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.
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.
ETS translocation variant 4 (ETV4), also known as polyoma enhancer activator 3 (PEA3), is a member of the PEA3 subfamily of Ets transcription factors.
Probable G-protein coupled receptor 12 is a protein that in humans is encoded by the GPR12 gene.
Frizzled-6(Fz-6) is a protein that in humans is encoded by the FZD6 gene.
ATP-binding cassette sub-family G member 1 is a protein that in humans is encoded by the ABCG1 gene. It is a homolog of the well-known Drosophila gene white.
Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 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.
C-jun-amino-terminal kinase-interacting protein 4 is a scaffold protein that in humans is encoded by the SPAG9 gene.
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.
Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBG gene. TPBG is an antagonist of Wnt/β-catenin signalling pathway.
Disintegrin and metalloproteinase domain-containing protein 2 or Beta-fertilin is an enzyme that in humans is encoded by the ADAM2 gene.
Ankyrin repeat and FYVE domain-containing protein 1 is a protein that in humans is encoded by the ANKFY1 gene.
Dixin is a protein that in humans is encoded by the DIXDC1 gene. When active it stops cancer metastasis due to extreme stickiness, both in vitro and in vivo.
Seizure protein 6 homolog is a protein that in humans is encoded by the SEZ6 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 6 transmembrane segments, TPCN1 only contains two domains.
