SG ID

SG00000116 

UniProt Accession

F1R8E8_DANRE;F1R8E8;  

Theoretical PI

6.06  

Molecular Weight

317245 Da  

Genbank Nucleotide ID

CR536612; CR628361;  

Genbank Protein ID

 

Gene Name

brca2 

Gene Synonyms/Alias

 

Protein Name

 

Protein Synonyms/Alias

SubName: Uncharacterized protein 

Danio rerio (Zebrafish) (Brachydanio rerio) 

7955 

Temporarily unavailable 

The information of related literatures

1. A. Rodriguez-Mari, C. Wilson, T. A. Titus, C. Canestro, R. A. BreMiller, Y. L. Yan, I. Nanda, A. Johnston, J. P. Kanki, E. M. Gray, X. He, J. Spitsbergen, D. Schindler and J. H. Postlethwait (2011) Roles of brca2 (fancd1) in oocyte nuclear architecture, gametogenesis, gonad tumors, and genome stability in zebrafish. PLoS Genet 7(3): e1001357. 

Abstract
Mild mutations in BRCA2 (FANCD1) cause Fanconi anemia (FA) when homozygous, while severe mutations cause common cancers including breast, ovarian, and prostate cancers when heterozygous. Here we report a zebrafish brca2 insertional mutant that shares phenotypes with human patients and identifies a novel brca2 function in oogenesis. Experiments showed that mutant embryos and mutant cells in culture experienced genome instability, as do cells in FA patients. In wild-type zebrafish, meiotic cells expressed brca2; and, unexpectedly, transcripts in oocytes localized asymmetrically to the animal pole. In juvenile brca2 mutants, oocytes failed to progress through meiosis, leading to female-to-male sex reversal. Adult mutants became sterile males due to the meiotic arrest of spermatocytes, which then died by apoptosis, followed by neoplastic proliferation of gonad somatic cells that was similar to neoplasia observed in ageing dead end (dnd)-knockdown males, which lack germ cells. The construction of animals doubly mutant for brca2 and the apoptotic gene tp53 (p53) rescued brca2-dependent sex reversal. Double mutants developed oocytes and became sterile females that produced only aberrant embryos and showed elevated risk for invasive ovarian tumors. Oocytes in double-mutant females showed normal localization of brca2 and pou5f1 transcripts to the animal pole and vasa transcripts to the vegetal pole, but had a polarized rather than symmetrical nucleus with the distribution of nucleoli and chromosomes to opposite nuclear poles; this result revealed a novel role for Brca2 in establishing or maintaining oocyte nuclear architecture. Mutating tp53 did not rescue the infertility phenotype in brca2 mutant males, suggesting that brca2 plays an essential role in zebrafish spermatogenesis. Overall, this work verified zebrafish as a model for the role of Brca2 in human disease and uncovered a novel function of Brca2 in vertebrate oocyte nuclear architecture. PMID: [21483806] 

2. H. R. Shive, R. R. West, L. J. Embree, M. Azuma, R. Sood, P. Liu and D. D. Hickstein (2010) brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proc Natl Acad Sci U S A 107(45): 19350-5. 

Abstract
Humans with inherited mutations in BRCA2 are at increased risk for developing breast and ovarian cancer; however, the relationship between BRCA2 mutation and these cancers is not understood. Studies of Brca2 mutation by gene targeting in mice are limited, given that homozygous Brca2 mutation typically leads to early embryonic lethality. We established a zebrafish line with a nonsense mutation in brca2 exon 11 (brca2(Q658X)), a mutation similar in location and type to BRCA2 mutations found in humans with hereditary breast and ovarian cancer. brca2(Q658X) homozygous zebrafish are viable and survive to adulthood; however, juvenile homozygotes fail to develop ovaries during sexual differentiation. Instead, brca2(Q658X) homozygotes develop as infertile males with meiotic arrest in spermatocytes. Germ cell migration to the embryonic gonadal ridge is unimpaired in brca2(Q658X) homozygotes; thus, failure of ovarian development is not due to defects in early establishment of the embryonic gonad. Homozygous tp53 mutation rescues ovarian development in brca2(Q658X) homozygous zebrafish, reflecting the importance of germ cell apoptosis in gonad morphogenesis. Adult brca2(Q658X) homozygous zebrafish are predisposed to testicular neoplasias. In addition, tumorigenesis in multiple tissues is significantly accelerated in combination with homozygous tp53 mutation in both brca2(Q658X) homozygous and brca2(Q658X) heterozygous zebrafish. These studies reveal critical roles for brca2 in ovarian development and tumorigenesis in reproductive tissues. PMID: [20974951] 

Figures for illustrating the function of this protein/gene

Function

 

Subcellular Location

 

Tissue Specificity

 

Gene Ontology

GO ID	GO term	Evidence
GO:0005634	C:nucleus	IEA:InterPro.
GO:0003697	F:single-stranded DNA binding	IEA:InterPro.
GO:0000724	P:double-strand break repair via homologous recombination	IEA:InterPro.
GO:0008585	P:female gonad development	IMP:ZFIN.
GO:0007090	P:regulation of S phase of mitotic cell cycle	IEA:InterPro.
GO:0007283	P:spermatogenesis	IMP:ZFIN.

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Interpro

IPR015525;    BRCA2.
IPR015187;    BRCA2_OB_1.
IPR015188;    BRCA2_OB_3.
IPR002093;    BRCA2_repeat.
IPR011370;    DNA_recomb/repair_BRCA2.
IPR015252;    DNA_recomb/repair_BRCA2_hlx.
IPR016027;    NA-bd_OB-fold-like.
IPR015205;    Tower.
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Pfam

PF09169;    BRCA-2_helical;    1.
PF09103;    BRCA-2_OB1;    1.
PF09104;    BRCA-2_OB3;    1.
PF00634;    BRCA2;    9.
PF09121;    Tower;    1.
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SMART

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PROSITE

PS50138;    BRCA2_REPEAT;    12.
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PRINTS

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Created Date

18-Oct-2012 

Record Type

Experiment identified 

Protein sequence Annotation

Nucleotide Sequence

Length: bp   Go to nucleotide: FASTA

Protein Sequence

Length: 2874 bp   Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt

Gene Symbol

Ref Databases

Other Protein-Protein interaction resources

String database  

UniProt

Gene Symbol

Ref Databases

View Microarray data

Temporarily unavailable 

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