DFFA

DFFA

Identifiers Symbols DFFA; DFF-45; DFF1; ICAD External IDs OMIM: 601882 MGI: 1196227 HomoloGene: 3240 GeneCards: DFFA Gene

Gene Ontology
Molecular function	• deoxyribonuclease activity
Cellular component	• nuclear chromatin • nucleus • nucleoplasm • cytoplasm • cytosol
Biological process	• apoptotic DNA fragmentation • apoptotic process • induction of apoptosis • cellular component disassembly involved in execution phase of apoptosis • intracellular signal transduction • negative regulation of apoptotic process
Sources: Amigo / QuickGO

RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 1676 13347 Ensembl ENSG00000160049 ENSMUSG00000028974 UniProt O00273 O54786 RefSeq (mRNA) NM_004401 NM_001025296 RefSeq (protein) NP_004392 NP_001020467 Location (UCSC) Chr 1:
10.52 – 10.53 Mb Chr 4:
149.1 – 149.12 Mb PubMed search

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
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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.

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.

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.