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    DFFB DNA fragmentation factor subunit beta [ Homo sapiens (human) ]

    Gene ID: 1677, updated on 17-Jun-2024

    Summary

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    Official Symbol
    DFFBprovided by HGNC
    Official Full Name
    DNA fragmentation factor subunit betaprovided by HGNC
    Primary source
    HGNC:HGNC:2773
    See related
    Ensembl:ENSG00000169598 MIM:601883; AllianceGenome:HGNC:2773
    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
    CAD; CPAN; DFF2; DFF40; DFF-40
    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. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some of these variants has not been determined. [provided by RefSeq, Sep 2013]
    Expression
    Ubiquitous expression in duodenum (RPKM 1.4), spleen (RPKM 1.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DFFB in Genome Data Viewer
    Location:
    1p36.32
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (3857476..3885429)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (3369074..3397333)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (3774040..3801993)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 574, pseudogene Neighboring gene leucine rich repeat containing 47 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:3709930-3710608 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 125 Neighboring gene Sharpr-MPRA regulatory region 1968 Neighboring gene centrosomal protein 104 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:3745882-3747081 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:3747165-3748364 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:3755401-3755900 Neighboring gene uncharacterized LOC124903829 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:3767162-3767662 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 126 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 67 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 127 Neighboring gene Sharpr-MPRA regulatory region 4254 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:3787529-3787731 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 128 Neighboring gene chromosome 1 open reading frame 174 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:3815928-3816498 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:3816499-3817067 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:3817068-3817637 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 130 Neighboring gene long intergenic non-protein coding RNA 1134 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 131 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:3827787-3828672

    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
    • 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. Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse. Haimovici A, et al. Cell Death Dis, 2022 Apr 7. PMID 35393399, Free PMC Article
    2. DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway. Kulbay M, et al. Biochem Pharmacol, 2021 Dec. PMID 34678222
    3. The role of the DFF40/CAD endonuclease in genomic stability. Kulbay M, et al. Apoptosis, 2021 Feb. PMID 33387146
    4. An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells. Sánchez-Osuna M, et al. Neuro Oncol, 2016 Jul. PMID 26755073, Free PMC Article
    5. Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40. Bagheri F, et al. Biochem Cell Biol, 2015 Dec. PMID 26529233, Free PMC Article

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MEG3 Regulates CSE-Induced Apoptosis by Regulating miR-421/DFFB Signal Axis.
      Title: MEG3 Regulates CSE-Induced Apoptosis by Regulating miR-421/DFFB Signal Axis.
    2. Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse.
      Title: Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse.
    3. DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway.
      Title: DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway.
    4. The role of the DFF40/CAD endonuclease in genomic stability.
      Title: The role of the DFF40/CAD endonuclease in genomic stability.
    5. The Nexus of cfDNA and Nuclease Biology.
      Title: The Nexus of cfDNA and Nuclease Biology.
    6. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of endometrial polyps and benign endometrial hyperplasia
      Title: Endometrial Polyps and Benign Endometrial Hyperplasia Have Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria.
    7. we show that executioner caspase activation of the apoptotic nuclease CAD/DFF40 is essential for TRAIL-induced mutations in surviving cells. As exposure to chemotherapy drugs also activates apoptotic caspases and presumably CAD, we hypothesized that these pathways may also contribute to the mutagenesis induced by conventional chemotherapy drugs, perhaps augmenting the mutations that arise from direct DNA damage
      Title: Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine.
    8. Dff40 expression is upregulated in atherosclerotic plaque.
      Title: Loss of Caspase-Activated DNase Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice.
    9. the low expression levels of DFF40/CAD and the absence of DNA laddering as common molecular traits in glioblastoma
      Title: An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells.
    10. Data suggest DFF40 expression in breast cancer cell line is involved in drug sensitivity/resistance to doxorubicin; apoptotic cell death due to doxorubicin (a topoisomerase II inhibitor) is enhanced by DFF40 overexpression in breast cancer cell line.
      Title: Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    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 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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA endonuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA nuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA nuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables disordered domain specific binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein domain specific binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in apoptotic DNA fragmentation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within apoptotic DNA fragmentation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in apoptotic DNA fragmentation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in apoptotic chromosome condensation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic DNA fragmentation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    DNA fragmentation factor subunit beta
    Names
    DNA fragmentation factor 40 kDa subunit
    DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)
    caspase-activated DNase
    caspase-activated deoxyribonuclease
    caspase-activated nuclease

    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.

    mRNA and Protein(s)

    1. NM_001282669.2 → NP_001269598.1  DNA fragmentation factor subunit beta isoform 1

      See identical proteins and their annotated locations for NP_001269598.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AK303065, AL691523, BC032827
      Consensus CDS
      CCDS72693.1
      UniProtKB/TrEMBL
      B4DZS0
      Related
      ENSP00000339524.4, ENST00000338895.7
      Conserved Domains (2) summary
      cd06535
      Location:4 → 80
      CIDE_N_CAD; CIDE_N domain of CAD nuclease. The CIDE_N (cell death-inducing DFF45-like effector, N-terminal) domain is found at the N-terminus of CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD(DFF45). These proteins are ...
      pfam09230
      Location:124 → 347
      DFF40; DNA fragmentation factor 40 kDa

    2. NM_001320132.2 → NP_001307061.1  DNA fragmentation factor subunit beta isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region and uses an alternate start codon, compared to variant 1. It encodes isoform 4, which has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AB028912, AF409060, AK027141, BC032827
      UniProtKB/Swiss-Prot
      O76075
      UniProtKB/TrEMBL
      Q96P73, Q96P74
      Conserved Domains (1) summary
      pfam09230
      Location:51 → 274
      DFF40; DNA fragmentation factor 40 kDa

    3. NM_001320136.2 → NP_001307065.1  DNA fragmentation factor subunit beta isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region and uses a downstrean in-frame start codon, compared to variant 1. It encodes isoform 5, which is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AF409062, AK027141, BC032827, DC368011
      UniProtKB/TrEMBL
      Q96P72, Q96P73
      Conserved Domains (1) summary
      pfam09230
      Location:36 → 259
      DFF40; DNA fragmentation factor 40 kDa

    4. NM_004402.4 → NP_004393.1  DNA fragmentation factor subunit beta isoform 2

      See identical proteins and their annotated locations for NP_004393.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains two consecutive alternate splice junctions compared to variant 1. The resulting isoform (2) has the same N- and C-termini but lacks an internal segment compared to isoform 1.
      Source sequence(s)
      AL691523, BC032827, BC048797
      Consensus CDS
      CCDS52.1
      UniProtKB/Swiss-Prot
      O60521, O76075, Q5SR22, Q9BYI4, Q9BYI5, Q9BYI6
      Related
      ENSP00000367454.4, ENST00000378209.8
      Conserved Domains (2) summary
      cd06535
      Location:4 → 80
      CIDE_N_CAD; CIDE_N domain of CAD nuclease. The CIDE_N (cell death-inducing DFF45-like effector, N-terminal) domain is found at the N-terminus of CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD(DFF45). These proteins are ...
      pfam09230
      Location:100 → 323
      DFF40; DNA fragmentation factor 40 kDa

    RNA

    1. NR_104222.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice junction and contains an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL691523, BC032827
      Related
      ENST00000468793.5

    2. NR_135150.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses alternate splice sites in two internal exons and contains an additional internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB028911, AF409060, AK027141, AL691523, BC032827
      Related
      ENST00000491998.5

    3. NR_135151.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses alternate splice sites in two internal exons and contains an additional internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB028913, AF409060, AK027141, BC032827, CN275847
      Related
      ENST00000477548.5

    4. NR_135152.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AF409061, AK027141, BC032827, DC368011
      Related
      ENST00000475969.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      3857476..3885429
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017000499.2 → XP_016855988.1  DNA fragmentation factor subunit beta isoform X2

    2. XM_017000500.2 → XP_016855989.1  DNA fragmentation factor subunit beta isoform X3

    3. XM_017000498.3 → XP_016855987.1  DNA fragmentation factor subunit beta isoform X1

    4. XM_011540865.3 → XP_011539167.1  DNA fragmentation factor subunit beta isoform X4

      Conserved Domains (2) summary
      cd06535
      Location:4 → 80
      CIDE_N_CAD; CIDE_N domain of CAD nuclease. The CIDE_N (cell death-inducing DFF45-like effector, N-terminal) domain is found at the N-terminus of CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD(DFF45). These proteins are ...
      pfam09230
      Location:124 → 168
      DFF40; DNA fragmentation factor 40 kDa

    RNA

    1. XR_946563.3 RNA Sequence

    2. XR_946565.2 RNA Sequence

    3. XR_002959574.2 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      3369074..3397333
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334793.1 → XP_054190768.1  DNA fragmentation factor subunit beta isoform X2

    2. XM_054334794.1 → XP_054190769.1  DNA fragmentation factor subunit beta isoform X3

    3. XM_054334792.1 → XP_054190767.1  DNA fragmentation factor subunit beta isoform X1

    4. XM_054334795.1 → XP_054190770.1  DNA fragmentation factor subunit beta isoform X4

    RNA

    1. XR_008485941.1 RNA Sequence

    2. XR_008485943.1 RNA Sequence

    3. XR_008485942.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001004285.1: Suppressed sequence

      Description
      NM_001004285.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_001004286.1: Suppressed sequence

      Description
      NM_001004286.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O76075.1 GenPept UniProtKB/Swiss-Prot:O76075

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