ABHD2 Membrane Protein Introduction

Introduction of ABHD2

ABHD2, the abbreviation of Abhydrolase domain-containing protein 2, is encoded by the ABHD2 gene. It is a serine hydrolase enzyme that is strongly expressed in human spermatozoa. It is a key controller of sperm hyperactivation, which is a critical step in allowing sperm to fertilize an egg. This protein contains an alpha/beta hydrolase fold, which is a catalytic domain found in different kinds of enzymes. This gene can be spliced into two transcript variants which encode the same proteins. It’s related to emphysema, and atherosclerotic lesions.

Function of ABHD2 Membrane Protein

ABHD2, the full name is abhydrolase domain-containing protein 2. It’s able to cleave 2-arachidonoylglycerol (2AG) into glycerol and arachidonic acid (AA), in the presence of progesterone or pregnenolone sulfate. 2AG can suppress sperm calcium channel-CatSper. When ABHD2 induces 2AG calcium flows into the cell via the CatSper channel, it can lead to hyperactivation. ABHD2 can be inhibited by testosterone, hydrocortisone, pristimerin and plant triterpenoids lupeol which may prevent premature hyperactivation. The acylglycerol lipase can catalyze the hydrolysis of endocannabinoid AG from cell membranes, which is dependent on progesterone. ABHD2 is highly expressed in spermatozoa, where it acts as a progesterone receptor to activate the acylglycerol lipase activity, mediating degradation of 1AG and 2AG to glycerol and AA. In addition, ABHD2 has a critical role in sperm capacitation in response to progesterone through mediating degradation of 2AG. It’s a suppressor of the sperm calcium channel CatSper, and it can result in calcium influx via CatSper and sperm activation. It may also play a role in smooth muscle cells migration.

Fig.1 ABHD2 regulates Ca²⁺ influx in human flagellum and involved in mouse acrosome reaction (Miller, 2016)

Application of ABHD2 Membrane Protein in Literature

1. Mannowetz N., et al. Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids. Proc Natl Acad Sci U S A. 2017, 114(22): 5743-5748. PubMed ID: 28507119
   
   

   This article indicates that endogenous steroids and plant triterpenoids can influence CatSper activation via modulation of ABHD2.

2. Miller M.R., et al. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone. Science. 2016, 352(6285): 555-9. PubMed ID: 26989199
   
   

   This article shows that progesterone-activated endocannabinoid depletion by ABHD2 is a common mechanism.

3. Obinata D., et al. Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration. Eur J Cancer. 2016, 57: 39-49. PubMed ID: 26854828
   
   

   This study indicates that ABHD2 is a new androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy and is a novel target for diagnosis and treatment of prostate cancer.

4. Ding X.R., et al. Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs. Pharmacogenomics J. 2008, 8(1): 61-70. PubMed ID: 17505500
   
   

   This article demonstrates that ABHD2 and EREG are critical for HBV propagation and provides strong evidence that these proteins could be used as promising targets for anti-HBV drugs.

5. Johansson F.K., et al. Expression analysis of genes involved in brain tumor progression driven by retroviral insertional mutagenesis in mice. Oncogene. 2005, 24(24): 3896-905. PubMed ID: 15750623
   
   

   This article shows that ABHD2 plays a critical role in brain tumor progression.

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Reference

1. Miller M R, et al. (2016). Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone. Science. 352(6285): 555-9.

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