InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BRCA2

Summary

InnateDB Protein

IDBP-22705.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BRCA2

Protein Name

breast cancer 2, early onset

Synonyms

BRCC2; BROVCA2; FACD; FAD; FAD1; FANCD; FANCD1; GLM3; PNCA2;

Species

Homo sapiens

Ensembl Protein

ENSP00000369497

InnateDB Gene

IDBG-22703 (BRCA2)

Protein Structure

UniProt Annotation

Function

Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. {ECO:0000269PubMed:15115758, ECO:0000269PubMed:15199141, ECO:0000269PubMed:15671039, ECO:0000269PubMed:18317453, ECO:0000269PubMed:20729832, ECO:0000269PubMed:20729858, ECO:0000269PubMed:20729859, ECO:0000269PubMed:21084279, ECO:0000269PubMed:24485656}.

Subcellular Localization

Nucleus {ECO:0000305PubMed:21276791}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269PubMed:21276791}.

Disease Associations

Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269PubMed:10399947, ECO:0000269PubMed:10978364, ECO:0000269PubMed:11139248, ECO:0000269PubMed:11241844, ECO:0000269PubMed:11948477, ECO:0000269PubMed:12145750, ECO:0000269PubMed:12373604, ECO:0000269PubMed:12442274, ECO:0000269PubMed:12442275, ECO:0000269PubMed:12938098, ECO:0000269PubMed:14722926, ECO:0000269PubMed:15026808, ECO:0000269PubMed:15172753, ECO:0000269PubMed:15365993, ECO:0000269PubMed:8640237, ECO:0000269PubMed:9150152, ECO:0000269PubMed:9609997, ECO:0000269PubMed:9654203, ECO:0000269PubMed:9971877}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Pancreatic cancer 2 (PNCA2) [MIM:613347]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269PubMed:9140390}. Note=The disease is caused by mutations affecting the gene represented in this entry.Breast-ovarian cancer, familial, 2 (BROVCA2) [MIM:612555]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Fanconi anemia complementation group D1 (FANCD1) [MIM:605724]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269PubMed:12065746, ECO:0000269PubMed:14670928, ECO:0000269PubMed:16825431}. Note=The disease is caused by mutations affecting the gene represented in this entry.Glioma 3 (GLM3) [MIM:613029]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269PubMed:15689453}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Highest levels of expression in breast and thymus, with slightly lower levels in lung, ovary and spleen.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 118 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	119 [view]
Protein-Protein	113 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	5 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0003697	single-stranded DNA binding
GO:0005515	protein binding
GO:0010484	H3 histone acetyltransferase activity
GO:0010485	H4 histone acetyltransferase activity
GO:0043015	gamma-tubulin binding

Biological Process

GO:0000724	double-strand break repair via homologous recombination
GO:0000910	cytokinesis
GO:0001556	oocyte maturation
GO:0001833	inner cell mass cell proliferation
GO:0006281	DNA repair
GO:0006289	nucleotide-excision repair
GO:0006302	double-strand break repair
GO:0006974	cellular response to DNA damage stimulus
GO:0006978	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007141	male meiosis I
GO:0007283	spermatogenesis
GO:0007420	brain development
GO:0007569	cell aging
GO:0008283	cell proliferation
GO:0008585	female gonad development
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010165	response to X-ray
GO:0010225	response to UV-C
GO:0010332	response to gamma radiation
GO:0030097	hemopoiesis
GO:0032465	regulation of cytokinesis
GO:0033600	negative regulation of mammary gland epithelial cell proliferation
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043009	chordate embryonic development
GO:0043966	histone H3 acetylation
GO:0043967	histone H4 acetylation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045931	positive regulation of mitotic cell cycle
GO:0048478	replication fork protection
GO:0051276	chromosome organization
GO:0051298	centrosome duplication

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0030141	secretory granule
GO:0033593	BRCA2-MAGE-D1 complex
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR002093 BRCA2 repeat
IPR012340 Nucleic acid-binding, OB-fold
IPR015187 BRCA2, oligonucleotide/oligosaccharide-binding 1
IPR015188 BRCA2, oligonucleotide/oligosaccharide-binding 3
IPR015205 Tower
IPR015252 Breast cancer type 2 susceptibility protein, helical domain
IPR015525 Breast cancer type 2 susceptibility protein

PFAM

PF00634
PF09103
PF09104
PF09121
PF09169

PRINTS

PIRSF

PIRSF002397

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P51587