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    DFFA DNA fragmentation factor, 45kDa, alpha polypeptide [ Homo sapiens ]

    Gene ID: 1676, updated on 11-May-2012
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    Summary

    Official Symbol
    DFFAprovided by HGNC
    Official Full Name
    DNA fragmentation factor, 45kDa, alpha polypeptideprovided by HGNC
    Primary source
    HGNC:2772
    Locus tag
    H13
    See related
    Ensembl:ENSG00000160049; HPRD:03531; MIM:601882; Vega:OTTHUMG00000001909
    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
    DFF1; ICAD; DFF-45
    Summary
    Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    1p36.3-p36.2
    Sequence :
    Chromosome: 1; NC_000001.10 (10520588..10532613, complement)
    See DFFA in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene APITD1-CORT readthrough Neighboring gene apoptosis-inducing, TAF9-like domain 1 Neighboring gene cortistatin Neighboring gene peroxisomal biogenesis factor 14 Neighboring gene castor zinc finger 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    2. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    3. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Danielsen JM, et al. Mol Cell Proteomics, 2011 Mar. PMID 21139048.
    4. MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network. Zhang J, et al. Mol Cancer, 2010 Aug 6. PMID 20687965.
    5. Network organization of the human autophagy system. Behrends C, et al. Nature, 2010 Jul 1. PMID 20562859.

    See all (53) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. study reveals a previously unrecognized function of miR-145 in DFF45 processing, which may underlie crucial aspects of cancer biology
      Title: MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network.
    2. The heterodimer, DFF40-DFF45, is localized to the chromatin fraction under apoptotic as well as non-apoptotic conditions.
      Title: Histone H1 subtype preferences of DFF40 and possible nuclear localization of DFF40/45 in normal and trichostatin A-treated NB4 leukemic cells.
    3. A decreased level of DFF45 observed in ovarian endometriosis may be a part of an apoptosis-resistant mechanism enhancing the disease progression.
      Title: DFF45 expression in ovarian endometriomas.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.
    5. MPP(+) did not change the total levels of c-Jun but enhanced phosphorylation of c-Jun at Ser73 and cleavage of DNA fragmentation factor 45, which were diminished by selegiline.
      Title: 1-Methyl-4-phenyl-pyridinium ion-induced oxidative stress, c-Jun phosphorylation and DNA fragmentation factor-45 cleavage in SK-N-SH cells are averted by selegiline.
    6. The highest level of DFF45 endometrial expression was found during the early secretory cycle phase, and significantly lower DFF45 expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase.
      Title: The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.
    7. identified a TATA-less region upstream of the transcription start site as a basal promoter of the ICAD gene. An E-Box motif, which binds transcription factors of the basic helix-loop-helix/leucine zipper family, is responsible for transcriptional activity
      Title: Identification and characterization of the human inhibitor of caspase-activated DNase gene promoter.
    8. C-terminal region of each subunit, DFF40 (RLKRK) and DFF45 (KRAR), is essential for nuclear accumulation of the DFF complex.
      Title: Sequence elements in both subunits of the DNA fragmentation factor are essential for its nuclear transport.
    9. Interestingly, nuclear DNA fragmentation occurred and consistently DNA fragmentation factor (DFF45)/Inhibitor of caspase-activated DNase (ICAD) was cleaved inside the cell as well as in vitro, suggesting a role of caspase-2 in nuclear DNA fragmentation.
      Title: Caspase-2 cleaves DNA fragmentation factor (DFF45)/inhibitor of caspase-activated DNase (ICAD).
    10. demonstrate the cellular mechanisms of neuronal cell degeneration induced via c-Jun-N-terminal kinases and caspase-dependent signaling
      Title: Melatonin inhibits MPP+-induced caspase-mediated death pathway and DNA fragmentation factor-45 cleavage in SK-N-SH cultured cells.
    Submit: New GeneRIF Correction See all (17)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol HIV-1 protease directly cleaves and activates procaspase 8 in T cells, which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    O00273 P42574 CASP3    HPRD  PubMed  
    O00273 P55210 CASP7    HPRD  PubMed  
    O00273 Q9UHD4 CIDEB    HPRD  PubMed  
    O00273 O76075 DFFB    HPRD  PubMed  
    O00273 Q01844 EWSR1    HPRD  PubMed  
    O00273 P10144 GZMB    HPRD  PubMed  
    O00273 EF hand calcium binding protein 2 NECAB2    HPRD  PubMed  
    O00273 Q9NRL3 STRN4    HPRD  PubMed  
    O00273 P61981 YWHAG    HPRD  PubMed  
    O00273 P63104 YWHAZ    HPRD  PubMed  
    BioGRID:108040 BioGRID:107054 BAK1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:118027 CIDEB    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108040 BioGRID:108041 DFFB    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:108040 BioGRID:108431 EWSR1    BioGRID  PubMed Two-hybrid 
    BioGRID:108040 BioGRID:114439 HERC1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:110333 MCC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:129344 NAP1L5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:120035 NECAB2    BioGRID  PubMed Two-hybrid 
    BioGRID:108040 BioGRID:111550 PRKAA2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:119653 TMBIM4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:115283 USP15    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:113364 YWHAG    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:108040 BioGRID:113366 YWHAZ    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Activation of DNA fragmentation factor, organism-specific biosystem (from REACTOME)
      Activation of DNA fragmentation factor, organism-specific biosystemDNA fragmentation in response to apoptotic signals is achieved, in part, through the activity of apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) (reviewed ...
    • 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, organism-specific biosystem (from KEGG)
      Apoptosis, organism-specific biosystemApoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily me...
    • Apoptosis, conserved biosystem (from KEGG)
      Apoptosis, conserved biosystemApoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily me...
    • 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 induced DNA fragmentation, organism-specific biosystem (from REACTOME)
      Apoptosis induced DNA fragmentation, organism-specific biosystemDNA fragmentation in response to apoptotic signals is achieved through the activity of two apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) and endonuclease...
    • Apoptotic execution phase, organism-specific biosystem (from REACTOME)
      Apoptotic execution phase, organism-specific biosystemIn the execution phase of apoptosis, effector caspases cleave vital cellular proteins leading to the morphological changes that characterize apoptosis. These changes include destruction of the nucle...
    • Caspase cascade in apoptosis, organism-specific biosystem (from Pathway Interaction Database)
      Caspase cascade in apoptosis, organism-specific biosystem
      Caspase cascade in apoptosis
    • FAS pathway and Stress induction of HSP regulation, organism-specific biosystem (from WikiPathways)
      FAS pathway and Stress induction of HSP regulation, organism-specific biosystemThis pathway describes the Fas induced apoptosis and interplay with Hsp27 in response to stress. More info: [http://www.biocarta.com/pathfiles/h_hsp27Pathway.asp BioCarta].
    • HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem (from Pathway Interaction Database)
      HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem
      HIV-1 Nef: Negative effector of Fas and TNF-alpha

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    deoxyribonuclease activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    DNA fragmentation involved in apoptotic nuclear change IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    DNA fragmentation involved in apoptotic nuclear change TAS
    Traceable Author Statement
    more info
    		  
    apoptotic process TAS
    Traceable Author Statement
    more info
    		  
    cellular component disassembly involved in apoptosis TAS
    Traceable Author Statement
    more info
    		  
    induction of apoptosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    intracellular signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    nuclear chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    DNA fragmentation factor subunit alpha
    Names
    DNA fragmentation factor subunit alpha
    DFF45
    inhibitor of CAD
    DNA fragmentation factor 45 kDa subunit
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    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_029098.1 RefSeqGene

      Range
      5001..17026
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_004401.2 → NP_004392.1  DNA fragmentation factor subunit alpha isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shorter transcript but encodes the longer isoform (1).
      Source sequence(s)
      AU121791, BC000037, BC007112, BC007721
      Consensus CDS
      CCDS118.1
      UniProtKB/Swiss-Prot
      O00273
      UniProtKB/TrEMBL
      Q5T6G6
      Related
      ENSP00000366237, OTTHUMP00000001903, ENST00000377038, OTTHUMT00000005418
      Conserved Domains (2) summary
      cd06536
      Location:18 – 96
      Blast Score: 353
      CIDE_N_ICAD; CIDE_N domain of ICAD. The CIDE_N (cell death-inducing DFF45-like effector, N-terminal) domain is found at the N-terminus of the CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD (DFF45). These proteins are ...
      pfam09033
      Location:100 – 265
      Blast Score: 471
      DFF-C; DNA Fragmentation factor 45kDa, C terminal domain

    2. NM_213566.1 → NP_998731.1  DNA fragmentation factor subunit alpha isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an additional segment in the 3' region, as compared to variant 1. It encodes isoform 2 which has a shorter and distinct C-terminus, as compared to isoform 1.
      Source sequence(s)
      AF087573, AU121791, BC000037, BC007112, BC007721, BE207821, BU956486
      Consensus CDS
      CCDS119.1
      UniProtKB/Swiss-Prot
      O00273
      Related
      ENSP00000366235, OTTHUMP00000001904, ENST00000377036, OTTHUMT00000005419
      Conserved Domains (2) summary
      cd06536
      Location:18 – 96
      Blast Score: 356
      CIDE_N_ICAD; CIDE_N domain of ICAD. The CIDE_N (cell death-inducing DFF45-like effector, N-terminal) domain is found at the N-terminus of the CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD (DFF45). These proteins are ...
      pfam09033
      Location:100 – 261
      Blast Score: 469
      DFF-C; DNA Fragmentation factor 45kDa, C terminal domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      10520588..10532613, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      9674182..9686174, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL354956.13 CAI19196.1
      CAI19197.1
    genomic CH471130.1 EAW71655.1
      EAW71656.1
      EAW71657.1
      EAW71658.1
    mRNA AF087573.1 AAD32953.1
    mRNA AF103799.1 AAF02419.1
    mRNA AK222546.1 BAD96266.1
    mRNA AK313317.1 BAG36122.1
    mRNA AU121791.1 None
    mRNA BC000037.2 AAH00037.1
    mRNA BC007112.1 AAH07112.1
    mRNA BC007721.2 AAH07721.1
    mRNA BE207821.1 None
    mRNA BT006980.1 AAP35626.1
    mRNA BU956486.1 None
    mRNA U91985.1 AAC51249.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00273.1 GenPept UniProtKB/Swiss-Prot:O00273
    Q53HN4 GenPept UniProtKB/TrEMBL:Q53HN4
    Q5T6G6 GenPept UniProtKB/TrEMBL:Q5T6G6
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
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