Abhydrolase domain-containing protein 2 is a serine hydrolase enzyme that is strongly expressed in human spermatozoa. It is a key controller of sperm hyperactivation, which is a necessary step in allowing sperm to fertilize an egg. [5] It is encoded by the ABHD2 gene. [6]
In the presence of Progesterone (or Pregnenolone Sulfate, [7] ) it cleaves 2-arachidonoylglycerol (2AG) into glycerol and arachidonic acid (AA). [8] 2AG inhibits sperm calcium channel CatSper, and so when ABHD2 removes 2AG calcium flows into the cell through the CatSper channel, leading to hyperactivation. [8]
ABHD2 is inhibited by testosterone, (as well as hydrocortisone, and the plant triterpenoids lupeol and pristimerin) which may prevent premature hyperactivation. [7]
This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a very wide range of enzymes. Alternative splicing of this gene results in two transcript variants encoding the same protein. [6]
The ABHD2 gene is down regulated in the lungs of people with Emphysema. Analysis of ABHD2 deficiency in mice found a decrease in phosphatidylcholine levels. The mice developed emphysema which was attributed to an increase in macrophage infiltration, increased inflammatory cytokine levels, an imbalance of protease/anti-protease, and an increase in cell death. This research suggests that ABHD2 is important in maintaining the structural integrity of the lungs, and that disruption of phospholipid metabolism in the alveoli may lead to the development of emphysema. [9] Increased expression has also been seen in the lungs of smokers. [10]
ABHD2 is also expressed in atherosclerotic lesions. Expression has been found to be higher in patients with unstable angina than in patients with stable angina. [11]
Up-regulation of ABHD2 has been observed in cells transfected with Hepatitis B virus (HBV) DNA (HepG2.2.15 cells). Expression was down-regulated by the drug lamivudine, used in the treatment of hepatitis B. It has been suggested that ABHD2 has an important role in HBV propagation and could be a potential drug target in the treatment of hepatitis B. [12]
Suppression of ABHD2 has been linked to poor prognoses in ovarian cancer and resistance to platinum-based chemotherapy drugs. [13]
The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels that seem to be specific to sperm. As sperm encounter the more alkaline environment of the female reproductive tract, CatSper channels become activated by the altered ion concentration. These channels are required for proper fertilization. The study of these channels has been slow because they do not traffic to the cell membrane in many heterologous systems.
Human gene HSPA1B is an intron-less gene which encodes for the heat shock protein HSP70-2, a member of the Hsp70 family of proteins. The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous genes, HSPA1A and HSPA1L. HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the three prime untranslated region, heat shock 70kDa protein 1A, from HSPA1A, and heat shock 70kDa protein 1B, from HSPA1B. A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.
Four and a half LIM domains protein 1 is a protein that in humans is encoded by the FHL1 gene.
CD163 is a protein that in humans is encoded by the CD163 gene. CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex and in the absence of haptoglobin - with lower affinity - for hemoglobin alone. It also is a marker of cells from the monocyte/macrophage lineage. CD163 functions as innate immune sensor for gram-positive and gram-negative bacteria. The receptor was discovered in 1987.
Adiponectin receptor 1 (AdipoR1) is a protein which in humans is encoded by the ADIPOR1 gene. It is a member of the progestin and adipoQ receptor (PAQR) family, and is also known as PAQR1.
Frizzled-6(Fz-6) is a protein that in humans is encoded by the FZD6 gene.
Lysophosphatidic acid receptor 6, also known as LPA6, P2RY5 and GPR87, is a protein that in humans is encoded by the LPAR6 gene. LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).
In enzymology, an ADP-specific glucokinase also known as ADP-dependent glucokinase is an enzyme that catalyzes the chemical reaction
Cytochrome P450 2C18 is a protein that in humans is encoded by the CYP2C18 gene.
Hairy/enhancer-of-split related with YRPW motif protein 1 is a protein that in humans is encoded by the HEY1 gene.
Sal-like 1 (Drosophila), also known as SALL1, is a protein which in humans is encoded by the SALL1 gene. As the full name suggests, it is one of the human versions of the spalt (sal) gene known in Drosophila.
VAMP-Associated Protein A is a protein that in humans is encoded by the VAPA gene. Together with VAPB and VAPC it forms the VAP protein family. They are integral endoplasmic reticulum membrane proteins of the type II and are ubiquitous among eukaryotes.
Serine/threonine-protein kinase 16 is an enzyme that in humans is encoded by the STK16 gene.
Endomucin is a protein that in humans is encoded by the EMCN gene. Endomucin is a marker for endothelial cells and hematopoietic stem cells.
Ankyrin repeat and FYVE domain-containing protein 1 is a protein that in humans is encoded by the ANKFY1 gene.
Seizure protein 6 homolog is a protein that in humans is encoded by the SEZ6 gene.
Triokinase/FMN cyclase is an enzyme that in humans is encoded by the DAK gene.
Rho GTPase-activating protein 9 is an enzyme that in humans is encoded by the ARHGAP9 gene.
L-asparaginase is an enzyme that in humans is encoded by the ASRGL1 gene.
Two pore segment channel 1 (TPC1) is a human protein encoded by the TPCN1 gene. The protein encoded by this gene is an ion channel. In contrast to other calcium and sodium channels which have four homologous domains, each containing six transmembrane segments, TPCN1 only contains two domains.
