{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe studies characterize two mammalian ATP‐grasp enzymes—RIMKLA and RIMKLB—that catalyze the formation of neuroactive dipeptides. RIMKLA, which is expressed almost exclusively in the central nervous system, catalyzes the ATP‐dependent synthesis of N‐acetylaspartylglutamate (NAAG) from N‐acetylaspartate and l‐glutamate. In comparison, RIMKLB, sharing significant sequence identity with RIMKLA and expressed in both the CNS and testis, not only synthesizes NAAG but is also capable of producing β‑citrylglutamate. The enzymatic products were confirmed by mass spectrometry and nuclear magnetic resonance studies, consistent with their classification in the ATP‐grasp family of ligases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional evidence for a physiological role of these enzymes is provided by studies on RIMKLB in the testis. Immunolocalization in mouse tissue identified RIMKLB in Leydig cells, and a mutant mouse model carrying specific amino acid alterations in Rimklb (RimklbA29del, L30V) exhibited significant testicular hypoplasia alongside complete male infertility. These findings point to an important role in spermatogenesis that may be related to altered mammalian target of rapamycin (mTOR)/ribosomal protein S6 signaling within the seminiferous tubules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIt should be noted that although the original query mentioned RHOXF1-AS1, the provided abstracts do not address this antisense transcript. Instead, they focus on the functional elucidation of the RIMK homologues. Together, these studies reveal that while the CNS-associated RIMKLA is dedicated to NAAG synthesis, RIMKLB plays dual roles—contributing both to neuropeptide synthesis in the brain and to critical aspects of testicular development and spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "François Collard, Vincent Stroobant, Pedro Lamosa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular identification of N-acetylaspartylglutamate synthase and beta-citrylglutamate synthase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.152629"}], "href": "https://doi.org/10.1074/jbc.M110.152629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20657015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20657015"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Koji Maekura, Satoshi Tsukamoto, Michiko Hamada-Kanazawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rimklb mutation causes male infertility in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-84105-z"}], "href": "https://doi.org/10.1038/s41598-021-84105-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33633267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33633267"}]}]}]}