B6VQ60 · BRCA1_CAEEL

  • Protein
    Breast cancer type 1 susceptibility protein homolog
  • Gene
    brc-1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

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

AspectTerm
Cellular ComponentBRCA1-BARD1 complex
Cellular Componentchromosome
Cellular Componentcytoplasm
Molecular Functionmetal ion binding
Molecular Functionubiquitin protein ligase activity
Biological Processapoptotic process
Biological Processcellular response to ionizing radiation
Biological ProcessDNA damage response
Biological ProcessDNA repair
Biological Processdouble-strand break repair via homologous recombination
Biological Processembryo development ending in birth or egg hatching
Biological Processmeiotic chromosome separation
Biological Processmitotic sister chromatid segregation
Biological Processnucleotide-excision repair
Biological Processpositive regulation of double-strand break repair via homologous recombination
Biological Processprotein ubiquitination

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Breast cancer type 1 susceptibility protein homolog
  • EC number
  • Alternative names
    • RING-type E3 ubiquitin transferase BRCA1

Gene names

    • Name
      brc-1
    • ORF names
      C36A4.8

Organism names

  • Taxonomic identifier
  • Organism
  • Strain
    • Bristol N2
  • Taxonomic lineage
    Eukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis

Accessions

  • Primary accession
    B6VQ60
  • Secondary accessions
    • B6VQ61

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Chromosome
Cytoplasm
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

Keywords

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).

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004425811-612Breast cancer type 1 susceptibility protein homolog

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).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY B6VQ60brd-1 Q212094EBI-3895496, EBI-3895480
View interactors in UniProtKB
View CPX-375 in Complex Portal

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for zinc finger, region, compositional bias, domain.

TypeIDPosition(s)Description
Zinc finger21-61RING-type
Region140-173Disordered
Compositional bias142-167Pro residues
Domain415-477BRCT 1
Domain505-603BRCT 2

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    612
  • Mass (Da)
    69,718
  • Last updated
    2008-12-16 v1
  • Checksum
    159B448AEE153B8B
MADVALRITETVARLQKELKCGICCSTYKDPILSTCFHIFCRSCINACFERKRKVQCPICRSVLDKRSCRDTYQITMAVQNYLKLSEAFKKDIENMNTFKSLPPEKMFMESQMPLDITIIPENDGKRCAPDFAIPFLPVRRKRPSRPQPPSAFAEEPAEPVEPPEPATKQPVELQSRVFPLEKLKKDVETSTETYKISREELKNVDIEEYINTLRENSTEIDEIDALFQLMPTMRQFLRNNINQLMEKFHVAPPKKSEKPANRRVSFASSQDLENIKIMTASESLETPPEPIQKLAQKPEVFKSTQNLIDLNLNTAVKKPVVVASDDDEVVEDSEGELQIDEDDLANVTCATSSTTLDADRTPKAIQDDEDRIDDELSQVPKTIVCSRIHNDADEVVGLELLSDFYHKFLSNACRFAEDVNEHTTHLVMMNSEGRSISQKSTAYLYAIARKCVIVGRQWLVDCITTGLLLSEADYTITSCSSTIPVKIPPSIGSEMGWLRSRNDEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEILSCYENLSPEKLYIIFSKHSKAIEESKNIENLYKCDVVTMEWVLDSISEYLILPTQPYKAVDSIGCLQD

B6VQ60-2

  • Name
    b
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A679L8N4A0A679L8N4_CAEELbrc-1608

Features

Showing features for alternative sequence, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0592591-495in isoform b
Compositional bias142-167Pro residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
BX284603
EMBL· GenBank· DDBJ
CAR97812.1
EMBL· GenBank· DDBJ
Genomic DNA
BX284603
EMBL· GenBank· DDBJ
CAR97813.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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