Full text data of DFFA
DFFA
(DFF1, DFF45)
[Confidence: low (only semi-automatic identification from reviews)]
DNA fragmentation factor subunit alpha (DNA fragmentation factor 45 kDa subunit; DFF-45; Inhibitor of CAD; ICAD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
DNA fragmentation factor subunit alpha (DNA fragmentation factor 45 kDa subunit; DFF-45; Inhibitor of CAD; ICAD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O00273
ID DFFA_HUMAN Reviewed; 331 AA.
AC O00273; Q5T6G5; Q5T6G6; Q96I97; Q9Y6C6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=DNA fragmentation factor subunit alpha;
DE AltName: Full=DNA fragmentation factor 45 kDa subunit;
DE Short=DFF-45;
DE AltName: Full=Inhibitor of CAD;
DE Short=ICAD;
GN Name=DFFA; Synonyms=DFF1, DFF45; ORFNames=H13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF45), AND PROTEIN SEQUENCE OF
RP 171-181; 190-201; 214-218 AND 230-242.
RX PubMed=9108473; DOI=10.1016/S0092-8674(00)80197-X;
RA Liu X., Zou H., Slaughter C., Wang X.;
RT "DFF, a heterodimeric protein that functions downstream of caspase-3
RT to trigger DNA fragmentation during apoptosis.";
RL Cell 89:175-184(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35).
RX PubMed=10409614; DOI=10.1074/jbc.274.30.20759;
RA Gu J.J., Dong R.P., Zhang C., McLaughlin D.F., Wu M.X.,
RA Schlossman S.F.;
RT "Functional interaction of DFF35 and DFF45 with caspase-activated DNA
RT fragmentation nuclease DFF40.";
RL J. Biol. Chem. 274:20759-20762(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35).
RX PubMed=10497265; DOI=10.1093/nar/27.20.4008;
RA Oh J.J., Grosshans D.R., Wong S.G., Slamon D.J.;
RT "Identification of differentially expressed genes associated with HER-
RT 2/neu overexpression in human breast cancer cells.";
RL Nucleic Acids Res. 27:4008-4017(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RC TISSUE=Eye, Kidney, and Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-16; 171-182; 190-201; 214-246; 249-269 AND
RP 297-307, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP STRUCTURE BY NMR OF 11-100.
RX PubMed=11371636; DOI=10.1073/pnas.111145098;
RA Zhou P., Lugovskoy A.A., McCarty J.S., Li P., Wagner G.;
RT "Solution structure of DFF40 and DFF45 N-terminal domain complex and
RT mutual chaperone activity of DFF40 and DFF45.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001).
CC -!- FUNCTION: Inhibitor of the caspase-activated DNase (DFF40).
CC -!- SUBUNIT: Heterodimer of DFFA and DFFB.
CC -!- INTERACTION:
CC O54788:Dffb (xeno); NbExp=8; IntAct=EBI-727171, EBI-7365197;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=DFF45;
CC IsoId=O00273-1; Sequence=Displayed;
CC Name=DFF35;
CC IsoId=O00273-2; Sequence=VSP_001085, VSP_001086;
CC -!- PTM: Caspase-3 cleaves DFF45 at 2 sites to generate an active
CC factor.
CC -!- SIMILARITY: Contains 1 CIDE-N domain.
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DR EMBL; U91985; AAC51249.1; -; mRNA.
DR EMBL; AF087573; AAD32953.1; -; mRNA.
DR EMBL; AF103799; AAF02419.1; -; mRNA.
DR EMBL; BT006980; AAP35626.1; -; mRNA.
DR EMBL; AK313317; BAG36122.1; -; mRNA.
DR EMBL; AL354956; CAI19196.1; -; Genomic_DNA.
DR EMBL; AL354956; CAI19197.1; -; Genomic_DNA.
DR EMBL; CH471130; EAW71656.1; -; Genomic_DNA.
DR EMBL; CH471130; EAW71657.1; -; Genomic_DNA.
DR EMBL; BC000037; AAH00037.1; -; mRNA.
DR EMBL; BC007112; AAH07112.1; -; mRNA.
DR EMBL; BC007721; AAH07721.1; -; mRNA.
DR RefSeq; NP_004392.1; NM_004401.2.
DR RefSeq; NP_998731.1; NM_213566.1.
DR UniGene; Hs.484782; -.
DR PDB; 1IBX; NMR; -; B=11-100.
DR PDB; 1IYR; NMR; -; A=225-331.
DR PDB; 1KOY; NMR; -; A=239-300.
DR PDBsum; 1IBX; -.
DR PDBsum; 1IYR; -.
DR PDBsum; 1KOY; -.
DR DisProt; DP00173; -.
DR ProteinModelPortal; O00273; -.
DR SMR; O00273; 12-100, 225-306.
DR IntAct; O00273; 8.
DR MINT; MINT-365527; -.
DR STRING; 9606.ENSP00000366237; -.
DR PhosphoSite; O00273; -.
DR PaxDb; O00273; -.
DR PeptideAtlas; O00273; -.
DR PRIDE; O00273; -.
DR DNASU; 1676; -.
DR Ensembl; ENST00000377036; ENSP00000366235; ENSG00000160049.
DR Ensembl; ENST00000377038; ENSP00000366237; ENSG00000160049.
DR GeneID; 1676; -.
DR KEGG; hsa:1676; -.
DR UCSC; uc001arj.3; human.
DR CTD; 1676; -.
DR GeneCards; GC01M010516; -.
DR HGNC; HGNC:2772; DFFA.
DR HPA; CAB002679; -.
DR HPA; HPA018859; -.
DR HPA; HPA019938; -.
DR HPA; HPA025230; -.
DR MIM; 601882; gene.
DR neXtProt; NX_O00273; -.
DR PharmGKB; PA27254; -.
DR eggNOG; NOG40170; -.
DR HOGENOM; HOG000112204; -.
DR HOVERGEN; HBG000683; -.
DR InParanoid; O00273; -.
DR KO; K02310; -.
DR OMA; PCLLRRN; -.
DR OrthoDB; EOG7JQBP8; -.
DR PhylomeDB; O00273; -.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; O00273; -.
DR ChiTaRS; DFFA; human.
DR EvolutionaryTrace; O00273; -.
DR GeneWiki; DFFA; -.
DR GenomeRNAi; 1676; -.
DR NextBio; 6896; -.
DR PMAP-CutDB; Q5T6G5; -.
DR PRO; PR:O00273; -.
DR ArrayExpress; O00273; -.
DR Bgee; O00273; -.
DR CleanEx; HS_DFFA; -.
DR Genevestigator; O00273; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0004536; F:deoxyribonuclease activity; TAS:ProtInc.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR Gene3D; 1.10.1490.10; -; 1.
DR InterPro; IPR003508; CIDE-N_dom.
DR InterPro; IPR027296; DFF-C_dom.
DR InterPro; IPR017299; DNA_fragmentation_factor_asu.
DR InterPro; IPR015121; DNA_fragmentation_mid_dom.
DR Pfam; PF02017; CIDE-N; 1.
DR Pfam; PF09033; DFF-C; 1.
DR PIRSF; PIRSF037865; DFF_alpha; 1.
DR ProDom; PD316494; DNA_fragmentation_C; 1.
DR SMART; SM00266; CAD; 1.
DR PROSITE; PS51135; CIDE_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 331 DNA fragmentation factor subunit alpha.
FT /FTId=PRO_0000144716.
FT DOMAIN 17 96 CIDE-N.
FT SITE 117 118 Cleavage; by caspase-3.
FT SITE 224 225 Cleavage; by caspase-3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 315 315 Phosphoserine.
FT VAR_SEQ 262 268 LVTKEDP -> VGGNQGH (in isoform DFF35).
FT /FTId=VSP_001085.
FT VAR_SEQ 269 331 Missing (in isoform DFF35).
FT /FTId=VSP_001086.
FT CONFLICT 291 291 R -> W (in Ref. 8; AAH07721).
FT HELIX 39 50
FT STRAND 60 63
FT TURN 64 66
FT HELIX 73 78
FT STRAND 84 88
FT HELIX 239 246
FT TURN 251 254
FT HELIX 257 264
FT HELIX 268 274
FT HELIX 279 297
FT HELIX 298 300
SQ SEQUENCE 331 AA; 36522 MW; 8656FE45DB003DF3 CRC64;
MEVTGDAGVP ESGEIRTLKP CLLRRNYSRE QHGVAASCLE DLRSKACDIL AIDKSLTPVT
LVLAEDGTIV DDDDYFLCLP SNTKFVALAS NEKWAYNNSD GGTAWISQES FDVDETDSGA
GLKWKNVARQ LKEDLSSIIL LSEEDLQMLV DAPCSDLAQE LRQSCATVQR LQHTLQQVLD
QREEVRQSKQ LLQLYLQALE KEGSLLSKQE ESKAAFGEEV DAVDTGISRE TSSDVALASH
ILTALREKQA PELSLSSQDL ELVTKEDPKA LAVALNWDIK KTETVQEACE RELALRLQQT
QSLHSLRSIS ASKASPPGDL QNPKRARQDP T
//
ID DFFA_HUMAN Reviewed; 331 AA.
AC O00273; Q5T6G5; Q5T6G6; Q96I97; Q9Y6C6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=DNA fragmentation factor subunit alpha;
DE AltName: Full=DNA fragmentation factor 45 kDa subunit;
DE Short=DFF-45;
DE AltName: Full=Inhibitor of CAD;
DE Short=ICAD;
GN Name=DFFA; Synonyms=DFF1, DFF45; ORFNames=H13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF45), AND PROTEIN SEQUENCE OF
RP 171-181; 190-201; 214-218 AND 230-242.
RX PubMed=9108473; DOI=10.1016/S0092-8674(00)80197-X;
RA Liu X., Zou H., Slaughter C., Wang X.;
RT "DFF, a heterodimeric protein that functions downstream of caspase-3
RT to trigger DNA fragmentation during apoptosis.";
RL Cell 89:175-184(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35).
RX PubMed=10409614; DOI=10.1074/jbc.274.30.20759;
RA Gu J.J., Dong R.P., Zhang C., McLaughlin D.F., Wu M.X.,
RA Schlossman S.F.;
RT "Functional interaction of DFF35 and DFF45 with caspase-activated DNA
RT fragmentation nuclease DFF40.";
RL J. Biol. Chem. 274:20759-20762(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DFF35).
RX PubMed=10497265; DOI=10.1093/nar/27.20.4008;
RA Oh J.J., Grosshans D.R., Wong S.G., Slamon D.J.;
RT "Identification of differentially expressed genes associated with HER-
RT 2/neu overexpression in human breast cancer cells.";
RL Nucleic Acids Res. 27:4008-4017(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45).
RC TISSUE=Eye, Kidney, and Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-16; 171-182; 190-201; 214-246; 249-269 AND
RP 297-307, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP STRUCTURE BY NMR OF 11-100.
RX PubMed=11371636; DOI=10.1073/pnas.111145098;
RA Zhou P., Lugovskoy A.A., McCarty J.S., Li P., Wagner G.;
RT "Solution structure of DFF40 and DFF45 N-terminal domain complex and
RT mutual chaperone activity of DFF40 and DFF45.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001).
CC -!- FUNCTION: Inhibitor of the caspase-activated DNase (DFF40).
CC -!- SUBUNIT: Heterodimer of DFFA and DFFB.
CC -!- INTERACTION:
CC O54788:Dffb (xeno); NbExp=8; IntAct=EBI-727171, EBI-7365197;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=DFF45;
CC IsoId=O00273-1; Sequence=Displayed;
CC Name=DFF35;
CC IsoId=O00273-2; Sequence=VSP_001085, VSP_001086;
CC -!- PTM: Caspase-3 cleaves DFF45 at 2 sites to generate an active
CC factor.
CC -!- SIMILARITY: Contains 1 CIDE-N domain.
CC -----------------------------------------------------------------------
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DR EMBL; U91985; AAC51249.1; -; mRNA.
DR EMBL; AF087573; AAD32953.1; -; mRNA.
DR EMBL; AF103799; AAF02419.1; -; mRNA.
DR EMBL; BT006980; AAP35626.1; -; mRNA.
DR EMBL; AK313317; BAG36122.1; -; mRNA.
DR EMBL; AL354956; CAI19196.1; -; Genomic_DNA.
DR EMBL; AL354956; CAI19197.1; -; Genomic_DNA.
DR EMBL; CH471130; EAW71656.1; -; Genomic_DNA.
DR EMBL; CH471130; EAW71657.1; -; Genomic_DNA.
DR EMBL; BC000037; AAH00037.1; -; mRNA.
DR EMBL; BC007112; AAH07112.1; -; mRNA.
DR EMBL; BC007721; AAH07721.1; -; mRNA.
DR RefSeq; NP_004392.1; NM_004401.2.
DR RefSeq; NP_998731.1; NM_213566.1.
DR UniGene; Hs.484782; -.
DR PDB; 1IBX; NMR; -; B=11-100.
DR PDB; 1IYR; NMR; -; A=225-331.
DR PDB; 1KOY; NMR; -; A=239-300.
DR PDBsum; 1IBX; -.
DR PDBsum; 1IYR; -.
DR PDBsum; 1KOY; -.
DR DisProt; DP00173; -.
DR ProteinModelPortal; O00273; -.
DR SMR; O00273; 12-100, 225-306.
DR IntAct; O00273; 8.
DR MINT; MINT-365527; -.
DR STRING; 9606.ENSP00000366237; -.
DR PhosphoSite; O00273; -.
DR PaxDb; O00273; -.
DR PeptideAtlas; O00273; -.
DR PRIDE; O00273; -.
DR DNASU; 1676; -.
DR Ensembl; ENST00000377036; ENSP00000366235; ENSG00000160049.
DR Ensembl; ENST00000377038; ENSP00000366237; ENSG00000160049.
DR GeneID; 1676; -.
DR KEGG; hsa:1676; -.
DR UCSC; uc001arj.3; human.
DR CTD; 1676; -.
DR GeneCards; GC01M010516; -.
DR HGNC; HGNC:2772; DFFA.
DR HPA; CAB002679; -.
DR HPA; HPA018859; -.
DR HPA; HPA019938; -.
DR HPA; HPA025230; -.
DR MIM; 601882; gene.
DR neXtProt; NX_O00273; -.
DR PharmGKB; PA27254; -.
DR eggNOG; NOG40170; -.
DR HOGENOM; HOG000112204; -.
DR HOVERGEN; HBG000683; -.
DR InParanoid; O00273; -.
DR KO; K02310; -.
DR OMA; PCLLRRN; -.
DR OrthoDB; EOG7JQBP8; -.
DR PhylomeDB; O00273; -.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; O00273; -.
DR ChiTaRS; DFFA; human.
DR EvolutionaryTrace; O00273; -.
DR GeneWiki; DFFA; -.
DR GenomeRNAi; 1676; -.
DR NextBio; 6896; -.
DR PMAP-CutDB; Q5T6G5; -.
DR PRO; PR:O00273; -.
DR ArrayExpress; O00273; -.
DR Bgee; O00273; -.
DR CleanEx; HS_DFFA; -.
DR Genevestigator; O00273; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0004536; F:deoxyribonuclease activity; TAS:ProtInc.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR Gene3D; 1.10.1490.10; -; 1.
DR InterPro; IPR003508; CIDE-N_dom.
DR InterPro; IPR027296; DFF-C_dom.
DR InterPro; IPR017299; DNA_fragmentation_factor_asu.
DR InterPro; IPR015121; DNA_fragmentation_mid_dom.
DR Pfam; PF02017; CIDE-N; 1.
DR Pfam; PF09033; DFF-C; 1.
DR PIRSF; PIRSF037865; DFF_alpha; 1.
DR ProDom; PD316494; DNA_fragmentation_C; 1.
DR SMART; SM00266; CAD; 1.
DR PROSITE; PS51135; CIDE_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 331 DNA fragmentation factor subunit alpha.
FT /FTId=PRO_0000144716.
FT DOMAIN 17 96 CIDE-N.
FT SITE 117 118 Cleavage; by caspase-3.
FT SITE 224 225 Cleavage; by caspase-3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 315 315 Phosphoserine.
FT VAR_SEQ 262 268 LVTKEDP -> VGGNQGH (in isoform DFF35).
FT /FTId=VSP_001085.
FT VAR_SEQ 269 331 Missing (in isoform DFF35).
FT /FTId=VSP_001086.
FT CONFLICT 291 291 R -> W (in Ref. 8; AAH07721).
FT HELIX 39 50
FT STRAND 60 63
FT TURN 64 66
FT HELIX 73 78
FT STRAND 84 88
FT HELIX 239 246
FT TURN 251 254
FT HELIX 257 264
FT HELIX 268 274
FT HELIX 279 297
FT HELIX 298 300
SQ SEQUENCE 331 AA; 36522 MW; 8656FE45DB003DF3 CRC64;
MEVTGDAGVP ESGEIRTLKP CLLRRNYSRE QHGVAASCLE DLRSKACDIL AIDKSLTPVT
LVLAEDGTIV DDDDYFLCLP SNTKFVALAS NEKWAYNNSD GGTAWISQES FDVDETDSGA
GLKWKNVARQ LKEDLSSIIL LSEEDLQMLV DAPCSDLAQE LRQSCATVQR LQHTLQQVLD
QREEVRQSKQ LLQLYLQALE KEGSLLSKQE ESKAAFGEEV DAVDTGISRE TSSDVALASH
ILTALREKQA PELSLSSQDL ELVTKEDPKA LAVALNWDIK KTETVQEACE RELALRLQQT
QSLHSLRSIS ASKASPPGDL QNPKRARQDP T
//
MIM
601882
*RECORD*
*FIELD* NO
601882
*FIELD* TI
*601882 DNA FRAGMENTATION FACTOR, 45-KD, ALPHA SUBUNIT; DFFA
;;DFF1;;
DFF45;;
INHIBITOR OF CASPASE-ACTIVATED DNase; ICAD
read more*FIELD* TX
CLONING
Liu et al. (1997) identified and purified from HeLa cytosol a protein
that induces DNA fragmentation in coincubated nuclei after it is
activated by caspase-3 (600636). This protein, designated DNA
fragmentation factor (DFF) by them, was found to be a heterodimer of
40-kD (DFFB; 601883) and 45-kD (DFFA) subunits. Amino acid sequence of
the HeLa cell 45-kD subunit, determined from its cDNA sequence, showed
that it is a novel protein.
GENE FUNCTION
Liu et al. (1997) determined that caspase-3 cleaves the 45-kD subunit at
2 sites to generate an active factor that produces DNA fragmentation
without further requirement of caspase-3 or other cytosolic proteins. In
cells undergoing apoptosis, the 45-kD subunit was cleaved in the same
pattern as it is cleaved by caspase-3 in vitro. These results delineated
a direct signal transduction pathway during apoptosis: caspase-3 to DFF
to DNA fragmentation.
Inohara et al. (1998) reported the identification and characterization
of 2 mammalian genes, which they called CIDEA (604440) and CIDEB
(604441) (cell death-inducing DFFA-like effectors A and B), encoding
highly related proteins with homology to the N-terminal region of DFF45.
CIDEA and CIDEB were found to activate apoptosis in mammalian cells, and
this was inhibited by DFF45 but not by caspase inhibitors. Expression of
CIDEA induced DNA fragmentation in 293T cells, and this was also
inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic
activities of CIDEs. In addition to mammalian CIDEA and CIDEB, Inohara
et al. (1998) identified DREP1, a Drosophila homolog of DFF45 that could
inhibit CIDEA-mediated apoptosis. Mutant analysis revealed that the
C-terminal region of CIDEA was necessary and sufficient for killing,
whereas the region with homology to DFF45 located in the N terminus was
required for DFF45 to inhibit CIDEA-induced apoptosis. CD95/Fas
(134637)-mediated apoptosis was enhanced by CIDEs but inhibited by
DFF45. These studies suggested that DFF45 is evolutionarily conserved
and implicated CIDEs as DFF45-inhibitable effectors that promote cell
death and DNA fragmentation.
GENE STRUCTURE
By in silico analysis, Abel et al. (2002) determined that the DFFA gene
contains 6 exons that span approximately 11 kb of genomic DNA.
MAPPING
Leek et al. (1997) mapped the DFFA gene to 1p36.3-p36.2 by fluorescence
in situ hybridization.
MOLECULAR GENETICS
Abel et al. (2002) presented evidence that the DFFA gene is located in
the smallest region of deletion overlap in Scandinavian neuroblastoma
tumors (see 256700). They performed genomic sequence analysis of DFFA
and caspase-9 (602234) in 44 primary neuroblastoma tumors and in 2
detected a rare allelic variant in the DFFA gene, i.e., a 206T-C
transition in exon 2, resulting in a nonpolar-to-polar substitution
(ile69 to thr; I60T) in a preserved hydrophobic patch of the protein.
The variant was present in hemizygous form due to deletion of the more
common allele of this polymorphism in 1 tumor and was present in
heterozygous form in the other. Only 1 of 194 normal control alleles was
found to carry this variant; thus, none of 97 healthy control
individuals was homozygous. Moreover, RT-PCR expression studies showed
that the DFFA gene was expressed in low-stage neuroblastoma tumors and
to a lesser degree in high-stage neuroblastomas.
*FIELD* RF
1. Abel, F.; Sjoberg, R.-M.; Ejeskar, K.; Krona, C.; Martinsson, T.
: Analyses of apoptotic regulators CASP9 and DFFA at 1p36.2, reveal
rare allele variants in human neuroblastoma tumours. Brit. J. Cancer 86:
596-604, 2002.
2. Inohara, N.; Koseki, T.; Chen, S.; Wu, X.; Nunez, G.: CIDE, a
novel family of cell death activators with homology to the 45 kDa
subunit of the DNA fragmentation factor. EMBO J. 17: 2526-2533,
1998.
3. Leek, J. P.; Carr, I. M.; Bell, S. M.; Markham, A. F.; Lench, N.
J.: Assignment of the DNA fragmentation factor gene (DFFA) to human
chromosome bands 1p36.3-p36.2 by in situ hybridization. Cytogenet.
Cell Genet. 79: 212-213, 1997.
4. Liu, X.; Zou, H.; Slaughter, C.; Wang, X.: DFF, a heterodimeric
protein that functions downstream of caspase-3 to trigger DNA fragmentation
during apoptosis. Cell 89: 175-184, 1997.
*FIELD* CN
Victor A. McKusick - updated: 5/16/2003
Stylianos E. Antonarakis - updated: 1/19/2000
Victor A. McKusick - updated: 5/28/1998
*FIELD* CD
Victor A. McKusick: 6/20/1997
*FIELD* ED
carol: 06/03/2003
tkritzer: 5/28/2003
terry: 5/16/2003
mgross: 1/9/2003
mgross: 1/19/2000
terry: 6/1/1998
terry: 5/28/1998
mark: 11/5/1997
terry: 6/23/1997
alopez: 6/20/1997
*RECORD*
*FIELD* NO
601882
*FIELD* TI
*601882 DNA FRAGMENTATION FACTOR, 45-KD, ALPHA SUBUNIT; DFFA
;;DFF1;;
DFF45;;
INHIBITOR OF CASPASE-ACTIVATED DNase; ICAD
read more*FIELD* TX
CLONING
Liu et al. (1997) identified and purified from HeLa cytosol a protein
that induces DNA fragmentation in coincubated nuclei after it is
activated by caspase-3 (600636). This protein, designated DNA
fragmentation factor (DFF) by them, was found to be a heterodimer of
40-kD (DFFB; 601883) and 45-kD (DFFA) subunits. Amino acid sequence of
the HeLa cell 45-kD subunit, determined from its cDNA sequence, showed
that it is a novel protein.
GENE FUNCTION
Liu et al. (1997) determined that caspase-3 cleaves the 45-kD subunit at
2 sites to generate an active factor that produces DNA fragmentation
without further requirement of caspase-3 or other cytosolic proteins. In
cells undergoing apoptosis, the 45-kD subunit was cleaved in the same
pattern as it is cleaved by caspase-3 in vitro. These results delineated
a direct signal transduction pathway during apoptosis: caspase-3 to DFF
to DNA fragmentation.
Inohara et al. (1998) reported the identification and characterization
of 2 mammalian genes, which they called CIDEA (604440) and CIDEB
(604441) (cell death-inducing DFFA-like effectors A and B), encoding
highly related proteins with homology to the N-terminal region of DFF45.
CIDEA and CIDEB were found to activate apoptosis in mammalian cells, and
this was inhibited by DFF45 but not by caspase inhibitors. Expression of
CIDEA induced DNA fragmentation in 293T cells, and this was also
inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic
activities of CIDEs. In addition to mammalian CIDEA and CIDEB, Inohara
et al. (1998) identified DREP1, a Drosophila homolog of DFF45 that could
inhibit CIDEA-mediated apoptosis. Mutant analysis revealed that the
C-terminal region of CIDEA was necessary and sufficient for killing,
whereas the region with homology to DFF45 located in the N terminus was
required for DFF45 to inhibit CIDEA-induced apoptosis. CD95/Fas
(134637)-mediated apoptosis was enhanced by CIDEs but inhibited by
DFF45. These studies suggested that DFF45 is evolutionarily conserved
and implicated CIDEs as DFF45-inhibitable effectors that promote cell
death and DNA fragmentation.
GENE STRUCTURE
By in silico analysis, Abel et al. (2002) determined that the DFFA gene
contains 6 exons that span approximately 11 kb of genomic DNA.
MAPPING
Leek et al. (1997) mapped the DFFA gene to 1p36.3-p36.2 by fluorescence
in situ hybridization.
MOLECULAR GENETICS
Abel et al. (2002) presented evidence that the DFFA gene is located in
the smallest region of deletion overlap in Scandinavian neuroblastoma
tumors (see 256700). They performed genomic sequence analysis of DFFA
and caspase-9 (602234) in 44 primary neuroblastoma tumors and in 2
detected a rare allelic variant in the DFFA gene, i.e., a 206T-C
transition in exon 2, resulting in a nonpolar-to-polar substitution
(ile69 to thr; I60T) in a preserved hydrophobic patch of the protein.
The variant was present in hemizygous form due to deletion of the more
common allele of this polymorphism in 1 tumor and was present in
heterozygous form in the other. Only 1 of 194 normal control alleles was
found to carry this variant; thus, none of 97 healthy control
individuals was homozygous. Moreover, RT-PCR expression studies showed
that the DFFA gene was expressed in low-stage neuroblastoma tumors and
to a lesser degree in high-stage neuroblastomas.
*FIELD* RF
1. Abel, F.; Sjoberg, R.-M.; Ejeskar, K.; Krona, C.; Martinsson, T.
: Analyses of apoptotic regulators CASP9 and DFFA at 1p36.2, reveal
rare allele variants in human neuroblastoma tumours. Brit. J. Cancer 86:
596-604, 2002.
2. Inohara, N.; Koseki, T.; Chen, S.; Wu, X.; Nunez, G.: CIDE, a
novel family of cell death activators with homology to the 45 kDa
subunit of the DNA fragmentation factor. EMBO J. 17: 2526-2533,
1998.
3. Leek, J. P.; Carr, I. M.; Bell, S. M.; Markham, A. F.; Lench, N.
J.: Assignment of the DNA fragmentation factor gene (DFFA) to human
chromosome bands 1p36.3-p36.2 by in situ hybridization. Cytogenet.
Cell Genet. 79: 212-213, 1997.
4. Liu, X.; Zou, H.; Slaughter, C.; Wang, X.: DFF, a heterodimeric
protein that functions downstream of caspase-3 to trigger DNA fragmentation
during apoptosis. Cell 89: 175-184, 1997.
*FIELD* CN
Victor A. McKusick - updated: 5/16/2003
Stylianos E. Antonarakis - updated: 1/19/2000
Victor A. McKusick - updated: 5/28/1998
*FIELD* CD
Victor A. McKusick: 6/20/1997
*FIELD* ED
carol: 06/03/2003
tkritzer: 5/28/2003
terry: 5/16/2003
mgross: 1/9/2003
mgross: 1/19/2000
terry: 6/1/1998
terry: 5/28/1998
mark: 11/5/1997
terry: 6/23/1997
alopez: 6/20/1997