Dehydrogenase/reductase (SDR family) member 7B is an enzyme encoded by the DHRS7B gene in humans, found on chromosome 17p11.2. DHRS7B encodes a protein that is predicted to function in steroid hormone regulation. A deletion in the chromosomal region 17p11.2 has been associated with Smith-Magenis Syndrome, a genetic developmental disorder.
Gene
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 exons with no predicted alternate splice forms, resulting in an 1841 bp 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 (CCDC144NL) and Ubiquitin specific peptidase 22 (USP22). Downstream of DHSRS7B on the negative strand of chromosome 17p11.2 is the gene Transmembrane protein 11 (TMEM11), and on the positive strand is the gene Mitogen-activated protein kinase, kinase 3 (MAP2K3).
Gene expression
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 amino acids, a molecular weight of 35.1 kDa, and an isoelectric point of 9.867. There is one predicted transmembrane domain in the protein sequence, a large neutrally charged region spanning residues 18-38. No 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.
Sequence Function "VVV" Valine-rich region, unknown function "TGXXXGXG" NADP binding site "NXXG" Possible active site motif "DXXD" Adenine ring pocket motif "GXXXXXSS" Possible active site motif "SXYXXXK" Catalytic site, with upstream serine residue "LXNNXG" Conserved region, unknown function "NLS" N-glycosylation site
Interactions
In humans, DHRS7B has been shown to physically interact with other proteins such as Mediator complex subunit 19 (MED19) and Brain and reproductive expressed-modulator protein (BRE). MED19 was found to interact with DHRS7B through a two hybrid screening approach and plays a role as a co-activator in regulated transcription of most RNA polymerase II dependent genes. BRE is a component of the BRCA1-A complex, which recognizes Lys-63 linked ubiquitinated histones H2A and H2AX DNA lesion sites (identified using anti-tag coimmunoprecipitation). Other proteins interacting with DHRS7B have only been identified through text mining.
Homology
Orthologs
Conservation of the DHRS7B protein sequence has been observed highly in mammals; moderately in reptiles, birds, fish and amphibians; minimally in invertebrates, insects, and fungi.
Genus/Species Common name Accession # Sequence Length Sequence Identity Sequence Similarity Notes Homo sapiens Human NP_056325.2 325 aa 100% 100% DHRS7B Pan troglodytes Chimpanzee XP_511344.2 325 aa 99% 99% Mammal Pongo abelli Sumatran orangutan NP_001127381 325 aa 99% 99% Mammal Mustela putorius furo Domestic ferret AER97198 345 aa 88% 94% Mammal Canis familiaris Dog XP_536670 325 aa 87% 94% Mammal Gallus gallus Chicken XP_414804 309 aa 73% 87% Bird Anolis carolinensis Lizard XP_003226576 309 aa 68% 85% Reptile Salmo salar Salmon ACM08861 310 aa 64% 85% Fish Xenopus (silurana) tropicalis Western clawed frog NP_001072246 309 aa 68% 84% Amphibia Drosophila melanogaster Fruit fly NP_651717 326 aa 45% 63% Insect Strongylocentrotus purpuratus Purple sea urchin XP_790920 344 aa 34% 50% Invertebrate Saccharomyces cerevisiae S288C Yeast NP_013953 267 aa 33% 49% Fungi
Paralogs
Paralogs of DHRS7B are all in the SDR superfamily and conservation of the SDR functional motifs was identified in a multiple sequence alignment.
Common name Accession # Sequence Length Sequence Identity Sequence Similarity DHRS7B NP_056325.2 325 aa 100% 100% DHRS7C AA_147025.1 308 aa 46% 66% DHRS7 CAH56402 375 aa 37% 53% HBD1 AAA58352 343 aa 35% 56% RDH8 EAW84062 331 aa 34% 53% RDH16 AAC39922 317 aa 33% 53% KDSR NP002026 332 aa 31% 51% HSD11B1 AAK83653 292 aa 29% 50% DHRS9 AAH58883 319 aa 29% 50% RDH5 AAH28298 318 aa 30% 49%
Clinical significance
DHRS7B has been identified in the Smith-Magenis Syndrome region, where a deletion in this chromosomal region (17p11.2) causes a genetic developmental disorder. In breast cancer cells expressing CD44 and 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 leukocytes on peripheral lymphoid organs and inflammation sites. CD24 is associated with B-cells, epithelial cells, and dendritic cells, functioning as an adhesion molecule and shown to enhance a tumor cell's capability of metastasizing.
References