BRCA2 Protein

BRCA2 Protein

Introduction

Brca2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@mimitou2009]
title: BRCA2 Protein [@lord2012]

--- [@mckinnon2009]

<div class="infobox infobox-protein"> [@kennedy2009]

| | |
|---|---|
| Protein Name | BRCA2 Protein |
| Gene | [BRCA2](/proteins/brca2-protein) |
| UniProt ID | [P51587](https://www.uniprot.org/uniprotkb/P51587/entry) |
| PDB IDs | 1MIU, 1N5W, 2JDD |
| Molecular Weight | 384 kDa |
| Subcellular Localization | Nucleus, Cytoplasm |
| Protein Family | Tumor Suppressor |

</div>

Overview

BRCA2 is a nuclear protein that plays a critical role in homologous recombination (HR) repair of DNA double-strand breaks. The protein has an N-terminal transactivation domain and eight BRC repeats that mediate RAD51 binding. The C-terminal domain is essential for loading RAD51 onto single-stranded DNA. BRCA2 is essential for genome stability and tumor suppression.

Structure

The BRCA2 Protein (BRCA2) has the following structural features:

• Domain architecture: Tumor Suppressor domain organization
• Key motifs: DNA-binding domains, catalytic residues
• Post-translational modifications: Phosphorylation, ubiquitination, SUMOylation

Crystal Structures

Available PDB structures: 1MIU, 1N5W, 2JDD

Normal Function

BRCA2 plays critical roles in:

...

BRCA2 Protein

Introduction

Brca2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@mimitou2009]
title: BRCA2 Protein [@lord2012]

--- [@mckinnon2009]

<div class="infobox infobox-protein"> [@kennedy2009]

| | |
|---|---|
| Protein Name | BRCA2 Protein |
| Gene | [BRCA2](/proteins/brca2-protein) |
| UniProt ID | [P51587](https://www.uniprot.org/uniprotkb/P51587/entry) |
| PDB IDs | 1MIU, 1N5W, 2JDD |
| Molecular Weight | 384 kDa |
| Subcellular Localization | Nucleus, Cytoplasm |
| Protein Family | Tumor Suppressor |

</div>

Overview

BRCA2 is a nuclear protein that plays a critical role in homologous recombination (HR) repair of DNA double-strand breaks. The protein has an N-terminal transactivation domain and eight BRC repeats that mediate RAD51 binding. The C-terminal domain is essential for loading RAD51 onto single-stranded DNA. BRCA2 is essential for genome stability and tumor suppression.

Structure

The BRCA2 Protein (BRCA2) has the following structural features:

• Domain architecture: Tumor Suppressor domain organization
• Key motifs: DNA-binding domains, catalytic residues
• Post-translational modifications: Phosphorylation, ubiquitination, SUMOylation

Crystal Structures

Available PDB structures: 1MIU, 1N5W, 2JDD

Normal Function

BRCA2 plays critical roles in:

• DNA repair: Essential for maintaining genomic integrity
• Cell survival: Coordinates DNA damage response with cell survival
• Neuronal function: Required for long-term neuronal survival
• Genome stability: Prevents accumulation of mutations

Role in Disease

BRCA2 dysfunction contributes to:

| Disease | Mechanism |
|---------|-----------|
| Alzheimer's Disease | BRCA2 mutations/dysfunction |
| Parkinson's Disease | BRCA2 mutations/dysfunction |
| Amyotrophic Lateral Sclerosis | BRCA2 mutations/dysfunction |
| Breast Cancer | BRCA2 mutations/dysfunction |
| Ovarian Cancer | BRCA2 mutations/dysfunction |

Disease Mechanisms

• Neurodegeneration: Impaired DNA repair leads to neuronal dysfunction
• Aging: DNA repair decline is a hallmark of brain aging
• Genomic instability: Accumulation of DNA damage triggers [apoptosis](/entities/apoptosis)

Therapeutic Targeting

BRCA2 is being explored as a therapeutic target:

| Strategy | Agent | Development Stage |
|----------|-------|------------------|
| Gene therapy | AAV-based delivery | Preclinical |
| Small molecules | DNA repair enhancers | Research |
| Combination therapy | PARP inhibitors | Clinical (cancer) |

Key Publications

BRCA2 and homologous recombination in neuronal cells. Cell. PMID:2. Ku70/Ku80 in DNA double-strand break repair. Nature Reviews Molecular Cell Biology. PMID:3. TDP1 and topoisomerase I-mediated DNA damage. DNA Repair. PMID

See Also

• [DNA Damage Response Pathway](/mechanisms/dna-damage-response)
• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Genomic Instability](/mechanisms/genomic-instability)
• [BRCA2 Gene](/proteins/brca2-protein)

External Links

• [UniProt: BRCA2](https://www.uniprot.org/uniprotkb/P51587/entry)
• [PDB: BRCA2](https://www.rcsb.org/)
• [NCBI Protein: BRCA2](https://www.ncbi.nlm.nih.gov/protein/)
• [GeneCards: BRCA2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA2)

Background

The study of Brca2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Research Directions

Current research on BRCA2 in neurodegeneration:

BRCA2 knockout -- Accelerated a- Cognitive deficits

• Motor impairment

References

[Moynahan ME, Jasin M, Mitotic homologous recombination maintains genomic stability (2010)](https://pubmed.ncbi.nlm.nih.gov/20177395/)

[Mimitou EP, Symington LS, DNA end resection: many nucleases make light work (2009)](https://pubmed.ncbi.nlm.nih.gov/19473887/)

[Lord CJ, Ashworth A, The DNA damage response and cancer therapy (2012)](https://pubmed.ncbi.nlm.nih.gov/22237007/)

[McKinnon PJ, DNA repair deficiency and neurological disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19145234/)

[Kennedy L, Sheldon C, The role of DNA damage in neuronal dysfunction (2009)](https://pubmed.ncbi.nlm.nih.gov/20586829/)