DFFA

DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in humans is encoded by the DFFA gene.^[5][6][7]

DFFA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IBX, 1IYR, 1KOY
Identifiers
Aliases	DFFA, DFF-45, DFF1, ICAD, DNA fragmentation factor subunit alpha
External IDs	OMIM: 601882; MGI: 1196227; HomoloGene: 3240; GeneCards: DFFA; OMA:DFFA - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.22 Start 10,456,522 bp[1] End 10,472,529 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 E2 Start 149,188,603 bp[2] End 149,205,104 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in internal globus pallidus inferior ganglion of vagus nerve nipple cardia ventral tegmental area cartilage tissue stromal cell of endometrium renal medulla subthalamic nucleus islet of Langerhans Top expressed in soleus muscle yolk sac medulla oblongata lip pons quadriceps femoris muscle zone of skin muscle of thigh primary motor cortex tibialis anterior muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein domain specific binding protein folding chaperone activity deoxyribonuclease inhibitor activity Cellular component cytosol lipid droplet intracellular anatomical structure nucleus nucleoplasm cytoplasm plasma membrane Biological process positive regulation of apoptotic process negative regulation of execution phase of apoptosis negative regulation of apoptotic DNA fragmentation apoptotic DNA fragmentation thymocyte apoptotic process apoptotic process negative regulation of deoxyribonuclease activity chaperone-mediated protein folding Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1676 13347 Ensembl ENSG00000160049 ENSMUSG00000028974 UniProt O00273 O54786 RefSeq (mRNA) NM_213566 NM_004401 NM_001025296 NM_010044 RefSeq (protein) NP_004392 NP_998731 NP_998731.1 NP_001020467 NP_034174 Location (UCSC) Chr 1: 10.46 – 10.47 Mb Chr 4: 149.19 – 149.21 Mb PubMed search [3] [4]
Wikidata
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DNA Fragmentation factor 45kDa, C terminal domain
nmr structure of dff-c domain
Identifiers
Symbol	DFF-C
Pfam	PF09033
InterPro	IPR015121
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure 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.^[7]

The C-terminal domain of DFFA (DFF-C) consists of four alpha-helices, which are folded in a helix-packing arrangement, with alpha-2 and alpha-3 packing against a long C-terminal helix (alpha-4). The main function of this domain is the inhibition of DFFB by binding to its C-terminal catalytic domain through ionic interactions, thereby inhibiting the fragmentation of DNA in the apoptotic process. In addition to blocking the DNase activity of DFFB, the C-terminal region of DFFA is also important for the DFFB-specific folding chaperone activity, as demonstrated by the ability of DFFA to refold DFFB.^[8]

Interactions

DFFA has been shown to interact with DFFB.^[9][10]