Dehydrogenase/reductase (SDR family) member 7B is an enzyme encoded by the DHRS7B gene in humans, found on chromosome 17p11.2.[1] DHRS7B encodes a protein that is predicted to function in steroid hormone regulation.[2] [3] [4] A deletion in the chromosomal region 17p11.2 has been associated with Smith-Magenis Syndrome, a genetic developmental disorder.[5]
The DHRS7B gene is located on the positive strand of chromosome 17, beginning at position 21030258 and ending at position 21094836 (64579 bp).[6] DHRS7B contains seven exons with no predicted alternate splice forms, resulting in an 1841 bp mRNA product.[6] [7]
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).[8] 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).[8]
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.[9] [10]
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.[11] [12] There is one predicted transmembrane domain in the protein sequence, a large neutrally charged region spanning residues 18-38.[11] [12] No signal peptides have been identified in DHRS7B; cellular localization remains unclear.[13]
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.[14]
| 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 |
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).[15] 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.[16] 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).[17] Other proteins interacting with DHRS7B have only been identified through text mining.
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.[18]
| Genus/Species | Common Name | Accession # | Sequence Length | Sequence Identity | Sequence Similarity | Notes | |
|---|---|---|---|---|---|---|---|
| Homo sapiens | Human | NP_056325.2 https://www.ncbi.nlm.nih.gov/protein/NP_056325.2 | 325 aa | 100% | 100% | DHRS7B | |
| Pan troglodytes | Chimpanzee | XP_511344.2 https://www.ncbi.nlm.nih.gov/protein/114668638 | 325 aa | 99% | 99% | Mammal | |
| Pongo abelli | Sumatran orangutan | NP_001127381 https://www.ncbi.nlm.nih.gov/protein/NP_001127381.1 | 325 aa | 99% | 99% | Mammal | |
| Mustela putorius furo | Domestic ferret | AER97198 https://www.ncbi.nlm.nih.gov/protein/355683802 | 345 aa | 88% | 94% | Mammal | |
| Canis familiaris | Dog | XP_536670 https://www.ncbi.nlm.nih.gov/protein/73956279 | 325 aa | 87% | 94% | Mammal | |
| Gallus gallus | Chicken | XP_414804 https://www.ncbi.nlm.nih.gov/protein/50755579 | 309 aa | 73% | 87% | Bird | |
| Anolis carolinensis | Lizard | XP_003226576 https://www.ncbi.nlm.nih.gov/protein/327283695?report=genbank&log$=protalign&blast_rank=1&RID=SJ3KPVXC01S | 309 aa | 68% | 85% | Reptile | |
| Salmo salar | Salmon | ACM08861 https://www.ncbi.nlm.nih.gov/protein/221220400?report=genbank&log$=protalign&blast_rank=1&RID=SJ3ST4P8012 | 310 aa | 64% | 85% | Fish | |
| Xenopus (silurana) tropicalis | Western clawed frog | NP_001072246 https://www.ncbi.nlm.nih.gov/protein/NP_001072246.1 | 309 aa | 68% | 84% | Amphibia | |
| Drosophila melanogaster | Fruit fly | NP_651717 https://www.ncbi.nlm.nih.gov/protein/21358495?report=genbank&log$=protalign&blast_rank=5&RID=SJ40YTMT01S | 326 aa | 45% | 63% | Insect | |
| Strongylocentrotus purpuratus | Purple sea urchin | XP_790920 https://www.ncbi.nlm.nih.gov/protein/XP_790920 | 344 aa | 34% | 50% | Invertebrate | |
| Saccharomyces cerevisiae S288C | Yeast | NP_013953 https://www.ncbi.nlm.nih.gov/protein/NP_013953 | 267 aa | 33% | 49% | Fungi |
Paralogs of DHRS7B are all in the SDR superfamily and conservation of the SDR functional motifs was identified in a multiple sequence alignment.[18] [19]
| Common Name | Accession # | Sequence Length | Sequence Identity | Sequence Similarity | |
|---|---|---|---|---|---|
| DHRS7B | NP_056325.2 https://www.ncbi.nlm.nih.gov/protein/NP_056325.2 | 325 aa | 100% | 100% | |
| DHRS7C | AA_147025.1 https://www.ncbi.nlm.nih.gov/protein/AAI47025.1 | 308 aa | 46% | 66% | |
| CAH56402 https://www.ncbi.nlm.nih.gov/protein/CAH56402.1 | 375 aa | 37% | 53% | ||
| HBD1 | AAA58352 https://www.ncbi.nlm.nih.gov/protein/177198 | 343 aa | 35% | 56% | |
| RDH8 | EAW84062 https://www.ncbi.nlm.nih.gov/protein/EAW84062.1 | 331 aa | 34% | 53% | |
| RDH16 | AAC39922 https://www.ncbi.nlm.nih.gov/protein/3372592 | 317 aa | 33% | 53% | |
| KDSR | NP002026 https://www.ncbi.nlm.nih.gov/protein/4503817 | 332 aa | 31% | 51% | |
| HSD11B1 | AAK83653 https://www.ncbi.nlm.nih.gov/protein/AAK83653.1 | 292 aa | 29% | 50% | |
| DHRS9 | AAH58883 https://www.ncbi.nlm.nih.gov/protein/AAH58883.1 | 319 aa | 29% | 50% | |
| RDH5 | AAH28298 https://www.ncbi.nlm.nih.gov/protein/20271410 | 318 aa | 30% | 49% |
DHRS7B has been identified in the Smith-Magenis Syndrome region, where a deletion in this chromosomal region (17p11.2) causes a genetic developmental disorder.[4] In breast cancer cells expressing CD44 and CD24, DHRS7B expression was observed to be down regulated.[20] 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.[21]