Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone.
-
ABHD2 acts as a progesterone-dependent monoacylglycerol lipase that depletes 2-AG from sperm plasma membrane, relieving CatSper inhibition and enabling calcium influx for sperm activation.
"ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane"
-
ABHD2 localizes to the human sperm flagellum and plasma membrane.
"ABHD2 is highly expressed in spermatozoa"
-
2-AG inhibits CatSper with IC50 of approximately 350 nM; removal of 2-AG by ABHD2 enables calcium influx.
"The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation"
Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase.
-
Recombinant ABHD2 has TAG lipase activity (1.14 +/- 0.11 umol/s/mg) and ester hydrolase activity against pNP acetate, butyrate, and palmitate substrates.
"This affinity purified recombinant hABHD2 protein fraction showed TAG lipase activity of 1.14±0.11 μmol/s·mg of protein against controls"
-
The catalytic triad of ABHD2 consists of Ser207, Asp345, His376 with Ser207 in the conserved GXSXG motif as the catalytic nucleophile.
"Sequence analysis of ABHD2 revealed the presence of conserved motifs G(205)XS(207)XG(209)"
Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2.
-
ABHD2 localizes to the ER membrane in somatic cells and regulates calcium release.
"pyrrophenone and KT195 inhibit cell death induced by A23187 and H2O2 by blocking the release of calcium from the endoplasmic reticulum and mitochondrial calcium uptake"
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods