DHRS7B

Dehydrogenase/reductase (SDR family) member 7B is an is_associated_with::enzyme encoded by the DHRS7B is_associated_with::gene in humans, found on is_associated_with::chromosome 17p11.2. DHRS7B encodes a protein that is predicted to function in is_associated_with::steroid hormone regulation. A deletion in the chromosomal region 17p11.2 has been associated with is_associated_with::Smith-Magenis Syndrome, a genetic developmental disorder.

Overview
The DHRS7B gene is located on the positive strand of chromosome 17, beginning at position 21030258 and ending at position 21094836 (64579 bp). DHRS7B contains seven is_associated_with::exons with no predicted alternate is_associated_with::splice forms, resulting in an 1841 bp is_associated_with::mRNA product.

Upstream of DHRS7B on the negative strand of chromosome 17p11.2 are the genes Coiled-coil domain containing 144 family, N-terminal-like (is_associated_with::CCDC144NL) and Ubiquitin specific peptidase 22 (is_associated_with::USP22). Downstream of DHSRS7B on the negative strand of chromosome 17p11.2 is the gene Transmembrane protein 11 (is_associated_with::TMEM11), and on the positive strand is the gene Mitogen-activated protein kinase, kinase 3 (is_associated_with::MAP2K3).

Gene expression
is_associated_with::Microarray and EST data indicates that the DHRS7B gene is highly expressed in the testes, thyroid, kidneys, and adipose tissues. There is moderate expression in the brain, pancreas, mammary glands, and ovaries. Finally, there is little expression in spleen, thymus, tonsils, bone marrow, and bladder.



Protein structure
The DHRS7B gene has a predicted protein product that is 325 is_associated_with::amino acids, a is_associated_with::molecular weight of 35.1 kDa, and an is_associated_with::isoelectric point of 9.867. There is one predicted is_associated_with::transmembrane domain in the protein sequence, a large neutrally charged region spanning residues 18-38. No is_associated_with::signal peptides have been identified in DHRS7B; cellular localization remains unclear.

DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR within the protein sequence. The following table identifies sequences in the protein and corresponding function.

Interactions
In humans, DHRS7B has been shown to physically interact with other proteins such as Mediator complex subunit 19 (is_associated_with::MED19) and Brain and reproductive expressed-modulator protein (BRE). MED19 was found to interact with DHRS7B through a is_associated_with::two hybrid screening approach and plays a role as a co-activator in regulated transcription of most is_associated_with::RNA polymerase II dependent genes. BRE is a component of the BRCA1-A complex, which recognizes Lys-63 linked is_associated_with::ubiquitinated is_associated_with::histones H2A and H2AX DNA lesion sites (identified using anti-tag is_associated_with::coimmunoprecipitation). Other proteins interacting with DHRS7B have only been identified through text-mining.

Orthologs
Conservation of the DHRS7B protein sequence has been observed highly in is_associated_with::mammals; moderately in is_associated_with::reptiles, is_associated_with::birds, is_associated_with::fish and is_associated_with::amphibians; minimally in is_associated_with::invertebrates, is_associated_with::insects, and is_associated_with::fungi.

Paralogs
is_associated_with::Paralogs of DHRS7B are all in the SDR superfamily and conservation of the SDR functional motifs was identified in a multiple sequence alignment.

Clinical significance
DHRS7B has been identified in the is_associated_with::Smith-Magenis Syndrome region, where a deletion in this chromosomal region (17p11.2) causes a genetic developmental disorder. In breast cancer cells expressing is_associated_with::CD44 and is_associated_with::CD24, DHRS7B expression was observed to be down regulated. CD44 is an antigen found on the surface of most cell types and functions as a receptor that binds tissue macromolecules. Additionally, it acts as an adhesion molecule for is_associated_with::leukocytes on peripheral lymphoid organs and inflammation sites. CD24 is associated with is_associated_with::B-cells, is_associated_with::epithelial cells, and is_associated_with::dendritic cells, functioning as an adhesion molecule and shown to enhance a tumor cell's capability of is_associated_with::metastasizing.