DFFA
DNA fragmentation factor subunit alpha
Also known as: DFF-45, DFF1, DFF45, DFFA_HUMAN, ICAD
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O00273
- Gene
- DFFA
- Ensembl
- ENSG00000160049
- Chromosome
- 1
- Canonical length
- 331 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Plasma membrane,Cytosol
OverviewNCBI Gene
Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
331 residues, UniProt reviewed canonical sequence.
>O00273|DFFA
1 MEVTGDAGVP ESGEIRTLKP CLLRRNYSRE QHGVAASCLE DLRSKACDIL AIDKSLTPVT
61 LVLAEDGTIV DDDDYFLCLP SNTKFVALAS NEKWAYNNSD GGTAWISQES FDVDETDSGA
121 GLKWKNVARQ LKEDLSSIIL LSEEDLQMLV DAPCSDLAQE LRQSCATVQR LQHTLQQVLD
181 QREEVRQSKQ LLQLYLQALE KEGSLLSKQE ESKAAFGEEV DAVDTGISRE TSSDVALASH
241 ILTALREKQA PELSLSSQDL ELVTKEDPKA LAVALNWDIK KTETVQEACE RELALRLQQT
301 QSLHSLRSIS ASKASPPGDL QNPKRARQDP TLocalizationUniProt · AlphaFold · HPA
Whether an antibody against DFFA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.42
- Highest tissue expression
- 19 nTPM
Expression across tissuesHPA
Tissue
- placenta: 19 nTPM
- parathyroid gland: 17 nTPM
- esophagus: 16 nTPM
- kidney: 16 nTPM
- midbrain: 16 nTPM
- tonsil: 15 nTPM
Single-cell type
- cytotrophoblasts: 117 nCPM
- late spermatids: 115 nCPM
- migrating cytotrophoblasts: 98 nCPM
- esophageal suprabasal cells: 82 nCPM
- syncytiotrophoblasts: 80 nCPM
- esophageal basal cells: 79 nCPM
Immune cell
- NK-cell: 18 nTPM
- memory B-cell: 17 nTPM
- T-reg: 16 nTPM
- naive B-cell: 16 nTPM
- gdT-cell: 15 nTPM
- memory CD8 T-cell: 14 nTPM
Brain region
- cerebellum: 38 nTPM
- midbrain: 36 nTPM
- thalamus: 34 nTPM
- white matter: 34 nTPM
- pons: 33 nTPM
- basal ganglia: 33 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.16
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.32
- DepMap mean gene effect
- 0.05
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic DNA fragmentation
- apoptotic process
- negative regulation of apoptotic DNA fragmentation
- negative regulation of execution phase of apoptosis
- positive regulation of apoptotic process
- thymocyte apoptotic process
Molecular functions
- protein folding chaperone
- deoxyribonuclease inhibitor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- CIDE-N domain
- CIDE-N domain
- DNA fragmentation factor 45kDa, middle domain
- DNA fragmentation factor 45
- DNA fragmentation factor 45kDa, C-terminal
- DNA Fragmentation factor 45kDa, C terminal domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of DFFA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads DFFA as an antibody target. Whether an autoantibody or antibody against DFFA could matter depends on whether native DFFA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
DFFA is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label DFFA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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