UniProtKB - B6VQ60 (BRCA1_CAEEL)
Breast cancer type 1 susceptibility protein homolog
brc-1
Functioni
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).
8 PublicationsCatalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication EC:2.3.2.27
Activity regulationi
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 PublicationView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 21 – 61 | RING-typePROSITE-ProRule annotationAdd BLAST | 41 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- ubiquitin protein ligase activity Source: WormBase
- ubiquitin-protein transferase activity Source: GO_Central
GO - Biological processi
- apoptotic process Source: WormBase
- cellular response to DNA damage stimulus Source: WormBase
- cellular response to ionizing radiation Source: UniProtKB
- DNA repair Source: WormBase
- double-strand break repair via homologous recombination Source: WormBase
- embryo development ending in birth or egg hatching Source: UniProtKB
- meiotic chromosome separation Source: WormBase
- mitotic sister chromatid segregation Source: UniProtKB
- negative regulation of fatty acid biosynthetic process Source: GO_Central
- negative regulation of histone acetylation Source: GO_Central
- nucleotide-excision repair Source: WormBase
- positive regulation of double-strand break repair via homologous recombination Source: ComplexPortal
- positive regulation of histone acetylation Source: GO_Central
- positive regulation of response to DNA damage stimulus Source: ComplexPortal
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- protein ubiquitination Source: WormBase
Keywordsi
Molecular function | Transferase |
Biological process | Cell cycle, DNA damage, DNA repair |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Breast cancer type 1 susceptibility protein homologBy similarity (EC:2.3.2.271 Publication)Alternative name(s): RING-type E3 ubiquitin transferase BRCA1By similarity |
Gene namesi | ORF Names:C36A4.8Imported |
Organismi | Caenorhabditis elegansImported |
Taxonomic identifieri | 6239 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditina › Rhabditomorpha › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis |
Proteomesi |
|
Organism-specific databases
WormBasei | C36A4.8a ; CE43190 ; WBGene00000264 ; brc-1 C36A4.8b ; CE43228 ; WBGene00000264 ; brc-1 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Chromosome 2 Publications
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.2 Publications
Nucleus
- BRCA1-A complex Source: GO_Central
- BRCA1-BARD1 complex Source: WormBase
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- chromosome Source: UniProtKB-SubCell
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Chromosome, Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000442581 | 1 – 612 | Breast cancer type 1 susceptibility protein homologCuratedAdd BLAST | 612 |
Post-translational modificationi
Proteomic databases
EPDi | B6VQ60 |
PaxDbi | B6VQ60 |
PeptideAtlasi | B6VQ60 |
Expressioni
Gene expression databases
Bgeei | WBGene00000264, Expressed in adult organism and 5 other tissues |
Interactioni
Subunit structurei
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).
3 PublicationsBinary interactionsi
B6VQ60
With | #Exp. | IntAct |
---|---|---|
brd-1 [Q21209] | 4 | EBI-3895496,EBI-3895480 |
Protein-protein interaction databases
ComplexPortali | CPX-375, brc-1/brd-1 complex |
IntActi | B6VQ60, 1 interactor |
STRINGi | 6239.C36A4.8a |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 415 – 477 | BRCT 1PROSITE-ProRule annotationAdd BLAST | 63 | |
Domaini | 505 – 603 | BRCT 2PROSITE-ProRule annotationAdd BLAST | 99 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 140 – 173 | DisorderedSequence analysisAdd BLAST | 34 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 142 – 167 | Pro residuesSequence analysisAdd BLAST | 26 |
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 21 – 61 | RING-typePROSITE-ProRule annotationAdd BLAST | 41 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG4362, Eukaryota |
GeneTreei | ENSGT00440000034289 |
HOGENOMi | CLU_446355_0_0_1 |
InParanoidi | B6VQ60 |
OMAi | SHVWELP |
OrthoDBi | 472443at2759 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit 3.40.50.10190, 2 hits |
InterProi | View protein in InterPro IPR031099, BRCA1-associated IPR001357, BRCT_dom IPR036420, BRCT_dom_sf IPR018957, Znf_C3HC4_RING-type IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR13763, PTHR13763, 2 hits |
Pfami | View protein in Pfam PF16589, BRCT_2, 1 hit PF00097, zf-C3HC4, 1 hit |
SMARTi | View protein in SMART SM00292, BRCT, 2 hits SM00184, RING, 1 hit |
SUPFAMi | SSF52113, SSF52113, 2 hits |
PROSITEi | View protein in PROSITE PS50172, BRCT, 2 hits PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MADVALRITE TVARLQKELK CGICCSTYKD PILSTCFHIF CRSCINACFE
60 70 80 90 100
RKRKVQCPIC RSVLDKRSCR DTYQITMAVQ NYLKLSEAFK KDIENMNTFK
110 120 130 140 150
SLPPEKMFME SQMPLDITII PENDGKRCAP DFAIPFLPVR RKRPSRPQPP
160 170 180 190 200
SAFAEEPAEP VEPPEPATKQ PVELQSRVFP LEKLKKDVET STETYKISRE
210 220 230 240 250
ELKNVDIEEY INTLRENSTE IDEIDALFQL MPTMRQFLRN NINQLMEKFH
260 270 280 290 300
VAPPKKSEKP ANRRVSFASS QDLENIKIMT ASESLETPPE PIQKLAQKPE
310 320 330 340 350
VFKSTQNLID LNLNTAVKKP VVVASDDDEV VEDSEGELQI DEDDLANVTC
360 370 380 390 400
ATSSTTLDAD RTPKAIQDDE DRIDDELSQV PKTIVCSRIH NDADEVVGLE
410 420 430 440 450
LLSDFYHKFL SNACRFAEDV NEHTTHLVMM NSEGRSISQK STAYLYAIAR
460 470 480 490 500
KCVIVGRQWL VDCITTGLLL SEADYTITSC SSTIPVKIPP SIGSEMGWLR
510 520 530 540 550
SRNDEHGKLF AGRRFMILRK FTMNPYFDYK QLIELVQQCG GEILSCYENL
560 570 580 590 600
SPEKLYIIFS KHSKAIEESK NIENLYKCDV VTMEWVLDSI SEYLILPTQP
610
YKAVDSIGCL QD
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A679L8N4 | A0A679L8N4_CAEEL | RING-type E3 ubiquitin transferase ... | brc-1 C36A4.8, CELE_C36A4.8 | 608 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_059259 | 1 – 495 | Missing in isoform b. CuratedAdd BLAST | 495 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BX284603 Genomic DNA Translation: CAR97812.1 BX284603 Genomic DNA Translation: CAR97813.1 |
RefSeqi | NP_001254881.1, NM_001267952.1 NP_001254882.1, NM_001267953.1 [B6VQ60-2] |
Genome annotation databases
EnsemblMetazoai | C36A4.8a.1; C36A4.8a.1; WBGene00000264 [B6VQ60-1] C36A4.8b.1; C36A4.8b.1; WBGene00000264 [B6VQ60-2] |
GeneIDi | 175499 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BX284603 Genomic DNA Translation: CAR97812.1 BX284603 Genomic DNA Translation: CAR97813.1 |
RefSeqi | NP_001254881.1, NM_001267952.1 NP_001254882.1, NM_001267953.1 [B6VQ60-2] |
3D structure databases
AlphaFoldDBi | B6VQ60 |
SMRi | B6VQ60 |
ModBasei | Search... |
Protein-protein interaction databases
ComplexPortali | CPX-375, brc-1/brd-1 complex |
IntActi | B6VQ60, 1 interactor |
STRINGi | 6239.C36A4.8a |
Proteomic databases
EPDi | B6VQ60 |
PaxDbi | B6VQ60 |
PeptideAtlasi | B6VQ60 |
Genome annotation databases
EnsemblMetazoai | C36A4.8a.1; C36A4.8a.1; WBGene00000264 [B6VQ60-1] C36A4.8b.1; C36A4.8b.1; WBGene00000264 [B6VQ60-2] |
GeneIDi | 175499 |
Organism-specific databases
CTDi | 175499 |
WormBasei | C36A4.8a ; CE43190 ; WBGene00000264 ; brc-1 C36A4.8b ; CE43228 ; WBGene00000264 ; brc-1 |
Phylogenomic databases
eggNOGi | KOG4362, Eukaryota |
GeneTreei | ENSGT00440000034289 |
HOGENOMi | CLU_446355_0_0_1 |
InParanoidi | B6VQ60 |
OMAi | SHVWELP |
OrthoDBi | 472443at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Miscellaneous databases
PROi | PR:B6VQ60 |
Gene expression databases
Bgeei | WBGene00000264, Expressed in adult organism and 5 other tissues |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit 3.40.50.10190, 2 hits |
InterProi | View protein in InterPro IPR031099, BRCA1-associated IPR001357, BRCT_dom IPR036420, BRCT_dom_sf IPR018957, Znf_C3HC4_RING-type IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR13763, PTHR13763, 2 hits |
Pfami | View protein in Pfam PF16589, BRCT_2, 1 hit PF00097, zf-C3HC4, 1 hit |
SMARTi | View protein in SMART SM00292, BRCT, 2 hits SM00184, RING, 1 hit |
SUPFAMi | SSF52113, SSF52113, 2 hits |
PROSITEi | View protein in PROSITE PS50172, BRCT, 2 hits PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BRCA1_CAEEL | |
Accessioni | B6VQ60Primary (citable) accession number: B6VQ60 Secondary accession number(s): B6VQ61 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2017 |
Last sequence update: | December 16, 2008 | |
Last modified: | May 25, 2022 | |
This is version 106 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Caenorhabditis annotation project |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Caenorhabditis elegans
Caenorhabditis elegans: entries, gene names and cross-references to WormBase - PATHWAY comments
Index of metabolic and biosynthesis pathways