B6VQ60 · BRCA1_CAEEL
- ProteinBreast cancer type 1 susceptibility protein homolog
- Genebrc-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids612 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase that specifically mediates the formation of polyubiquitin chains and plays a central role in DNA repair (PubMed:16628214).
Plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by UV and ionizing radiation for example (PubMed:14711411, PubMed:16628214, PubMed:24424777, PubMed:26903030, PubMed:30383754).
Functions in double-strand break repair, and is required for homologous recombination between sister chromatids in meiotic and mitotic cells (PubMed:18219312, PubMed:19646877, PubMed:24424777, PubMed:26903030).
In particular, protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability (PubMed:14711411, PubMed:18219312, PubMed:24424777).
Required for normal cell cycle progression (PubMed:20207739).
Along with brap-2 modulates the expression of cell cycle arrest protein cki-1 in response to increased levels of reactive oxygen species (PubMed:20207739).
Constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity (PubMed:14711411).
When bound to chromatin, the brc-1-brd-1 heterodimer within the CeBCD complex is inactive during normal conditions, but in response to DNA damage, the brc-1-brd-1 heterodimer associates with other proteins such as the recombinase rad-51 or the E2-ubiquitin-conjugating enzyme let-70, which activate the CeBCD complex as an E3-ubiquitin ligase (PubMed:16628214).
Moreover, association between the brc-1-brd-1 heterodimer and rad-51 and let-70, probably requires DNA checkpoint proteins such as atl-1 and mre-11 in order to induce ubiquitination at DNA damage sites (PubMed:16628214).
To this end, the brc-1-brd-1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:14711411).
Plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by UV and ionizing radiation for example (PubMed:14711411, PubMed:16628214, PubMed:24424777, PubMed:26903030, PubMed:30383754).
Functions in double-strand break repair, and is required for homologous recombination between sister chromatids in meiotic and mitotic cells (PubMed:18219312, PubMed:19646877, PubMed:24424777, PubMed:26903030).
In particular, protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability (PubMed:14711411, PubMed:18219312, PubMed:24424777).
Required for normal cell cycle progression (PubMed:20207739).
Along with brap-2 modulates the expression of cell cycle arrest protein cki-1 in response to increased levels of reactive oxygen species (PubMed:20207739).
Constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity (PubMed:14711411).
When bound to chromatin, the brc-1-brd-1 heterodimer within the CeBCD complex is inactive during normal conditions, but in response to DNA damage, the brc-1-brd-1 heterodimer associates with other proteins such as the recombinase rad-51 or the E2-ubiquitin-conjugating enzyme let-70, which activate the CeBCD complex as an E3-ubiquitin ligase (PubMed:16628214).
Moreover, association between the brc-1-brd-1 heterodimer and rad-51 and let-70, probably requires DNA checkpoint proteins such as atl-1 and mre-11 in order to induce ubiquitination at DNA damage sites (PubMed:16628214).
To this end, the brc-1-brd-1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:14711411).
Catalytic activity
Activity regulation
E3 ubiquitin-protein ligase activity of CeBCD complexes occurs at DNA damage sites. Following DNA damage, E3 ubiquitin-protein ligase activity is reduced by caffeine treatment (inhibitor of ATM and ATK kinase activity).
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | BRCA1-BARD1 complex | |
Cellular Component | chromosome | |
Cellular Component | cytoplasm | |
Molecular Function | metal ion binding | |
Molecular Function | ubiquitin protein ligase activity | |
Biological Process | apoptotic process | |
Biological Process | cellular response to ionizing radiation | |
Biological Process | DNA damage response | |
Biological Process | DNA repair | |
Biological Process | double-strand break repair via homologous recombination | |
Biological Process | embryo development ending in birth or egg hatching | |
Biological Process | meiotic chromosome separation | |
Biological Process | mitotic sister chromatid segregation | |
Biological Process | nucleotide-excision repair | |
Biological Process | positive regulation of double-strand break repair via homologous recombination | |
Biological Process | protein ubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBreast cancer type 1 susceptibility protein homolog
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionB6VQ60
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly localizes to the nucleus and a small proportion is chromatin bound (PubMed:30383754).
Co-localizes with brd-1 in germline nuclei at meiotic prophase I (PubMed:30383754).
At the transition between mid- and late- pachytene, localization together with brd-1 is less diffuse and becomes a linear pattern along the chromosomes (PubMed:30383754).
In late pachytene nuclei, co-localizes with brd-1 and syp-1 at crossover sites and the short arm of the bivalent (PubMed:30383754).
Co-localizes with the pro-crossover factors cosa-1, zhp-3 and msh-5 at crossover sites in mid-late pachytene nuclei (PubMed:30383754).
Co-localizes with plk-2 in pachytene nuclei (PubMed:30383754).
Localizes to DNA damage sites on chromatin following DNA damage
Co-localizes with brd-1 in germline nuclei at meiotic prophase I (PubMed:30383754).
At the transition between mid- and late- pachytene, localization together with brd-1 is less diffuse and becomes a linear pattern along the chromosomes (PubMed:30383754).
In late pachytene nuclei, co-localizes with brd-1 and syp-1 at crossover sites and the short arm of the bivalent (PubMed:30383754).
Co-localizes with the pro-crossover factors cosa-1, zhp-3 and msh-5 at crossover sites in mid-late pachytene nuclei (PubMed:30383754).
Co-localizes with plk-2 in pachytene nuclei (PubMed:30383754).
Localizes to DNA damage sites on chromatin following DNA damage
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Animals are viable (PubMed:18219312, PubMed:19646877).
However, there is defective double strand break repair (PubMed:18219312, PubMed:19646877, PubMed:26903030).
During the early stages of meiosis, this is characterized by impaired homologous recombination in germ cells with increased apoptosis and increased numbers of rad-51-positive foci (PubMed:18219312, PubMed:19646877).
Increased sensitivity to UV and IR irradiation and topoisomerase inhibitor camptothecin compared to wild-type (PubMed:24424777, PubMed:26903030).
Following either IR irradiation or camptothecin treatment, there is reduced egg hatching (PubMed:26903030).
Furthermore, there are also DNA damage repair defects following ionizing radiation and UV irradiation characterized by reduced ubiquitination at DNA damage sites and reduced rad-51-positive foci, respectively (PubMed:16628214, PubMed:24424777, PubMed:26903030).
High levels of embryonic lethality and abolished brd-1 expression following DNA damage induced by ionising radiation (PubMed:30383754).
Double knockout with brd-1 impairs rad-51 localization to DNA damage sites following DNA damage induced by ionising radiation (PubMed:30383754).
RNAi-mediated knockdown results in high X chromosome non-disjunction leading to a high incidence of males (him) phenotype (PubMed:14711411).
RNAi-mediated knockdown in addition to gamma-irradiation at the L4 stage of larval development, results in reduced progeny, increased cep-1/p53-dependent germ cell death, chromosome fragmentation and DNA repair defects (PubMed:14711411).
However, there is defective double strand break repair (PubMed:18219312, PubMed:19646877, PubMed:26903030).
During the early stages of meiosis, this is characterized by impaired homologous recombination in germ cells with increased apoptosis and increased numbers of rad-51-positive foci (PubMed:18219312, PubMed:19646877).
Increased sensitivity to UV and IR irradiation and topoisomerase inhibitor camptothecin compared to wild-type (PubMed:24424777, PubMed:26903030).
Following either IR irradiation or camptothecin treatment, there is reduced egg hatching (PubMed:26903030).
Furthermore, there are also DNA damage repair defects following ionizing radiation and UV irradiation characterized by reduced ubiquitination at DNA damage sites and reduced rad-51-positive foci, respectively (PubMed:16628214, PubMed:24424777, PubMed:26903030).
High levels of embryonic lethality and abolished brd-1 expression following DNA damage induced by ionising radiation (PubMed:30383754).
Double knockout with brd-1 impairs rad-51 localization to DNA damage sites following DNA damage induced by ionising radiation (PubMed:30383754).
RNAi-mediated knockdown results in high X chromosome non-disjunction leading to a high incidence of males (him) phenotype (PubMed:14711411).
RNAi-mediated knockdown in addition to gamma-irradiation at the L4 stage of larval development, results in reduced progeny, increased cep-1/p53-dependent germ cell death, chromosome fragmentation and DNA repair defects (PubMed:14711411).
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000442581 | 1-612 | Breast cancer type 1 susceptibility protein homolog | |||
Sequence: MADVALRITETVARLQKELKCGICCSTYKDPILSTCFHIFCRSCINACFERKRKVQCPICRSVLDKRSCRDTYQITMAVQNYLKLSEAFKKDIENMNTFKSLPPEKMFMESQMPLDITIIPENDGKRCAPDFAIPFLPVRRKRPSRPQPPSAFAEEPAEPVEPPEPATKQPVELQSRVFPLEKLKKDVETSTETYKISREELKNVDIEEYINTLRENSTEIDEIDALFQLMPTMRQFLRNNINQLMEKFHVAPPKKSEKPANRRVSFASSQDLENIKIMTASESLETPPEPIQKLAQKPEVFKSTQNLIDLNLNTAVKKPVVVASDDDEVVEDSEGELQIDEDDLANVTCATSSTTLDADRTPKAIQDDEDRIDDELSQVPKTIVCSRIHNDADEVVGLELLSDFYHKFLSNACRFAEDVNEHTTHLVMMNSEGRSISQKSTAYLYAIARKCVIVGRQWLVDCITTGLLLSEADYTITSCSSTIPVKIPPSIGSEMGWLRSRNDEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEILSCYENLSPEKLYIIFSKHSKAIEESKNIENLYKCDVVTMEWVLDSISEYLILPTQPYKAVDSIGCLQD |
Post-translational modification
Phosphorylation of CeBCD complexes is required for E3 ubiquitin-protein ligase activity.
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Heterodimer (via RING-type zinc finger) with brd-1 to form the core CeBCD complex (PubMed:14711411, PubMed:16628214).
Brc-1-brd-1 heterodimer-containing CeBCD complexes bound to chromatin are activated as an E3-ubiquitin ligase in response to DNA damage (PubMed:16628214).
The heterodimer interacts with the recombinase rad-51 following ionizing irradiation; the interaction is direct (PubMed:16628214).
The heterodimer interacts the E2-ubiquitin-conjugating enzyme let-70 following ionizing irradiation (PubMed:16628214).
The heterodimer interacts with the pro-crossover proteins msh-5 and syp-3 (PubMed:30383754).
Brc-1-brd-1 heterodimer-containing CeBCD complexes bound to chromatin are activated as an E3-ubiquitin ligase in response to DNA damage (PubMed:16628214).
The heterodimer interacts with the recombinase rad-51 following ionizing irradiation; the interaction is direct (PubMed:16628214).
The heterodimer interacts the E2-ubiquitin-conjugating enzyme let-70 following ionizing irradiation (PubMed:16628214).
The heterodimer interacts with the pro-crossover proteins msh-5 and syp-3 (PubMed:30383754).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | B6VQ60 | brd-1 Q21209 | 4 | EBI-3895496, EBI-3895480 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for zinc finger, region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 21-61 | RING-type | ||||
Sequence: CGICCSTYKDPILSTCFHIFCRSCINACFERKRKVQCPICR | ||||||
Region | 140-173 | Disordered | ||||
Sequence: RRKRPSRPQPPSAFAEEPAEPVEPPEPATKQPVE | ||||||
Compositional bias | 142-167 | Pro residues | ||||
Sequence: KRPSRPQPPSAFAEEPAEPVEPPEPA | ||||||
Domain | 415-477 | BRCT 1 | ||||
Sequence: RFAEDVNEHTTHLVMMNSEGRSISQKSTAYLYAIARKCVIVGRQWLVDCITTGLLLSEADYTI | ||||||
Domain | 505-603 | BRCT 2 | ||||
Sequence: EHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEILSCYENLSPEKLYIIFSKHSKAIEESKNIENLYKCDVVTMEWVLDSISEYLILPTQPYKA |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
B6VQ60-1
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.
- Namea
- Length612
- Mass (Da)69,718
- Last updated2008-12-16 v1
- Checksum159B448AEE153B8B
B6VQ60-2
- Nameb
- Differences from canonical
- 1-495: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A679L8N4 | A0A679L8N4_CAEEL | brc-1 | 608 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_059259 | 1-495 | in isoform b | |||
Sequence: Missing | ||||||
Compositional bias | 142-167 | Pro residues | ||||
Sequence: KRPSRPQPPSAFAEEPAEPVEPPEPA |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BX284603 EMBL· GenBank· DDBJ | CAR97812.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BX284603 EMBL· GenBank· DDBJ | CAR97813.1 EMBL· GenBank· DDBJ | Genomic DNA |