InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PALB2

Summary

InnateDB Protein

IDBP-20646.5

Last Modified

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

Gene Symbol

PALB2

Protein Name

partner and localizer of BRCA2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000261584

InnateDB Gene

IDBG-20644 (PALB2)

Protein Structure

UniProt Annotation

Function

Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilizes the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51. Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination. Via its WD repeats is proposed to scaffold a HR complex containing RAD51C and BRCA2 which is thought to play a role in HR-mediated DNA repair. Essential partner of BRCA2 that promotes the localization and stability of BRCA2. Also enables its recombinational repair and checkpoint functions of BRCA2. May act by promoting stable association of BRCA2 with nuclear structures, allowing BRCA2 to escape the effects of proteasome-mediated degradation. Binds DNA with high affinity for D loop, which comprises single-stranded, double-stranded and branched DNA structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with BRCA2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. {ECO:0000269PubMed:16793542, ECO:0000269PubMed:19369211, ECO:0000269PubMed:19423707, ECO:0000269PubMed:20871615, ECO:0000269PubMed:20871616, ECO:0000269PubMed:22941656, ECO:0000269PubMed:24141787, ECO:0000269PubMed:24485656}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:16793542}. Note=Colocalizes with BRCA2 in nuclear foci.

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:17287723, ECO:0000269PubMed:22241545}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Breast cancer susceptibility is strongly associated with PALB2 truncating mutations. Conversely, rare missense mutations do not strongly influence breast cancer risk (PubMed:22241545). {ECO:0000269PubMed:22241545}.Fanconi anemia complementation group N (FANCN) [MIM:610832]: 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:17200672}. Note=The disease is caused by mutations affecting the gene represented in this entry.Pancreatic cancer 3 (PNCA3) [MIM:613348]: 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:19264984}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 43 experimentally validated interaction(s) in this database.

Experimentally validated
Total	43 [view]
Protein-Protein	43 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0005515	protein binding

Biological Process

GO:0000724	double-strand break repair via homologous recombination
GO:0001756	somitogenesis
GO:0001833	inner cell mass cell proliferation
GO:0006281	DNA repair
GO:0007498	mesoderm development
GO:0009887	organ morphogenesis
GO:0036342	post-anal tail morphogenesis
GO:0043066	negative regulation of apoptotic process