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Protein / target

Breast cancer type 1 susceptibility protein

Encoded byBRCA1P38398Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
Druggable Family
15
Research papers

Protein at a glance

Biological role

Transcription cis-regulatory region binding

Strongest disease association

Breast Neoplasms

Via encoding gene BRCA1 · Genetic evidence · score 0.98

Research activity

Emerging research

15 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.

View complete UniProt function annotation

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719)

Subcellular location

NucleusChromosomeCytoplasm
Domains and Gene Ontology detail (73)

Domains & features

BRCT 1BRCT 2

Gene Ontology

  • CBRCA1-A complex
  • CBRCA1-BARD1 complex
  • Cchromosome
  • Ccytoplasm
  • Cgamma-tubulin ring complex
  • Clateral element
  • Cnuclear body
  • Cnucleoplasm
  • Cnucleus
  • Cplasma membrane
  • Cprotein-containing complex
  • Cribonucleoprotein complex

1863 aa · 208 kDa · 8 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationUniProt · GOLipid & lipoprotein metabolismGOTranscriptional regulationUniProt · GO
View supporting evidence

Cell-cycle regulation

  • ·E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked p…
  • ·mitotic G2/M transition checkpoint

Lipid & lipoprotein metabolism

  • ·fatty acid biosynthetic process
  • ·negative regulation of fatty acid biosynthetic process

Transcriptional regulation

  • ·E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked p…
  • ·transcription cis-regulatory region binding
  • ·transcription coactivator activity
  • ·DNA-templated transcription

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene BRCA1

Gene-level evidence surfaced through the gene BRCA1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Breast Neoplasms
0.99Well supported

Genetic evidence dominant · Open Targets 0.84

Neoplasms
0.98Well supported

Genetic evidence dominant · Open Targets 0.78

Ovarian Neoplasms
0.97Well supported

Genetic evidence dominant · Open Targets 0.81

View evidence synthesis (3)
Breast NeoplasmsWell supported
0.99
agreement 0.881.00
Genetic60%Somatic mutation31%Literature9%Genetic literaturedup

Open Targets aggregate 0.84 · 3 independent evidence families · 1 not counted as duplicate

NeoplasmsWell supported
0.98
agreement 0.861.00
Genetic67%Pathway23%Literature10%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

Ovarian NeoplasmsWell supported
0.97
agreement 0.851.00
Genetic56%Somatic mutation35%Literature9%Genetic literaturedup

Open Targets aggregate 0.81 · 3 independent evidence families · 1 not counted as duplicate

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Breast Neoplasms0.84
Ovarian Neoplasms0.81
Neoplasms0.78

Tractability

Small moleculesEmerging

Feasibility evidence (druggable family) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Druggable FamilyAB · GO CC high confPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

15 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Colaprico A · Nucleic acids research · 2016

Kaufman B · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015

Abida W · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020

Won KA · International journal of oncology · 2020

Geyer CE Jr · Annals of oncology : official journal of the European Society for Medical Oncology · 2022

Recent

Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a <i>BRCA1</i> or <i>BRCA2</i> Gene Alteration.

Abida W · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020

Europe PMC papers linked directly to this protein.