLX interacting protein Neighboring gene leucine rich repeat containing 43 Neighboring gene interleukin 31 Neighboring gene uncharacterized LOC101593348 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4 Neighboring gene VPS33A, CORVET/HOPS core subunit Neighboring gene CAP-Gly domain containing linker protein 1 Neighboring gene coiled-coil domain containing 150 pseudogene 1

Genomic regions, transcripts, and products

Expression

  • Project title: 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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 BioSystems

  • Apoptosis, organism-specific biosystem (from KEGG)
    Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis, organism-specific biosystem (from WikiPathways)
    Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
  • Apoptosis, conserved biosystem (from KEGG)
    Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis, organism-specific biosystem (from REACTOME)
    Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
  • Apoptosis - multiple species, organism-specific biosystem (from KEGG)
    Apoptosis - multiple species, organism-specific biosystemApoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The ma...
  • Apoptosis - multiple species, conserved biosystem (from KEGG)
    Apoptosis - multiple species, conserved biosystemApoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The ma...
  • Apoptosis Modulation and Signaling, organism-specific biosystem (from WikiPathways)
    Apoptosis Modulation and Signaling, organism-specific biosystemApoptosis, or cell death program, can be activated by various mechanisms within the extrinsic and the intrinsic pathway. While activation of cell death receptors leads to the engagement of the extrin...
  • Apoptotic factor-mediated response, organism-specific biosystem (from REACTOME)
    Apoptotic factor-mediated response, organism-specific biosystemIn response to apoptotic signals, mitochondrial proteins are released into the cytosol and activate both caspase-dependent and -independent cell death pathways. Cytochrome c induces apoptosome form...
  • Caspase cascade in apoptosis, organism-specific biosystem (from Pathway Interaction Database)
    Caspase cascade in apoptosis, organism-specific biosystem
    Caspase cascade in apoptosis
  • Intrinsic Pathway for Apoptosis, organism-specific biosystem (from REACTOME)
    Intrinsic Pathway for Apoptosis, organism-specific biosystemThe intrinsic (Bcl-2 inhibitable or mitochondrial) pathway of apoptosis functions in response to various types of intracellular stress including growth factor withdrawal, DNA damage, unfolding stress...
  • Nanomaterial induced apoptosis, organism-specific biosystem (from WikiPathways)
    Nanomaterial induced apoptosis, organism-specific biosystemApotosis caused by nanomaterials, such as single-walled carbon nanohorns, titanium oxide, and polystyrene nanoparticles, may be induced through lysosomal impairment. For example, PAMAMs have been fou...
  • Programmed Cell Death, organism-specific biosystem (from REACTOME)
    Programmed Cell Death, organism-specific biosystemCell death is a fundamental cellular response that has a crucial role in shaping our bodies during development and in regulating tissue homeostasis by eliminating unwanted cells. There are a number o...
  • Release of apoptotic factors from the mitochondria, organism-specific biosystem (from REACTOME)
    Release of apoptotic factors from the mitochondria, organism-specific biosystemApoptotic factors released from the mitochondria promote apoptosis through several different mechanisms. Cytochrome C participates in Apoptosome driven effector caspase activation while SMAC relieves...
  • SMAC binds to IAPs, organism-specific biosystem (from REACTOME)
    SMAC binds to IAPs, organism-specific biosystemSMAC binds to the XIAP:caspase complexes.
  • SMAC-mediated apoptotic response, organism-specific biosystem (from REACTOME)
    SMAC-mediated apoptotic response, organism-specific biosystemOnce released from the mitochondria, SMAC binds to IAP family proteins displacing them from Caspase:IAP complexes liberating the active caspases.
  • SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystem (from REACTOME)
    SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystemSmac/DIABLO regulates IAP function. Residues 56-59 of Smac/DIABLO are homologous to the amino-terminal motif that is used by caspase-9 to bind to the BIR3 domain of XIAP. Binding of Smac/DIABLO to ...
  • TNF alpha Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF alpha Signaling Pathway, organism-specific biosystemTumor necrosis factor alpha (TNF?) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. T...
  • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
    p75(NTR)-mediated signaling, organism-specific biosystem
    p75(NTR)-mediated signaling

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Potential readthrough

Included gene: VPS33A

Homology

Clone Names

  • FLJ10537, FLJ25049, 0610041G12Rik

Gene Ontology Provided by GOA

Function Evidence Code Pubs
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Component Evidence Code Pubs
CD40 receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoplasmic side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol TAS
Traceable Author Statement
more info
 
mitochondrial intermembrane space TAS
Traceable Author Statement
more info
PubMed 
mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
 

General protein information

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

NCBI Reference Sequences (RefSeq)

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
    4988..24860
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001278302.1NP_001265231.1  diablo homolog, mitochondrial 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/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    K7X1S0, Q502X2
    Conserved Domains (1) summary
    pfam09057
    Location:6142
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases
  2. NM_001278303.1NP_001265232.1  diablo homolog, mitochondrial 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/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    A0A024RBT2
    Related
    ENSP00000411638.2, ENST00000413918.5
    Conserved Domains (1) summary
    pfam09057
    Location:1166
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases
  3. NM_001278304.1NP_001265233.1  diablo homolog, mitochondrial 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/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    Q502X2
    Conserved Domains (1) summary
    pfam09057
    Location:8186
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases
  4. NM_001278342.1NP_001265271.1  diablo homolog, mitochondrial 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/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    A0A0S2Z5P6
    Related
    ENSP00000320343.6, ENST00000353548.11
    Conserved Domains (1) summary
    pfam09057
    Location:9195
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases
  5. NM_019887.5NP_063940.1  diablo homolog, mitochondrial 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, DA910387, DA915183, N66735
    Consensus CDS
    CCDS9228.1
    UniProtKB/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    A0A0S2Z5U7
    Related
    ENSP00000398495.3, ENST00000443649.8
    Conserved Domains (1) summary
    pfam09057
    Location:9239
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases
  6. NM_138930.3NP_620308.1  diablo homolog, mitochondrial 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/Swiss-Prot
    Q9NR28
    UniProtKB/TrEMBL
    Q502X2
    Conserved Domains (1) summary
    pfam09057
    Location:8186
    Smac_DIABLO; Second Mitochondria-derived Activator of Caspases

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

    Range
    122207662..122227534 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.
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