Reviewed,
UniProtKB/Swiss-Prot O00273 (DFFA_HUMAN)
Last modified
February 9, 2010.
Version 109.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: DNA fragmentation factor subunit alpha Alternative name(s): DNA fragmentation factor 45 kDa subunit Short name=DFF-45 Inhibitor of CAD Short name=ICAD | ||||||
| Gene names |
| ||||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 331 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Inhibitor of the caspase-activated DNase (DFF40). |
| Subunit structure | Heterodimer of DFFA and DFFB. |
| Subcellular location | |
| Post-translational modification | Caspase-3 cleaves DFF45 at 2 sites to generate an active factor. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 |
| Sequence similarities | Contains 1 CIDE-N domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing |
| PTM | Acetylation Phosphoprotein |
| Technical term | 3D-structure Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | DNA fragmentation involved in apoptosis Ref.1 Inferred from direct assay. Source: MGI intracellular signaling cascade Ref.1Traceable author statement. Source: ProtInc negative regulation of apoptosisInferred from direct assay. Source: UniProtKB |
| Cellular component | cytosol Ref.1 Inferred from Experiment. Source: Reactome nucleoplasm Ref.1Inferred from Experiment. Source: Reactome |
| Molecular function | caspase-activated deoxyribonuclease activity Ref.1 Traceable author statement. Source: ProtInc identical protein bindingInferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 1 | EBI-727171,EBI-727171 | ||
| BAK1 | Q16611 | 1 | EBI-727171,EBI-519866 | |
| DFFB | O76075 | 1 | EBI-727171,EBI-1053821 | |
| MCC | P23508 | 1 | EBI-727171,EBI-307531 | |
| NAP1L5 | Q96NT1 | 1 | EBI-727171,EBI-713627 | |
| TMBIM4 | Q9HC24 | 1 | EBI-727171,EBI-1045545 | |
| USP15 | Q9Y4E8 | 1 | EBI-727171,EBI-1043104 | |
| YWHAZ | P63104 | 1 | EBI-727171,EBI-347088 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform DFF45 (identifier: O00273-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform DFF35 (identifier: O00273-2) The sequence of this isoform differs from the canonical sequence as follows: 262-268: LVTKEDP → VGGNQGH 269-331: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 331 | 331 | DNA fragmentation factor subunit alpha | PRO_0000144716 | ||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||
| Domain | 17 – 96 | 80 | CIDE-N | |||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||
| Site | 117 – 118 | 2 | Cleavage; by caspase-3 | |||||||||||||||||||||||||
| Site | 224 – 225 | 2 | Cleavage; by caspase-3 | |||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||
| Modified residue | 1 | 1 | N-acetylmethionine Ref.15 | |||||||||||||||||||||||||
| Modified residue | 257 | 1 | Phosphoserine Ref.11 Ref.15 | |||||||||||||||||||||||||
| Modified residue | 310 | 1 | Phosphoserine Ref.12 Ref.15 | |||||||||||||||||||||||||
| Modified residue | 315 | 1 | Phosphoserine Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 | |||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||
| Alternative sequence | 262 – 268 | 7 | LVTKEDP → VGGNQGH in isoform DFF35. | VSP_001085 | ||||||||||||||||||||||||
| Alternative sequence | 269 – 331 | 63 | Missing in isoform DFF35. | VSP_001086 | ||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||
| Sequence conflict | 291 | 1 | R → W in AAH07721. Ref.7 | |||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||
| Helix | 39 – 50 | 12 | ||||||||||||||||||||||||||
| Beta strand | 60 – 64 | 5 | ||||||||||||||||||||||||||
| Helix | 73 – 78 | 6 | ||||||||||||||||||||||||||
| Beta strand | 84 – 88 | 5 | ||||||||||||||||||||||||||
| Helix | 239 – 246 | 8 | ||||||||||||||||||||||||||
| Turn | 251 – 254 | 4 | ||||||||||||||||||||||||||
| Helix | 257 – 264 | 8 | ||||||||||||||||||||||||||
| Helix | 268 – 274 | 7 | ||||||||||||||||||||||||||
| Helix | 279 – 297 | 19 | ||||||||||||||||||||||||||
| Helix | 298 – 300 | 3 | ||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis." Liu X., Zou H., Slaughter C., Wang X. Cell 89:175-184(1997) [PubMed: 9108473] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF45), PROTEIN SEQUENCE OF 171-181; 190-201; 214-218 AND 230-242. |
| [2] | "Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40." Gu J.J., Dong R.P., Zhang C., McLaughlin D.F., Wu M.X., Schlossman S.F. J. Biol. Chem. 274:20759-20762(1999) [PubMed: 10409614] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35). |
| [3] | "Identification of differentially expressed genes associated with HER-2/neu overexpression in human breast cancer cells." Oh J.J., Grosshans D.R., Wong S.G., Slamon D.J. Nucleic Acids Res. 27:4008-4017(1999) [PubMed: 10497265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35). |
| [4] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45). |
| [5] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45). Tissue: Eye, Kidney and Skeletal muscle. |
| [8] | Bienvenut W.V. Submitted (JAN-2010) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-16; 171-182; 190-201; 214-246; 249-269 AND 297-307, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Ovarian carcinoma. |
| [9] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Epithelium. |
| [10] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Epithelium. |
| [11] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, MASS SPECTROMETRY. |
| [12] | "Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-315, MASS SPECTROMETRY. |
| [13] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. |
| [14] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [15] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. |
| [16] | "Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45." Zhou P., Lugovskoy A.A., McCarty J.S., Li P., Wagner G. Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001) [PubMed: 11371636] [Abstract] Cited for: STRUCTURE BY NMR OF 11-100. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | U91985 mRNA. Translation: AAC51249.1. AF087573 mRNA. Translation: AAD32953.1. AF103799 mRNA. Translation: AAF02419.1. BT006980 mRNA. Translation: AAP35626.1. AL354956 Genomic DNA. Translation: CAI19197.1. CH471130 Genomic DNA. Translation: EAW71656.1. BC000037 mRNA. Translation: AAH00037.1. BC007112 mRNA. Translation: AAH07112.1. BC007721 mRNA. Translation: AAH07721.1. | ||||||||||||||||||||||||
| IPI | IPI00010882. IPI00604566. | ||||||||||||||||||||||||
| RefSeq | NP_004392.1. NP_998731.1. | ||||||||||||||||||||||||
| UniGene | Hs.484782 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||||||||
| DisProt | DP00173. | ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| IntAct | O00273. 19 interactions. | ||||||||||||||||||||||||
| STRING | O00273. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | O00273. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PeptideAtlas | O00273. | ||||||||||||||||||||||||
| PRIDE | O00273. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENST00000377038; ENSP00000366237; ENSG00000160049; Homo sapiens. [Genome view] | ||||||||||||||||||||||||
| GeneID | 1676. | ||||||||||||||||||||||||
| KEGG | hsa:1676. | ||||||||||||||||||||||||
| UCSC | uc001arj.1. human. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 1676. | ||||||||||||||||||||||||
| GeneCards | GC01M010454. | ||||||||||||||||||||||||
| H-InvDB | HIX0000115. | ||||||||||||||||||||||||
| HGNC | HGNC:2772. DFFA. | ||||||||||||||||||||||||
| HPA | CAB002679. HPA018859. HPA019938. HPA025230. | ||||||||||||||||||||||||
| MIM | 601882. gene. | ||||||||||||||||||||||||
| PharmGKB | PA27254. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| eggNOG | prNOG12550. | ||||||||||||||||||||||||
| HOGENOM | HBG716113. | ||||||||||||||||||||||||
| HOVERGEN | O00273. | ||||||||||||||||||||||||
| InParanoid | O00273. | ||||||||||||||||||||||||
| OMA | DGGTAWI. | ||||||||||||||||||||||||
| OrthoDB | EOG9TTK3D. | ||||||||||||||||||||||||
| PhylomeDB | O00273. | ||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||
| Pathway_Interaction_DB | caspase_pathway. Caspase cascade in apoptosis. faspathway. FAS signaling pathway (CD95). hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha. | ||||||||||||||||||||||||
| Reactome | REACT_578. Apoptosis. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | O00273. | ||||||||||||||||||||||||
| Bgee | O00273. | ||||||||||||||||||||||||
| CleanEx | HS_DFFA. | ||||||||||||||||||||||||
| Genevestigator | O00273. | ||||||||||||||||||||||||
| GermOnline | ENSG00000160049. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR003508. CAD. IPR015121. DNA_fragmentation_C. IPR017299. DNA_fragmentation_factor_asu. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF02017. CIDE-N. 1 hit. PF09033. DFF-C. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PIRSF | PIRSF037865. DFF_alpha. 1 hit. | ||||||||||||||||||||||||
| ProDom | PD316494. DNA_fragmentation_C. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||||||||
| SMART | SM00266. CAD. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS51135. CIDE_N. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 6896. | ||||||||||||||||||||||||
| PMAP-CutDB | O00273. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | DFFA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O00273 Secondary accession number(s): Q5T6G5, Q96I97, Q9Y6C6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


