{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Research across diverse systems has revealed that CPA5 functions in several distinct biological contexts. Molecular and biochemical characterization of the human and mouse CPA5 gene shows that it encodes a metallocarboxypeptidase with specificity for cleaving substrates bearing C‐terminal hydrophobic residues. CPA5 is predominantly expressed in tissues such as testis, brain, and pituitary, where it may participate in the intracellular processing of neuropeptide precursors (for example, the non‐basic cleavage of proopiomelanocortin‐derived peptides)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the testis, CPA5 (together with the adjacent long non‐coding RNA Gm31453) is highly expressed during spermiogenesis; however, gene‐knockout studies in mice indicate that CPA5 is dispensable for normal spermatogenesis and male fertility, suggesting that its role in germ cell development may be limited to subtle, fine‐tuning regulatory functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of human cancer, proteomic analyses have demonstrated that CPA5 is detectable in non‐metastatic colorectal carcinoma cell lines and is absent in metastatic ones, implying that its loss may correlate with tumor progression and that CPA5 could serve as a potential biomarker for disease status."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Studies in zebrafish reveal that, in the absence of certain other carboxypeptidase isoforms, CPA5 is expressed specifically in mast cells and can serve as a lineage marker. Its expression has been shown to be regulated by key developmental pathways—including Notch signaling—and to delineate the mast cell lineage from erythromyeloid progenitors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In a completely different biological system, the protozoan parasite "}, {"type": "i", "children": [{"type": "t", "text": "Entamoeba histolytica"}]}, {"type": "t", "text": " expresses a cysteine protease designated CP‐A5. This enzyme has been implicated as a virulence factor that contributes to invasive behavior by mediating extracellular matrix remodeling – in part through the activation of host matrix metalloproteinases – thereby promoting tissue penetration during infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, candidate gene studies conducted in genomic regions implicated in neurodevelopment and imprinting have included CPA5 as one of several adjacent genes; however, the low and tissue‐restricted expression of CPA5 has precluded a definitive assessment of its imprinting status in these contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suwen Wei, Sonia Segura, Josep Vendrell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of three members of the human metallocarboxypeptidase gene family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112254200"}], "href": "https://doi.org/10.1074/jbc.M112254200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11836249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11836249"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Suwen Wei, Yun Feng, Elena Kalinina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuropeptide-processing carboxypeptidases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0024-3205(03)00386-2"}], "href": "https://doi.org/10.1016/s0024-3205(03"}, {"type": "t", "text": "00386-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12801587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12801587"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yang Zhou, Xiaona Zhang, Suping Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Predicted gene 31453 (Gm31453) and the gene encoding carboxypeptidase A5 (Cpa5) are not essential for spermatogenesis and male fertility in the mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Fertil Dev (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1071/RD20284"}], "href": "https://doi.org/10.1071/RD20284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33745502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33745502"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhang Ying-Tao, Geng Yi-Ping, Si Lu-Sheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic analysis of differentially expressed proteins between metastatic and non-metastatic human colorectal carcinoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Gastroenterol Hepatol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00042737-200507000-00006"}], "href": "https://doi.org/10.1097/00042737-200507000-00006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15947549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15947549"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "J Tristan Dobson, Jake Seibert, Evelyn M Teh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxypeptidase A5 identifies a novel mast cell lineage in the zebrafish providing new insight into mast cell fate determination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-03-145011"}], "href": "https://doi.org/10.1182/blood-2008-03-145011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18635811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18635811"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sahar I Da'as, Andrew J Coombs, Tugce B Balci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The zebrafish reveals dependence of the mast cell lineage on Notch signaling in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-10-385989"}], "href": "https://doi.org/10.1182/blood-2011-10-385989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22368273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22368273"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Srinivas Akula, Lars Hellman, Francesc Xavier Avilés, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of the mast cell expressed carboxypeptidase A3 and its structural and evolutionary relationship to other vertebrate carboxypeptidases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Comp Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dci.2021.104273"}], "href": "https://doi.org/10.1016/j.dci.2021.104273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34619175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34619175"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maya Huguenin, Rivka Bracha, Thanat Chookajorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic transcriptional gene silencing in Entamoeba histolytica: insight into histone and chromatin modifications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parasitology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0031182009991363"}], "href": "https://doi.org/10.1017/S0031182009991363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19849886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19849886"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Roman Thibeaux, Patrick Avé, Michèle Bernier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms6142"}], "href": "https://doi.org/10.1038/ncomms6142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25291063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25291063"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "E Bonora, E Bacchelli, E R Levy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001004"}], "href": "https://doi.org/10.1038/sj.mp.4001004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11920156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11920156"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "L Bentley, K Nakabayashi, D Monk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The imprinted region on human chromosome 7q32 extends to the carboxypeptidase A gene cluster: an imprinted candidate for Silver-Russell syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.40.4.249"}], "href": "https://doi.org/10.1136/jmg.40.4.249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12676894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12676894"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Takahiro Yamada, Kohzoh Mitsuya, Tomohiko Kayashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-flanking region at human chromosome 7q32."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2003.08.016"}], "href": "https://doi.org/10.1016/j.ygeno.2003.08.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14962666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14962666"}]}]}]}