DFFA_MOUSE
ID DFFA_MOUSE Reviewed; 331 AA.
AC O54786; B2KFX0; O54787; Q8BQC7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 176.
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=Icad;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9422506; DOI=10.1038/34112;
RA Enari M., Sakahira H., Yokoyama H., Okawa K., Iwamatsu A., Nagata S.;
RT "A caspase-activated DNase that degrades DNA during apoptosis, and its
RT inhibitor ICAD.";
RL Nature 391:43-50(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9422513; DOI=10.1038/34214;
RA Sakahira H., Enari M., Nagata S.;
RT "Cleavage of CAD inhibitor in CAD activation and DNA degradation during
RT apoptosis.";
RL Nature 391:96-99(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Inhibitor of the caspase-activated DNase (DFF40).
CC -!- SUBUNIT: Heterodimer of DFFA and DFFB. {ECO:0000250|UniProtKB:O00273}.
CC -!- INTERACTION:
CC O54786; O54788: Dffb; NbExp=7; IntAct=EBI-1634519, EBI-7365197;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=ICAD-L;
CC IsoId=O54786-1; Sequence=Displayed;
CC Name=ICAD-S;
CC IsoId=O54786-2; Sequence=VSP_001087, VSP_001088;
CC -!- PTM: Caspase-3 cleaves DFF45 at 2 sites to generate an active factor.
CC {ECO:0000250}.
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DR EMBL; AB009375; BAA24140.1; -; mRNA.
DR EMBL; AB009376; BAA24141.1; -; mRNA.
DR EMBL; AK051011; BAC34496.1; -; mRNA.
DR EMBL; AL611967; CAM13988.1; -; Genomic_DNA.
DR EMBL; CU210839; CAQ52098.1; -; Genomic_DNA.
DR CCDS; CCDS18951.1; -. [O54786-1]
DR CCDS; CCDS18952.1; -. [O54786-2]
DR RefSeq; NP_001020467.1; NM_001025296.2. [O54786-1]
DR PDB; 1F2R; NMR; -; I=1-100.
DR PDBsum; 1F2R; -.
DR AlphaFoldDB; O54786; -.
DR SMR; O54786; -.
DR BioGRID; 199211; 17.
DR IntAct; O54786; 4.
DR MINT; O54786; -.
DR STRING; 10090.ENSMUSP00000030816; -.
DR iPTMnet; O54786; -.
DR PhosphoSitePlus; O54786; -.
DR EPD; O54786; -.
DR jPOST; O54786; -.
DR MaxQB; O54786; -.
DR PaxDb; O54786; -.
DR PeptideAtlas; O54786; -.
DR PRIDE; O54786; -.
DR ProteomicsDB; 279409; -. [O54786-1]
DR ProteomicsDB; 279410; -. [O54786-2]
DR Antibodypedia; 3633; 854 antibodies from 46 providers.
DR DNASU; 13347; -.
DR Ensembl; ENSMUST00000030816; ENSMUSP00000030816; ENSMUSG00000028974. [O54786-1]
DR Ensembl; ENSMUST00000103216; ENSMUSP00000099505; ENSMUSG00000028974. [O54786-2]
DR GeneID; 13347; -.
DR KEGG; mmu:13347; -.
DR UCSC; uc008vvr.2; mouse. [O54786-1]
DR CTD; 1676; -.
DR MGI; MGI:1196227; Dffa.
DR VEuPathDB; HostDB:ENSMUSG00000028974; -.
DR eggNOG; ENOG502RQ19; Eukaryota.
DR GeneTree; ENSGT00390000018596; -.
DR HOGENOM; CLU_086234_0_0_1; -.
DR InParanoid; O54786; -.
DR OMA; WMARESV; -.
DR OrthoDB; 1564672at2759; -.
DR PhylomeDB; O54786; -.
DR TreeFam; TF102021; -.
DR Reactome; R-MMU-140342; Apoptosis induced DNA fragmentation.
DR BioGRID-ORCS; 13347; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Dffa; mouse.
DR EvolutionaryTrace; O54786; -.
DR PRO; PR:O54786; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; O54786; protein.
DR Bgee; ENSMUSG00000028974; Expressed in soleus muscle and 113 other tissues.
DR ExpressionAtlas; O54786; baseline and differential.
DR Genevisible; O54786; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0060703; F:deoxyribonuclease inhibitor activity; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044183; F:protein folding chaperone; ISO:MGI.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IEA:InterPro.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISO:MGI.
DR GO; GO:1902511; P:negative regulation of apoptotic DNA fragmentation; IMP:MGI.
DR GO; GO:0032076; P:negative regulation of deoxyribonuclease activity; ISO:MGI.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0070242; P:thymocyte apoptotic process; IMP:MGI.
DR InterPro; IPR003508; CIDE-N_dom.
DR InterPro; IPR027296; DFF-C.
DR InterPro; IPR017299; DFF45.
DR InterPro; IPR015121; DNA_fragmentation_mid_dom.
DR PANTHER; PTHR12306:SF16; PTHR12306:SF16; 1.
DR Pfam; PF02017; CIDE-N; 1.
DR Pfam; PF09033; DFF-C; 1.
DR PIRSF; PIRSF037865; DFF_alpha; 1.
DR SMART; SM00266; CAD; 1.
DR SUPFAM; SSF81783; SSF81783; 1.
DR PROSITE; PS51135; CIDE_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cytoplasm;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..331
FT /note="DNA fragmentation factor subunit alpha"
FT /id="PRO_0000144717"
FT DOMAIN 17..96
FT /note="CIDE-N"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00447"
FT REGION 306..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 117..118
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT SITE 224..225
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O00273"
FT MOD_RES 243
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00273"
FT VAR_SEQ 262..265
FT /note="SVSK -> VGKN (in isoform ICAD-S)"
FT /evidence="ECO:0000305"
FT /id="VSP_001087"
FT VAR_SEQ 266..331
FT /note="Missing (in isoform ICAD-S)"
FT /evidence="ECO:0000305"
FT /id="VSP_001088"
FT CONFLICT 95
FT /note="I -> T (in Ref. 1; BAA24140, 2; BAA24141 and 4;
FT CAQ52098)"
FT /evidence="ECO:0000305"
FT STRAND 6..11
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 28..38
FT /evidence="ECO:0007829|PDB:1F2R"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:1F2R"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:1F2R"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:1F2R"
SQ SEQUENCE 331 AA; 36572 MW; 4EA9314DD470040F CRC64;
MELSRGASAP DPDDVRPLKP CLLRRNHSRD QHGVAASSLE ELRSKACELL AIDKSLTPIT
LVLAEDGTIV DDDDYFLCLP SNTKFVALAC NEKWIYNDSD GGTAWVSQES FEADEPDSRA
GVKWKNVARQ LKEDLSSIIL LSEEDLQALI DIPCAELAQE LCQSCATVQG LQSTLQQVLD
QREEARQSKQ LLELYLQALE KEGNILSNQK ESKAALSEEL DAVDTGVGRE MASEVLLRSQ
ILTTLKEKPA PELSLSSQDL ESVSKEDPKA LAVALSWDIR KAETVQQACT TELALRLQQV
QSLHSLRNLS ARRSPLPGEP QRPKRAKRDS S
