{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9W0H3","uniProtkbId":"LDAH_DROME","entryAudit":{"firstPublicDate":"2015-06-24","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-05-01","entryVersion":157,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Drosophila melanogaster","commonName":"Fruit fly","taxonId":7227,"lineage":["Eukaryota","Metazoa","Ecdysozoa","Arthropoda","Altocrustacea","Allotriocarida","Hexapoda","Insecta","Pterygota","Neoptera","Eumetabola","Endopterygota","Aparaglossata","Panorpida","Diptera","Brachycera","Muscomorpha","Ephydroidea","Drosophilidae","Drosophila","Sophophora"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"}],"value":"Lipid droplet-associated hydrolase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"}],"value":"3.1.1.13"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"}],"value":"Lipid droplet-associated serine hydrolase"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30917324"},{"evidenceCode":"ECO:0000312","source":"FlyBase","id":"FBgn0035206"}],"value":"sturkopf"},"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"FlyBase","id":"FBgn0035206"}],"value":"CG9186"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27836991"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30917324"}],"value":"Probable serine lipid hydrolase associated with lipid droplets (By similarity). Appears to lack or have very low cholesterol esterase activity (By similarity) (PubMed:27836991). Appears to lack triglyceride lipase activity (PubMed:23525007, PubMed:27836991). Involved in cholesterol and triglyceride homeostasis; stimulates cellular triglyceride accumulation and cellular cholesterol release (By similarity). Involved in negatively regulating juvenile hormone (JH) and possibly, insulin signaling activities such as triacylglycerols (TAG) storage, and thereby plays a role in the endocrine regulation of organismal growth and survival (PubMed:30917324). Likely functions by enhancing the activity of the JH hydrolase enzymes Jheh1 and Jheh2 (PubMed:30917324). Required for lipid droplet positioning and fat storage (PubMed:23525007)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a cholesterol ester + H2O = cholesterol + a fatty acid + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:36403"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:16113"},{"database":"ChEBI","id":"CHEBI:17002"},{"database":"ChEBI","id":"CHEBI:28868"}],"ecNumber":"3.1.1.13","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:36404"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30917324"}],"value":"Interacts with the juvenile hormone hydrolase enzymes Jheh1 and Jheh2 (PubMed:30917324). Also interacts with Hmu, Cpr, Gp93 and Pvr (PubMed:30917324)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"}],"value":"Localizes to the endoplasmic reticulum in absence of lipid droplets and translocates to lipid droplets upon lipid storage induction"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27836991"}],"value":"Lipid droplet","id":"SL-0154"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30917324"}],"value":"Expressed in accessory glands"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"}],"value":"Expressed maternally and zygotically (PubMed:23525007). During embryonic stages 12-13, becomes restricted to the salivary glands (PubMed:23525007)"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30917324"}],"value":"Viable and fertile but displays phenotypes that appear to be the result of increased juvenile hormone (JH) and insulin/insulin-like growth factor (IIS) signaling (PubMed:30917324). For example, under nutritional stress shows reduced male survival, sensitivity toward oxidative stress, decreased locomotor activity, altered cuticular hydrocarbon (CHC) composition and desiccation protection, increased nuclear foxo levels and larvae are unable to adjust their developmental timing to their nutritional condition (PubMed:30917324). Six day old adults also display a significant reduction in triacylglycerol (TAG) storage levels (PubMed:30917324). In contrast, TAG levels in embryos and third-instar larvae are unaffected (PubMed:30917324)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30917324"}],"value":"'Sturkopf' means 'stubborn person' in German (PubMed:30917324). The name originates from mutant larvae which do not adjust their developmental timing to their nutritional conditions (PubMed:30917324)"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the AB hydrolase superfamily. LDAH family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8BVA5"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23525007"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27836991"}],"value":"The catalytic activity is unsure despite catalytic sites being conserved (PubMed:23525007, PubMed:27836991). Lacks cholesterol esterase activity when overexpressed in S2 cells (PubMed:27836991). The murine ortholog does have cholesterol esterase activity, although the activity is so low that it may be undetectable under certain experimental conditions or masked by other cellular cholesterol esterases (By similarity). Lacks lipolytic activity towards trioleoylglycerol, dioleoylglycerol or monooleoylglycerol when overexpressed in COS-7 cells or S2 cells (PubMed:23525007, PubMed:27836991)"}],"commentType":"CAUTION"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":307,"modifier":"EXACT"}},"description":"Lipid droplet-associated hydrolase","featureId":"PRO_0000433426"},{"type":"Transmembrane","location":{"start":{"value":166,"modifier":"EXACT"},"end":{"value":186,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":188,"modifier":"EXACT"},"end":{"value":208,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Region","location":{"start":{"value":157,"modifier":"EXACT"},"end":{"value":200,"modifier":"EXACT"}},"description":"Potential amphipathic helix required for binding to lipid 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