Reviewed, UniProtKB/Swiss-Prot O76075 (DFFB_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA fragmentation factor subunit beta
    EC=3.-.-.-
Alternative name(s):
    DNA fragmentation factor 40 kDa subunit
      Short name=DFF-40
    Caspase-activated deoxyribonuclease
      Short name=Caspase-activated DNase
      Short name=CAD
      Short name=Caspase-activated nuclease
      Short name=CPAN

Gene names

Name:	DFFB
Synonyms:	CAD, DFF2, DFF40

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	338 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis. Degrades naked DNA and induces apoptotic morphology.
Enzyme regulation	Inhibited by DFFA (DFF45).
Subunit structure	Heterodimer of DFFA and DFFB.
Subcellular location	Cytoplasm. Nucleus.
Sequence similarities	Contains 1 CIDE-N domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Nuclease
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA fragmentation involved in apoptosis Inferred from direct assay. Source: MGI apoptotic chromosome condensation Inferred from direct assay. Source: UniProtKB intracellular signaling cascade Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: ProtInc nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	caspase-activated deoxyribonuclease activity Ref.1 Traceable author statement. Source: ProtInc enzyme binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DFFA	O00273	1	EBI-1053821,EBI-727171

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: O76075-1)

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 Beta (identifier: O76075-2)

The sequence of this isoform differs from the canonical sequence as follows:
     262-338: IEKKRTIIPT...KRKQPVRKRQ → DGVLLCGPG

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform Gamma (identifier: O76075-3)

The sequence of this isoform differs from the canonical sequence as follows:
     81-116: YVSDIRRFLSAFHEPQVGLIQAAQQLLCDEQAPQRQ → SVGVRARTKTRDTSSLSPGDCQALGNGGRCGQRLFL
     117-338: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform Delta (identifier: O76075-4)

The sequence of this isoform differs from the canonical sequence as follows:
     81-103: YVSDIRRFLSAFHEPQVGLIQAA → WFCHVSQDSLTLLGSSCPPALVS
     104-338: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 338

338

DNA fragmentation factor subunit beta

PRO_0000144713

Regions

Domain

4 – 80

77

CIDE-N

Natural variations

Alternative sequence

81 – 116

36

YVSDI…APQRQ → SVGVRARTKTRDTSSLSPGD CQALGNGGRCGQRLFL in isoform Gamma.

VSP_001081

Alternative sequence

81 – 103

23

YVSDI…LIQAA → WFCHVSQDSLTLLGSSCPPA LVS in isoform Delta.

VSP_001083

Alternative sequence

104 – 338

235

Missing in isoform Delta.

VSP_001084

Alternative sequence

117 – 338

222

Missing in isoform Gamma.

VSP_001082

Alternative sequence

262 – 338

77

IEKKR…VRKRQ → DGVLLCGPG in isoform Beta.

VSP_001080

Natural variant

196

1

R → K: dbSNP rs12738235. Ref.7

VAR_009305

Natural variant

277

1

K → R: dbSNP rs12564400.

VAR_048737

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

338

Helix Strand Turn

Details...

Beta strand

9 – 11

3

Beta strand

13 – 16

4

Helix

26 – 36

11

Turn

41 – 43

3

Beta strand

44 – 51

8

Beta strand

57 – 59

3

Beta strand

69 – 72

4

Beta strand

74 – 76

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 0B0F3F8D91209389	FASTA	338	39,110
	10 20 30 40 50 60 MLQKPKSVKL RALRSPRKFG VAGRSCQEVL RKGCLRFQLP ERGSRLCLYE DGTELTEDYF 70 80 90 100 110 120 PSVPDNAELV LLTLGQAWQG YVSDIRRFLS AFHEPQVGLI QAAQQLLCDE QAPQRQRLLA 130 140 150 160 170 180 DLLHNVSQNI AAETRAEDPP WFEGLESRFQ SKSGYLRYSC ESRIRSYLRE VSSYPSTVGA 190 200 210 220 230 240 EAQEEFLRVL GSMCQRLRSM QYNGSYFDRG AKGGSRLCTP EGWFSCQGPF DMDSCLSRHS 250 260 270 280 290 300 INPYSNRESR ILFSTWNLDH IIEKKRTIIP TLVEAIKEQD GREVDWEYFY GLLFTSENLK 310 320 330 LVHIVCHKKT THKLNCDPSR IYKPQTRLKR KQPVRKRQ
	Isoform Beta. Checksum: 26AC88793BE46E7E	FASTA	270	30,649
	10 20 30 40 50 60 MLQKPKSVKL RALRSPRKFG VAGRSCQEVL RKGCLRFQLP ERGSRLCLYE DGTELTEDYF 70 80 90 100 110 120 PSVPDNAELV LLTLGQAWQG YVSDIRRFLS AFHEPQVGLI QAAQQLLCDE QAPQRQRLLA 130 140 150 160 170 180 DLLHNVSQNI AAETRAEDPP WFEGLESRFQ SKSGYLRYSC ESRIRSYLRE VSSYPSTVGA 190 200 210 220 230 240 EAQEEFLRVL GSMCQRLRSM QYNGSYFDRG AKGGSRLCTP EGWFSCQGPF DMDSCLSRHS 250 260 270 INPYSNRESR ILFSTWNLDH IDGVLLCGPG
	Isoform Gamma. Checksum: F6C9A328ACBB54EE	FASTA	116	12,800
	10 20 30 40 50 60 MLQKPKSVKL RALRSPRKFG VAGRSCQEVL RKGCLRFQLP ERGSRLCLYE DGTELTEDYF 70 80 90 100 110 PSVPDNAELV LLTLGQAWQG SVGVRARTKT RDTSSLSPGD CQALGNGGRC GQRLFL
	Isoform Delta. Checksum: F9BDC40AC25E4500	FASTA	103	11,482
	10 20 30 40 50 60 MLQKPKSVKL RALRSPRKFG VAGRSCQEVL RKGCLRFQLP ERGSRLCLYE DGTELTEDYF 70 80 90 100 PSVPDNAELV LLTLGQAWQG WFCHVSQDSL TLLGSSCPPA LVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis." Liu X., Li P., Widlak P., Zou H., Luo X., Garrard W.T., Wang X. Proc. Natl. Acad. Sci. U.S.A. 95:8461-8466(1998) [PubMed: 9671700] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[2]	"Molecular cloning and characterization of human caspase-activated DNase." Mukae N., Enari M., Sakahira H., Fukuda Y., Inazawa J., Toh H., Nagata S. Proc. Natl. Acad. Sci. U.S.A. 95:9123-9128(1998) [PubMed: 9689044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[3]	"CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45." Halenbeck R., MacDonald H., Roulston A., Chen T.T., Conroy L., Williams L.T. Curr. Biol. 8:537-540(1998) [PubMed: 9560346] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). Tissue: Pancreas.
[4]	"DFF40 delta." Nakagawara A., Takahashi M., Takada N., Kawamoto T. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA; GAMMA AND DELTA). Tissue: Fetal brain.
[5]	"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 ALPHA). Tissue: Lung.
[6]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[7]	"Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene." Judson H., van Roy N., Strain L., Vandesompele J., Van Gele M., Speleman F., Bonthron D.T. Hum. Genet. 106:406-413(2000) [PubMed: 10830907] [Abstract] Cited for: VARIANT LYS-196.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF064019 mRNA. Translation: AAC39920.1.
AB013918 mRNA. Translation: BAA32250.1.
AF039210 mRNA. Translation: AAC39709.1.
AB028911 mRNA. Translation: BAB40447.1.
AB028912 mRNA. Translation: BAB40448.1.
AB028913 mRNA. Translation: BAB40449.1.
BC048797 mRNA. Translation: AAH48797.1.

IPI

IPI00008794.
IPI00179341.
IPI00218518.
IPI00883793.

RefSeq

NP_004393.1.

UniGene

Hs.133089

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IBX	NMR	-	A	1-80	[»]

SMR

O76075. Positions 82-326.

ModBase

Search...

Protein-protein interaction databases

IntAct

O76075. 1 interaction.

Proteomic databases

PRIDE

O76075.

Genome annotation databases

Ensembl

ENSG00000169598. Homo sapiens. [Contig view]

GeneID

1677.

KEGG

hsa:1677.

Organism-specific databases

GeneCards

GC01P003797.

HGNC

HGNC:2773. DFFB.

HPA

CAB004328.

MIM

601883. gene.

PharmGKB

PA27255.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O76075.

HOVERGEN

O76075.

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

O76075.

Bgee

O76075.

CleanEx

HS_CAD.
HS_DFFB.

GermOnline

ENSG00000169598. Homo sapiens.

Family and domain databases

InterPro

IPR015311. Apoptosis_DFF40.
IPR003508. CAD.
[Graphical view]

Pfam

PF02017. CIDE-N. 1 hit.
PF09230. DFF40. 1 hit.
[Graphical view]

PROSITE

PS51135. CIDE_N. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6902.

SOURCE

Search...

Entry information

Entry name

DFFB_HUMAN

Accession

Primary (citable) accession number: O76075
Secondary accession number(s): O60521 , Q9BYI4, Q9BYI5, Q9BYI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)