| 交叉反應 |
Human,
(predicted: Mouse, Rat, Chicken, Dog, Cow, Horse, Rabbit, )
|
| 產品介紹 |
background:
The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group B. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]
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. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. In concert with NPM1, regulates centrosome duplication.
Subunit:
Monomer and dimer. Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair. Interacts with DSS1. Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG. Interacts with WDR16. Interacts with USP11. Interacts with DMC1. Part of a trimeric complex containing BRCA1, BRCA2 and PALB2. Interacts with PALB2. Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein. Interacts with ROCK2 and NPM1.
Subcellular Location:
Nuclear protein.
Tissue Specificity:
Highest levels of expression in breast and thymus, with slightly lower levels in lung, ovary and spleen.
Post-translational modifications:
Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination-dependent repair during S phase and G2 by inhibiting RAD51 binding.
Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation.
DISEASE:
Defects in BRCA2 are a cause of susceptibility to breast cancer (BC). 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.
Defects in BRCA2 are the cause of pancreatic cancer type 2 (PNCA2) [MIM:613347]. It is 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.
Similarity:
Contains 8 BRCA2 repeats.
Database links:
Entrez Gene: 2187 Human
Omim: 300515 Human
SwissProt: Q8NB91 Human
Unigene: 554740 Human
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
BRCA2蛋白與DNA修復和重組有關， 乳腺癌易感基因其突變和家族性乳腺癌、卵巢癌的發(fā)病有關。
BRCA2是新近發(fā)現(xiàn)的一個抑癌基因，它在流行病學上與早期發(fā)現(xiàn)的BRCA1有許多相似之處。有學者發(fā)現(xiàn)：BRCA2在其它BRCA2突變的家族中也發(fā)現(xiàn)多發(fā)有結腸癌、肺癌、輸尿管癌、腦瘤、胰腺癌和白血病等。BRCA2突變家族中這種腫瘤的多樣性在其它研究中也有報道。
|
