{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T15:41:49Z","timestamp":1772034109059,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p><jats:italic>Entamoeba\u00a0histolytica<\/jats:italic> is an intestinal protist parasite that causes amoebiasis, a major source of morbidity and mortality in developing countries. Phosphoinositides are involved in signalling systems that have a role in invasion and pathogenesis of this parasite. Phosphatidylinositol 4\u2010phosphate 5\u2010kinase (PIP5K) catalyses the generation of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P<jats:sub>2<\/jats:sub>), a key species of phosphoinositide that regulates various cellular processes. However, phosphatidylinositol phosphate kinase (PIPK) family of enzymes have not been characterized in <jats:italic>E.\u00a0histolytica<\/jats:italic>. Here, we report the identification and characterization of type I PIPK (EhPIPKI) of <jats:italic>E.\u00a0histolytica<\/jats:italic>. Computational analysis revealed homologs of type I and III PIPK family in <jats:italic>E.\u00a0histolytica<\/jats:italic> and the absence of type II PIPK. In spite of low overall sequence identity, the kinase domain was found to be highly conserved. Interestingly, a unique insertion of a tandem repeat motif was observed in EhPIPKI distinguishing it from existing PIPKs of other organisms. Substrate profiling showed that EhPIPKI could phosphorylate at third and fifth hydroxyl positions of phosphatidylinositols, though the predominant substrate was phosphatidylinositol 4\u2010phosphate (PtdIns(4)P). Furthermore, EhPIPKI underwent intracellular cleavage close to the amino\u2010terminal, generating two\u00a0distinct fragments Nter\u2010EhPIPKI (27p) and Cter\u2010EhPIPKI (47p). Immunofluorescence and cellular fractionation revealed that the full\u2010length EhPIPKI and the Cter\u2010EhPIPKI containing carboxyl\u2010terminal activation loop were present in the plasma membrane while the Nter\u2010EhPIPKI was observed in the cytosolic region. In conclusion, <jats:italic>E.\u00a0histolytica<\/jats:italic> has a single EhPIPKI gene that displays novel properties of post\u2010translational processing, the presence of a repeat domain and substrate specificity not observed in any PIPK enzyme so far.<\/jats:p>","DOI":"10.1111\/febs.14804","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T08:58:48Z","timestamp":1551949128000},"page":"2216-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PtdIns(4,5)P<sub>2<\/sub> is generated by a novel phosphatidylinositol 4\u2010phosphate 5\u2010kinase in the protist parasite <i>Entamoeba\u00a0histolytica<\/i>"],"prefix":"10.1111","volume":"286","author":[{"given":"Shalini","family":"Sharma","sequence":"first","affiliation":[{"name":"School of Life Sciences Jawaharlal Nehru University New Delhi 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