DFFA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDFFA, DFF-45, DFF1, ICAD, DNA fragmentation factor subunit alpha
External IDsOMIM: 601882 MGI: 1196227 HomoloGene: 3240 GeneCards: DFFA
Orthologs
SpeciesHumanMouse
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 MbChr 4: 149.19 – 149.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
DNA Fragmentation factor 45kDa, C terminal domain
nmr structure of dff-c domain
Identifiers
SymbolDFF-C
PfamPF09033
InterProIPR015121
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure 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.[5][6][7]

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]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000160049 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028974 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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". Cytogenetics and Cell Genetics. 79 (3–4): 212–3. doi:10.1159/000134725. PMID 9605855.
  6. Liu X, Zou H, Slaughter C, Wang X (April 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. S2CID 14800864.
  7. 1 2 "Entrez Gene: DFFA DNA fragmentation factor, 45kDa, alpha polypeptide".
  8. 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". Journal of Molecular Biology. 321 (2): 317–27. doi:10.1016/S0022-2836(02)00588-0. PMID 12144788.
  9. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  10. McCarty JS, Toh SY, Li P (October 1999). "Study of DFF45 in its role of chaperone and inhibitor: two independent inhibitory domains of DFF40 nuclease activity". Biochemical and Biophysical Research Communications. 264 (1): 176–80. doi:10.1006/bbrc.1999.1497. PMID 10527860.

Further reading

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