DFFA DNA fragmentation factor subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: DFFAprovided by HGNC
Official Full Name: DNA fragmentation factor subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:2772
See related: Ensembl:ENSG00000160049 MIM:601882; AllianceGenome:HGNC:2772
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]
Expression: Ubiquitous expression in placenta (RPKM 6.3), kidney (RPKM 5.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.22

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (10456522..10472529, complement)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (10000139..10016137, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (10516579..10532586, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
evaluate the relative expression levels of miR-196a2 and three of its selected apoptosis-related targets; ANXA1, DFFA and PDCD4 in a sample of GI cancer patients
Title: Evaluation of miRNA-196a2 and apoptosis-related target genes: ANXA1, DFFA and PDCD4 expression in gastrointestinal cancer patients: A pilot study.
Data show that the caspase-activated DNase (CAD) is activated when caspases cleave its endogenous inhibitor ICAD, resulting in the characteristic DNA laddering of apoptosis.
Title: Engineered cellular gene-replacement platform for selective and inducible proteolytic profiling.
Data suggest that DFF45 gene silencing, when applied in combination with doxorubicin, may offer a therapeutic strategy for the treatment of breast cancer.
Title: siRNA-mediated knock-down of DFF45 amplifies doxorubicin therapeutic effects in breast cancer cells.
ICAD deficiency was associated with severe genomic instability.
Title: ICAD deficiency in human colon cancer and predisposition to colon tumorigenesis: linkage to apoptosis resistance and genomic instability.
mRNA splicing is actively driven toward the pro-apoptotic isoforms of Bim, Bcl-x, and ICAD in Pnn-depleted MCF-7 cells.
Title: Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD.
The DFF45 level in human endometrium corresponds to the respective phase of the menstrual cycle and decreases significantly after menopause.
Title: DFF45 expression in human endometrium is associated with menstrual cycle phases and decreases after menopause.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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

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
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

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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

D11S2921 (e-PCR)
- UniSTS:152074

GDB:434012 (e-PCR)
- UniSTS:157204

D11S2560 (e-PCR)
- UniSTS:37928

L17705 (e-PCR)
- UniSTS:66091

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

DFFA_3964 (e-PCR)
- UniSTS:462153

D1S1423 (e-PCR)
- UniSTS:149619

D11S3732 (e-PCR)
- UniSTS:152962

L17877 (e-PCR)
- UniSTS:61334

L17809 (e-PCR)
- UniSTS:39087

L17971 (e-PCR)
- UniSTS:43966

SHGC-74201 (e-PCR)
- UniSTS:2273

D3S1673 (e-PCR)
- UniSTS:148450

Homology

Homologs of the DFFA gene: The DFFA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 502 organisms have orthologs with human gene DFFA
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables deoxyribonuclease inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables molecular adaptor activity	EXP Inferred from Experiment 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
enables protein folding chaperone	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic DNA fragmentation	IEA Inferred from Electronic Annotation more info
involved_in chaperone-mediated protein folding	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic DNA fragmentation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic DNA fragmentation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of deoxyribonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of execution phase of apoptosis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in thymocyte apoptotic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in 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 nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
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 alpha

Names: DFF45; DNA fragmentation factor 45 kDa subunit; DNA fragmentation factor, 45kDa, alpha polypeptide; inhibitor of CAD

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

NG_029098.2 RefSeqGene

Range

5000..21007

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004401.3 → NP_004392.1 DNA fragmentation factor subunit alpha isoform 1

See identical proteins and their annotated locations for NP_004392.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript but encodes the longer isoform (1).

Source sequence(s)

AL354956, AU121791, BC000037, BC007112, BC007721

Consensus CDS

CCDS118.1

UniProtKB/Swiss-Prot

O00273, Q9Y6C6

Related

ENSP00000366237.3, ENST00000377038.8

Conserved Domains (2) summary

pfam09033
Location:100 → 264

DFF-C; DNA Fragmentation factor 45kDa, C terminal domain

cl02541
Location:18 → 96

CIDE_N; CIDE_N domain, found at the N-terminus of the CIDE (cell death-inducing DFF45-like effector) proteins, as well as CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD(DFF45). These proteins are associated with ...
NM_213566.2 → NP_998731.1 DNA fragmentation factor subunit alpha isoform 2

See identical proteins and their annotated locations for NP_998731.1

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

UniProtKB/TrEMBL

A0A024R4H5

Related

ENSP00000366235.2, ENST00000377036.2

Conserved Domains (2) summary

pfam09033
Location:100 → 261

DFF-C; DNA Fragmentation factor 45kDa, C terminal domain

cl02541
Location:18 → 96

CIDE_N; CIDE_N domain, found at the N-terminus of the CIDE (cell death-inducing DFF45-like effector) proteins, as well as CAD nuclease (caspase-activated DNase/DNA fragmentation factor, DFF40) and its inhibitor, ICAD(DFF45). These proteins are associated with ...