DFFA

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DFFA
Protein DFFA PDB 1iyr.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DFFA, DFF-45, DFF1, ICAD, DNA fragmentation factor subunit alpha
External IDs MGI: 1196227 HomoloGene: 3240 GeneCards: DFFA
RNA expression pattern
PBB GE DFFA 203277 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_213566
NM_004401

NM_001025296
NM_010044

RefSeq (protein)

NP_004392
NP_998731
NP_998731.1

NP_001020467.1
NP_001020467
NP_034174

Location (UCSC) Chr 1: 10.46 – 10.47 Mb Chr 4: 149.1 – 149.12 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse
DNA Fragmentation factor 45kDa, C terminal domain
PDB 1koy EBI.jpg
nmr structure of dff-c domain
Identifiers
Symbol DFF-C
Pfam PF09033
InterPro IPR015121

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.[3][4][5]

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.[5]

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.[6]

Interactions[edit]

DFFA has been shown to interact with DFFB.[7][8]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Leek JP, Carr IM, Bell SM, Markham AF, Lench NJ (Jun 1998). "Assignment of the DNA fragmentation factor gene (DFFA) to human chromosome bands 1p36.3→p36.2 by in situ hybridization". Cytogenet Cell Genet. 79 (3–4): 212–3. doi:10.1159/000134725. PMID 9605855. 
  4. ^ Liu X, Zou H, Slaughter C, Wang X (May 1997). "DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis". Cell. 89 (2): 175–84. doi:10.1016/S0092-8674(00)80197-X. PMID 9108473. 
  5. ^ a b "Entrez Gene: DFFA DNA fragmentation factor, 45kDa, alpha polypeptide". 
  6. ^ Fukushima K, Kikuchi J, Koshiba S, Kigawa T, Kuroda Y, Yokoyama S (August 2002). "Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation". J. Mol. Biol. 321 (2): 317–27. doi:10.1016/S0022-2836(02)00588-0. PMID 12144788. 
  7. ^ Ewing, Rob M; Chu Peter; Elisma Fred; Li Hongyan; Taylor Paul; Climie Shane; McBroom-Cerajewski Linda; Robinson Mark D; O'Connor Liam; Li Michael; Taylor Rod; Dharsee Moyez; Ho Yuen; Heilbut Adrian; Moore Lynda; Zhang Shudong; Ornatsky Olga; Bukhman Yury V; Ethier Martin; Sheng Yinglun; Vasilescu Julian; Abu-Farha Mohamed; Lambert Jean-Philippe; Duewel Henry S; Stewart Ian I; Kuehl Bonnie; Hogue Kelly; Colwill Karen; Gladwish Katharine; Muskat Brenda; Kinach Robert; Adams Sally-Lin; Moran Michael F; Morin Gregg B; Topaloglou Thodoros; Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. England. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948Freely accessible. PMID 17353931. 
  8. ^ McCarty, J S; Toh S Y; Li P (Oct 1999). "Study of DFF45 in its role of chaperone and inhibitor: two independent inhibitory domains of DFF40 nuclease activity". Biochem. Biophys. Res. Commun. UNITED STATES. 264 (1): 176–80. doi:10.1006/bbrc.1999.1497. ISSN 0006-291X. PMID 10527860. 

Further reading[edit]


This article incorporates text from the public domain Pfam and InterPro IPR015121