Mutations in BRCA1 and BRCA2 have been linked to an elevated risk of young onset breast cancer which has been demonstrated to be due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. Unlike BRCA1, BRCA2 has not been linked to ovarian cancer. While BRCA1 mutations are typically microinsertions and point mutations, BRCA2 mutations are typically microdeletions. BRCA2 putatively functions as a tumor suppressor gene; however, its exact function has not been well characterized. The similarity and functional analysis of BRCA2 and BRCA1 proteins suggests that these proteins function in the same genetic pathway. BRCA1 and BRCA2 have transcriptional activation potential and the two proteins are associated with the activation of double-strand break repair and/or homologous recombination. The two proteins have been shown to coexist and colocalize in a biochemical complex.

This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability and acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as BASC for BRCA1-associated genome surveillance complex. This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complex. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants have been described for this gene but only some have had their full-length natures identified.

This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in multiple transcript variants encoding different isoforms.

The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm.

The protein encoded by this gene is expressed ubiquitously and at the highest level in testes and spermatogonia. The protein is localized within nuclei, and it is very similar in structure to two zinc finger proteins, AF10 and AF17. It is suggested that these proteins form a family of regulatory proteins. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.

This gene encodes a mitogen-activated kinase which localizes to the nucleus. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3 but sequence comparison suggests that the protein is not involved in the immune response. Homology to the Drosophila gene female sterile homeotic suggests that this human gene may be part of a signal transduction pathway involved in growth control.

This gene was identified based on its homology to the gene encoding the RING3 protein, a serine/threonine kinase. The gene localizes to 9q34, a region which contains several major histocompatibility complex (MHC) genes. The function of the encoded protein is not known.

The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.

Mammalian bombesin-like peptides (see MIM 137260) are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism, and behavior. They bind to G protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors include gastrin-releasing peptide receptor (MIM 305670), neuromedin B receptor (MIM 162341), and bombesin-like receptor-3 (BRS3) (Ohki-Hamazaki et al., 1997).[supplied by OMIM]

BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene.

The protein encoded by this gene shows sequence similarity to the human breast carcinoma metastasis suppressor (BRMS1) protein and the mammalian Sds3 (suppressor of defective silencing 3) proteins. This protein is a component of the mSin3a family of histone deacetylase complexes (HDAC).

This gene encodes one of the multiple subunits of the RNA polymerase III transcription factor complex required for transcription of genes with promoter elements upstream of the initiation site. The product of this gene, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with the TATA-binding protein.

The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described.

This gene encodes a protein of unknown function. The protein contains a bromodomain, a sequence motif often found in transcriptional coactivators, and localizes to the nucleus in testis and several other cell types.

This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Three alternatively spliced variants encoding three different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. A transcript encoding a fourth isoform has not yet been completely characterized.

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 2 bromodomains and multiple WD repeats, and the function of this protein is not known. This gene is located within the Down syndrome region-2 on chromosome 21. Alternative splicing of this gene generates 3 transcript variants diverging at the 3' ends.

The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Three alternatively spliced transcript variants that encode distinct isoforms have been identified.

This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint. Alternative splicing results in multiple transcript variants.

This gene encodes a member of the RecQ DEAH helicase family. The related human protein is both a DNA-dependent ATPase and a 5-prime-to-3-prime DNA helicase. The human protein interacts with the BRCT repeats of breast cancer, type 1 (BRCA1) in a bound complex which is important in the normal double-strand break repair function of the BRCA1 gene.

This gene was temporarily named bromodomain-containing 5 (Brd5) and was renamed bromodomain-containing 4 (Brd4).

involved in the DNA damage response and DNA repair [RGD]

may be involved in apoptosis of neuronal cells [RGD]

weakly activated by agonist dY-bombesin [RGD]

human homolog is a serine/threonine kinase; mutation of gene is associated with human cancers [RGD]

tumor suppression gene; involved in repair of double-strand DNA breaks (DSBs) by homologous recombination [RGD]

mouse homolog may act as a transcriptional regulator, possibly involved in regulation of mammary epithelial cell proliferation and lactation [RGD]