Reviewed, UniProtKB/Swiss-Prot O00273 (DFFA_HUMAN)

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

Name:	DFFA
Synonyms:	DFF1, DFF45
ORF Names:	H13

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	Cytoplasm.
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.1 Traceable author statement. Source: ProtInc negative regulation of apoptosis Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.1 Inferred from Experiment. Source: Reactome nucleoplasm Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	caspase-activated deoxyribonuclease activity Ref.1 Traceable author statement. Source: ProtInc identical protein binding Inferred 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

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

331

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform DFF45 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 8656FE45DB003DF3	FASTA	331	36,522
	10 20 30 40 50 60 MEVTGDAGVP ESGEIRTLKP CLLRRNYSRE QHGVAASCLE DLRSKACDIL AIDKSLTPVT 70 80 90 100 110 120 LVLAEDGTIV DDDDYFLCLP SNTKFVALAS NEKWAYNNSD GGTAWISQES FDVDETDSGA 130 140 150 160 170 180 GLKWKNVARQ LKEDLSSIIL LSEEDLQMLV DAPCSDLAQE LRQSCATVQR LQHTLQQVLD 190 200 210 220 230 240 QREEVRQSKQ LLQLYLQALE KEGSLLSKQE ESKAAFGEEV DAVDTGISRE TSSDVALASH 250 260 270 280 290 300 ILTALREKQA PELSLSSQDL ELVTKEDPKA LAVALNWDIK KTETVQEACE RELALRLQQT 310 320 330 QSLHSLRSIS ASKASPPGDL QNPKRARQDP T
	Isoform DFF35. Checksum: EA130F9D27145474	FASTA	268	29,411
	10 20 30 40 50 60 MEVTGDAGVP ESGEIRTLKP CLLRRNYSRE QHGVAASCLE DLRSKACDIL AIDKSLTPVT 70 80 90 100 110 120 LVLAEDGTIV DDDDYFLCLP SNTKFVALAS NEKWAYNNSD GGTAWISQES FDVDETDSGA 130 140 150 160 170 180 GLKWKNVARQ LKEDLSSIIL LSEEDLQMLV DAPCSDLAQE LRQSCATVQR LQHTLQQVLD 190 200 210 220 230 240 QREEVRQSKQ LLQLYLQALE KEGSLLSKQE ESKAAFGEEV DAVDTGISRE TSSDVALASH 250 260 ILTALREKQA PELSLSSQDL EVGGNQGH

References

	« Hide 'large scale' referencesShow '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. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., 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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IBX	NMR	-	B	11-100	[»]
1IYR	NMR	-	A	225-331	[»]
1KOY	NMR	-	A	239-300	[»]

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

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	February 9, 2010
This is version 109 of the entry and version 1 of the sequence. [Complete 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.