DFFB_HUMAN
ID DFFB_HUMAN Reviewed; 338 AA.
AC O76075; O60521; Q5SR22; Q9BYI4; Q9BYI5; Q9BYI6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=DNA fragmentation factor subunit beta;
DE EC=3.-.-.-;
DE AltName: Full=Caspase-activated deoxyribonuclease;
DE Short=CAD;
DE Short=Caspase-activated DNase;
DE AltName: Full=Caspase-activated nuclease;
DE Short=CPAN;
DE AltName: Full=DNA fragmentation factor 40 kDa subunit;
DE Short=DFF-40;
GN Name=DFFB; Synonyms=CAD, DFF2, DFF40;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RX PubMed=9671700; DOI=10.1073/pnas.95.15.8461;
RA Liu X., Li P., Widlak P., Zou H., Luo X., Garrard W.T., Wang X.;
RT "The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation
RT and chromatin condensation during apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8461-8466(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RX PubMed=9689044; DOI=10.1073/pnas.95.16.9123;
RA Mukae N., Enari M., Sakahira H., Fukuda Y., Inazawa J., Toh H., Nagata S.;
RT "Molecular cloning and characterization of human caspase-activated DNase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9123-9128(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RC TISSUE=Pancreas;
RX PubMed=9560346; DOI=10.1016/s0960-9822(98)79298-x;
RA Halenbeck R., MacDonald H., Roulston A., Chen T.T., Conroy L.,
RA Williams L.T.;
RT "CPAN, a human nuclease regulated by the caspase-sensitive inhibitor
RT DFF45.";
RL Curr. Biol. 8:537-540(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA; GAMMA AND DELTA).
RC TISSUE=Fetal brain;
RA Nakagawara A., Takahashi M., Takada N., Kawamoto T.;
RT "DFF40 delta.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 MRNA] (ISOFORM ALPHA).
RC TISSUE=Lung;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [9]
RP INTERACTION WITH H1-1.
RX PubMed=19882353; DOI=10.1007/s10495-009-0418-7;
RA Ninios Y.P., Sekeri-Pataryas K.E., Sourlingas T.G.;
RT "Histone H1 subtype preferences of DFF40 and possible nuclear localization
RT of DFF40/45 in normal and trichostatin A-treated NB4 leukemic cells.";
RL Apoptosis 15:128-138(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11] {ECO:0007744|PDB:1IBX}
RP STRUCTURE BY NMR OF 1-80, AND SUBUNIT.
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 mutual
RT chaperone activity of DFF40 and DFF45.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001).
RN [12]
RP VARIANT LYS-196.
RX PubMed=10830907; DOI=10.1007/s004390000257;
RA Judson H., van Roy N., Strain L., Vandesompele J., Van Gele M.,
RA Speleman F., Bonthron D.T.;
RT "Structure and mutation analysis of the gene encoding DNA fragmentation
RT factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour
RT suppressor gene.";
RL Hum. Genet. 106:406-413(2000).
CC -!- FUNCTION: Nuclease that induces DNA fragmentation and chromatin
CC condensation during apoptosis. Degrades naked DNA and induces apoptotic
CC morphology.
CC -!- ACTIVITY REGULATION: Inhibited by DFFA (DFF45).
CC -!- SUBUNIT: Heterodimer of DFFA and DFFB (PubMed:11371636). Interacts with
CC H1-1 (PubMed:19882353). {ECO:0000269|PubMed:11371636,
CC ECO:0000269|PubMed:19882353}.
CC -!- INTERACTION:
CC O76075; O00273: DFFA; NbExp=5; IntAct=EBI-1053821, EBI-727171;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Alpha;
CC IsoId=O76075-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=O76075-2; Sequence=VSP_001080;
CC Name=Gamma;
CC IsoId=O76075-3; Sequence=VSP_001081, VSP_001082;
CC Name=Delta;
CC IsoId=O76075-4; Sequence=VSP_001083, VSP_001084;
CC -!- MISCELLANEOUS: [Isoform Beta]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Gamma]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Delta]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF064019; AAC39920.1; -; mRNA.
DR EMBL; AB013918; BAA32250.1; -; mRNA.
DR EMBL; AF039210; AAC39709.1; -; mRNA.
DR EMBL; AB028911; BAB40447.1; -; mRNA.
DR EMBL; AB028912; BAB40448.1; -; mRNA.
DR EMBL; AB028913; BAB40449.1; -; mRNA.
DR EMBL; AK290877; BAF83566.1; -; mRNA.
DR EMBL; AL691523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048797; AAH48797.1; -; mRNA.
DR CCDS; CCDS52.1; -. [O76075-1]
DR RefSeq; NP_001307061.1; NM_001320132.1.
DR RefSeq; NP_004393.1; NM_004402.3. [O76075-1]
DR PDB; 1IBX; NMR; -; A=1-80.
DR PDBsum; 1IBX; -.
DR AlphaFoldDB; O76075; -.
DR SMR; O76075; -.
DR BioGRID; 108041; 26.
DR ComplexPortal; CPX-2498; DNA fragmentation factor complex.
DR IntAct; O76075; 16.
DR MINT; O76075; -.
DR STRING; 9606.ENSP00000339524; -.
DR iPTMnet; O76075; -.
DR PhosphoSitePlus; O76075; -.
DR BioMuta; DFFB; -.
DR EPD; O76075; -.
DR jPOST; O76075; -.
DR MassIVE; O76075; -.
DR MaxQB; O76075; -.
DR PaxDb; O76075; -.
DR PeptideAtlas; O76075; -.
DR PRIDE; O76075; -.
DR ProteomicsDB; 50376; -. [O76075-1]
DR ProteomicsDB; 50377; -. [O76075-2]
DR ProteomicsDB; 50378; -. [O76075-3]
DR ProteomicsDB; 50379; -. [O76075-4]
DR Antibodypedia; 3813; 540 antibodies from 37 providers.
DR DNASU; 1677; -.
DR Ensembl; ENST00000339350.7; ENSP00000343218.3; ENSG00000169598.17. [O76075-3]
DR Ensembl; ENST00000378209.8; ENSP00000367454.4; ENSG00000169598.17. [O76075-1]
DR Ensembl; ENST00000491998.5; ENSP00000436775.1; ENSG00000169598.17. [O76075-2]
DR GeneID; 1677; -.
DR KEGG; hsa:1677; -.
DR MANE-Select; ENST00000378209.8; ENSP00000367454.4; NM_004402.4; NP_004393.1.
DR UCSC; uc001alc.5; human. [O76075-1]
DR CTD; 1677; -.
DR DisGeNET; 1677; -.
DR GeneCards; DFFB; -.
DR HGNC; HGNC:2773; DFFB.
DR HPA; ENSG00000169598; Tissue enhanced (intestine).
DR MIM; 601883; gene.
DR neXtProt; NX_O76075; -.
DR OpenTargets; ENSG00000169598; -.
DR PharmGKB; PA27255; -.
DR VEuPathDB; HostDB:ENSG00000169598; -.
DR eggNOG; ENOG502R0RF; Eukaryota.
DR GeneTree; ENSGT00390000014490; -.
DR HOGENOM; CLU_049235_1_1_1; -.
DR InParanoid; O76075; -.
DR OMA; AQYHGSY; -.
DR PhylomeDB; O76075; -.
DR TreeFam; TF102022; -.
DR PathwayCommons; O76075; -.
DR Reactome; R-HSA-140342; Apoptosis induced DNA fragmentation.
DR SignaLink; O76075; -.
DR SIGNOR; O76075; -.
DR BioGRID-ORCS; 1677; 19 hits in 1079 CRISPR screens.
DR ChiTaRS; DFFB; human.
DR EvolutionaryTrace; O76075; -.
DR GeneWiki; DFFB; -.
DR GenomeRNAi; 1677; -.
DR Pharos; O76075; Tbio.
DR PRO; PR:O76075; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O76075; protein.
DR Bgee; ENSG00000169598; Expressed in cerebellar hemisphere and 142 other tissues.
DR ExpressionAtlas; O76075; baseline and differential.
DR Genevisible; O76075; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0004536; F:deoxyribonuclease activity; IMP:CAFA.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:CAFA.
DR GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR GO; GO:0030263; P:apoptotic chromosome condensation; IDA:UniProtKB.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:CAFA.
DR GO; GO:0006308; P:DNA catabolic process; IMP:CAFA.
DR GO; GO:1902511; P:negative regulation of apoptotic DNA fragmentation; IDA:ComplexPortal.
DR InterPro; IPR003508; CIDE-N_dom.
DR InterPro; IPR039729; DFF40.
DR InterPro; IPR015311; DFF40_C.
DR InterPro; IPR044925; His-Me_finger_sf.
DR PANTHER; PTHR13067; PTHR13067; 1.
DR Pfam; PF02017; CIDE-N; 1.
DR Pfam; PF09230; DFF40; 1.
DR SMART; SM00266; CAD; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
DR PROSITE; PS51135; CIDE_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Hydrolase;
KW Nuclease; Nucleus; Reference proteome.
FT CHAIN 1..338
FT /note="DNA fragmentation factor subunit beta"
FT /id="PRO_0000144713"
FT DOMAIN 4..80
FT /note="CIDE-N"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00447"
FT VAR_SEQ 81..116
FT /note="YVSDIRRFLSAFHEPQVGLIQAAQQLLCDEQAPQRQ -> SVGVRARTKTRD
FT TSSLSPGDCQALGNGGRCGQRLFL (in isoform Gamma)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_001081"
FT VAR_SEQ 81..103
FT /note="YVSDIRRFLSAFHEPQVGLIQAA -> WFCHVSQDSLTLLGSSCPPALVS
FT (in isoform Delta)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_001083"
FT VAR_SEQ 104..338
FT /note="Missing (in isoform Delta)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_001084"
FT VAR_SEQ 117..338
FT /note="Missing (in isoform Gamma)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_001082"
FT VAR_SEQ 262..338
FT /note="IEKKRTIIPTLVEAIKEQDGREVDWEYFYGLLFTSENLKLVHIVCHKKTTHK
FT LNCDPSRIYKPQTRLKRKQPVRKRQ -> DGVLLCGPG (in isoform Beta)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_001080"
FT VARIANT 196
FT /note="R -> K (in dbSNP:rs12738235)"
FT /evidence="ECO:0000269|PubMed:10830907"
FT /id="VAR_009305"
FT VARIANT 277
FT /note="K -> R (in dbSNP:rs12564400)"
FT /id="VAR_048737"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:1IBX"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:1IBX"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:1IBX"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1IBX"
FT STRAND 44..51
FT /evidence="ECO:0007829|PDB:1IBX"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1IBX"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:1IBX"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:1IBX"
SQ SEQUENCE 338 AA; 39110 MW; 0B0F3F8D91209389 CRC64;
MLQKPKSVKL RALRSPRKFG VAGRSCQEVL RKGCLRFQLP ERGSRLCLYE DGTELTEDYF
PSVPDNAELV LLTLGQAWQG YVSDIRRFLS AFHEPQVGLI QAAQQLLCDE QAPQRQRLLA
DLLHNVSQNI AAETRAEDPP WFEGLESRFQ SKSGYLRYSC ESRIRSYLRE VSSYPSTVGA
EAQEEFLRVL GSMCQRLRSM QYNGSYFDRG AKGGSRLCTP EGWFSCQGPF DMDSCLSRHS
INPYSNRESR ILFSTWNLDH IIEKKRTIIP TLVEAIKEQD GREVDWEYFY GLLFTSENLK
LVHIVCHKKT THKLNCDPSR IYKPQTRLKR KQPVRKRQ
