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2  structures 35  species 0  interactions 60  sequences 2  architectures

Family: DFF-C (PF09033)

Summary: DNA Fragmentation factor 45kDa, C terminal domain

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This is the Wikipedia entry entitled "DFFA". More...

DFFA Edit Wikipedia article

DNA fragmentation factor, 45kDa, alpha polypeptide

PDB rendering based on 1iyr.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DFFA; DFF-45; DFF1; ICAD
External IDs OMIM601882 MGI1196227 HomoloGene3240 GeneCards: DFFA Gene
RNA expression pattern
PBB GE DFFA 203277 at tn.png
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 [1] [2]
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.[1][2][3]

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.[3]

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.[4]

Interactions[edit]

DFFA has been shown to interact with DFFB.[5][6]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b "Entrez Gene: DFFA DNA fragmentation factor, 45kDa, alpha polypeptide". 
  4. ^ 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. 
  5. ^ 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 1847948. PMID 17353931. 
  6. ^ 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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

DNA Fragmentation factor 45kDa, C terminal domain Provide feedback

The C terminal domain of DNA Fragmentation factor 45kDa (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 DFF40 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 DFF40, the C-terminal region of DFF45 is also important for the DFF40-specific folding chaperone activity, as demonstrated by the ability of DFF45 to refold DFF40 [1].

Literature references

  1. Fukushima K, Kikuchi J, Koshiba S, Kigawa T, Kuroda Y, Yokoyama S; , J Mol Biol. 2002;321:317-327.: Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation. PUBMED:12144788 EPMC:12144788


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR015121

The C-terminal domain of DNA fragmentation factor 45 kDa (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 DFF40 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 DFF40, the C-terminal region of DFF45 is also important for the DFF40-specific folding chaperone activity, as demonstrated by the ability of DFF45 to refold DFF40 [PUBMED:12144788].

Domain organisation

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Alignments

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Representative proteomes NCBI
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RP55
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RP75
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(5)
Full
(60)
Representative proteomes NCBI
(53)
Meta
(0)
RP15
(2)
RP35
(4)
RP55
(11)
RP75
(30)
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Curation and family details

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Seed source: pdb_1iyr
Previous IDs: none
Type: Domain
Author: Mistry J, Sammut SJ
Number in seed: 5
Number in full: 60
Average length of the domain: 163.20 aa
Average identity of full alignment: 61 %
Average coverage of the sequence by the domain: 53.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 39.8 39.3
Noise cut-off 23.2 22.4
Model length: 164
Family (HMM) version: 5
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Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DFF-C domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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