O00273 (DFFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.
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 Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic DNA fragmentation Inferred from direct assay PubMed 15572351. Source: MGI induction of apoptosis Inferred from electronic annotation. Source: Compara intracellular signal transduction Traceable author statement Ref.1. Source: ProtInc negative regulation of apoptotic process Inferred from direct assay PubMed 9564035. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome nuclear chromatin Inferred from direct assay PubMed 19882353. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	deoxyribonuclease activity Traceable author statement Ref.1. Source: ProtInc
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.9

Modified residue

315

1

Phosphoserine 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.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

331

Helix Strand Turn

Details...

Helix

39 – 50

12

Beta strand

60 – 63

4

Turn

64 – 66

3

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45). Tissue: Mammary gland.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DFF45). Tissue: Eye, Kidney and Skeletal muscle.
[9]	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.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[12]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: 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] [Europe PMC] [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.
AK313317 mRNA. Translation: BAG36122.1.
AL354956 Genomic DNA. Translation: CAI19196.1.
AL354956 Genomic DNA. Translation: CAI19197.1.
CH471130 Genomic DNA. Translation: EAW71656.1.
CH471130 Genomic DNA. Translation: EAW71657.1.
BC000037 mRNA. Translation: AAH00037.1.
BC007112 mRNA. Translation: AAH07112.1.
BC007721 mRNA. Translation: AAH07721.1.

IPI

IPI00010882.
IPI00604566.

RefSeq

NP_004392.1. NM_004401.2.
NP_998731.1. NM_213566.1.

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.

ProteinModelPortal

O00273.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00273. 6 interactions.

MINT

MINT-365527.

STRING

9606.ENSP00000366237.

PTM databases

PhosphoSite

O00273.

Proteomic databases

PaxDb

O00273.

PeptideAtlas

O00273.

PRIDE

O00273.

Protocols and materials databases

DNASU

1676.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377036; ENSP00000366235; ENSG00000160049.
ENST00000377038; ENSP00000366237; ENSG00000160049.

GeneID

1676.

KEGG

hsa:1676.

UCSC

uc001arj.3. human.
uc001ark.3. human.

Organism-specific databases

CTD

1676.

GeneCards

GC01M010516.

HGNC

HGNC:2772. DFFA.

HPA

CAB002679.
HPA018859.
HPA019938.
HPA025230.

MIM

601882. gene.

neXtProt

NX_O00273.

PharmGKB

PA27254.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40170.

HOGENOM

HOG000112204.

HOVERGEN

HBG000683.

InParanoid

O00273.

KO

K02310.

OMA

PCLLRRN.

OrthoDB

EOG4RBQK1.

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

Gene3D

1.10.1490.10. 1 hit.

InterPro

IPR003508. CAD.
IPR027296. DFF-C_dom.
IPR017299. DNA_fragmentation_factor_asu.
IPR015121. DNA_fragmentation_mid_dom.
[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

ChiTaRS

DFFA. human.

EvolutionaryTrace

O00273.

GenomeRNAi

1676.

NextBio

6896.

PMAP-CutDB

Q5T6G5.

SOURCE

Search...

Entry information

Entry name

DFFA_HUMAN

Accession

Primary (citable) accession number: O00273
Secondary accession number(s): Q5T6G5 , Q5T6G6, Q96I97, Q9Y6C6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.