LDAH_DROME
ID LDAH_DROME Reviewed; 307 AA.
AC Q9W0H3;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Lipid droplet-associated hydrolase {ECO:0000250|UniProtKB:Q8BVA5};
DE EC=3.1.1.- {ECO:0000250|UniProtKB:Q8BVA5};
DE AltName: Full=Lipid droplet-associated serine hydrolase {ECO:0000250|UniProtKB:Q8BVA5};
GN Name=sturkopf {ECO:0000303|PubMed:30917324,
GN ECO:0000312|FlyBase:FBgn0035206};
GN ORFNames=CG9186 {ECO:0000312|FlyBase:FBgn0035206};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Larva, and Pupae;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=23525007; DOI=10.1242/jcs.120493;
RA Thiel K., Heier C., Haberl V., Thul P.J., Oberer M., Lass A., Jackle H.,
RA Beller M.;
RT "The evolutionarily conserved protein CG9186 is associated with lipid
RT droplets, required for their positioning and for fat storage.";
RL J. Cell Sci. 126:2198-2212(2013).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27836991; DOI=10.1194/jlr.m072538;
RA Kory N., Grond S., Kamat S.S., Li Z., Krahmer N., Chitraju C., Zhou P.,
RA Froehlich F., Semova I., Ejsing C., Zechner R., Cravatt B.F.,
RA Farese R.V. Jr., Walther T.C.;
RT "Mice lacking lipid droplet-associated hydrolase, a gene linked to human
RT prostate cancer, have normal cholesterol ester metabolism.";
RL J. Lipid Res. 58:226-235(2017).
RN [6]
RP FUNCTION, INTERACTION WITH HMU, CPR, GP93, PVR, JHEH1 AND JHEH2, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30917324; DOI=10.1016/j.celrep.2019.02.110;
RA Werthebach M., Stewart F.A., Gahlen A., Mettler-Altmann T., Akhtar I.,
RA Maas-Enriquez K., Droste A., Eichmann T.O., Poschmann G., Stuehler K.,
RA Beller M.;
RT "Control of Drosophila Growth and Survival by the Lipid Droplet-Associated
RT Protein CG9186/Sturkopf.";
RL Cell Rep. 26:3726-3740(2019).
CC -!- FUNCTION: Probable serine lipid hydrolase associated with lipid
CC droplets (By similarity). Appears to lack cholesterol esterase activity
CC (PubMed:27836991). Appears to lack triglyceride lipase activity
CC (PubMed:23525007, PubMed:27836991). Involved in negatively regulating
CC juvenile hormone (JH) and possibly, insulin signaling activities such
CC as triacylglycerols (TAG) storage, and thereby plays a role in the
CC endocrine regulation of organismal growth and survival
CC (PubMed:30917324). Likely functions by enhancing the activity of the JH
CC hydrolase enzymes Jheh1 and Jheh2 (PubMed:30917324). Required for lipid
CC droplet positioning and fat storage (PubMed:23525007).
CC {ECO:0000250|UniProtKB:Q8BVA5, ECO:0000269|PubMed:23525007,
CC ECO:0000269|PubMed:27836991, ECO:0000269|PubMed:30917324}.
CC -!- SUBUNIT: Interacts with the juvenile hormone hydrolase enzymes Jheh1
CC and Jheh2 (PubMed:30917324). Also interacts with Hmu, Cpr, Gp93 and Pvr
CC (PubMed:30917324). {ECO:0000269|PubMed:30917324}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:23525007,
CC ECO:0000269|PubMed:27836991}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23525007}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to the endoplasmic reticulum in absence
CC of lipid droplets and translocates to lipid droplets upon lipid storage
CC induction. {ECO:0000269|PubMed:23525007}.
CC -!- TISSUE SPECIFICITY: Expressed in accessory glands.
CC {ECO:0000269|PubMed:30917324}.
CC -!- DEVELOPMENTAL STAGE: Expressed maternally and zygotically
CC (PubMed:23525007). During embryonic stages 12-13, becomes restricted to
CC the salivary glands (PubMed:23525007). {ECO:0000269|PubMed:23525007}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile but displays phenotypes that
CC appear to be the result of increased juvenile hormone (JH) and
CC insulin/insulin-like growth factor (IIS) signaling (PubMed:30917324).
CC For example, under nutritional stress shows reduced male survival,
CC sensitivity toward oxidative stress, decreased locomotor activity,
CC altered cuticular hydrocarbon (CHC) composition and desiccation
CC protection, increased nuclear foxo levels and larvae are unable to
CC adjust their developmental timing to their nutritional condition
CC (PubMed:30917324). Six day old adults also display a significant
CC reduction in triacylglycerol (TAG) storage levels (PubMed:30917324). In
CC contrast, TAG levels in embryos and third-instar larvae are unaffected
CC (PubMed:30917324). {ECO:0000269|PubMed:30917324}.
CC -!- MISCELLANEOUS: 'Sturkopf' means 'stubborn person' in German
CC (PubMed:30917324). The name originates from mutant larvae which do not
CC adjust their developmental timing to their nutritional conditions
CC (PubMed:30917324). {ECO:0000269|PubMed:30917324}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. LDAH family.
CC {ECO:0000305}.
CC -!- CAUTION: The catalytic activity is unsure despite catalytic sites being
CC conserved (PubMed:23525007, PubMed:27836991). Lacks cholesterol
CC esterase activity when overexpressed in S2 cells (PubMed:27836991).
CC Lack lipolytic activity towards trioleoylglycerol, dioleoylglycerol or
CC monooleoylglycerol when overexpressed in COS-7 cells or S2 cells
CC (PubMed:23525007, PubMed:27836991). {ECO:0000269|PubMed:23525007,
CC ECO:0000269|PubMed:27836991}.
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DR EMBL; AE014296; AAF47473.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11470.1; -; Genomic_DNA.
DR EMBL; AY061530; AAL29078.1; -; mRNA.
DR RefSeq; NP_612097.1; NM_138253.2.
DR RefSeq; NP_728590.1; NM_167867.2.
DR AlphaFoldDB; Q9W0H3; -.
DR STRING; 7227.FBpp0072611; -.
DR ESTHER; drome-CG9186; LIDHydrolase.
DR PaxDb; Q9W0H3; -.
DR PRIDE; Q9W0H3; -.
DR DNASU; 38150; -.
DR EnsemblMetazoa; FBtr0072727; FBpp0072611; FBgn0035206.
DR EnsemblMetazoa; FBtr0072728; FBpp0072612; FBgn0035206.
DR GeneID; 38150; -.
DR KEGG; dme:Dmel_CG9186; -.
DR UCSC; CG9186-RA; d. melanogaster.
DR CTD; 38150; -.
DR FlyBase; FBgn0035206; sturkopf.
DR VEuPathDB; VectorBase:FBgn0035206; -.
DR eggNOG; KOG3975; Eukaryota.
DR GeneTree; ENSGT00390000009688; -.
DR HOGENOM; CLU_018394_2_1_1; -.
DR InParanoid; Q9W0H3; -.
DR OMA; PVWVIGH; -.
DR OrthoDB; 1163030at2759; -.
DR PhylomeDB; Q9W0H3; -.
DR BioGRID-ORCS; 38150; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 38150; -.
DR PRO; PR:Q9W0H3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035206; Expressed in capitellum (Drosophila) and 27 other tissues.
DR Genevisible; Q9W0H3; DM.
DR GO; GO:0012505; C:endomembrane system; HDA:FlyBase.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IDA:FlyBase.
DR GO; GO:0016298; F:lipase activity; IEA:InterPro.
DR GO; GO:0017171; F:serine hydrolase activity; HDA:FlyBase.
DR GO; GO:0034389; P:lipid droplet organization; IMP:FlyBase.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR GO; GO:0045928; P:negative regulation of juvenile hormone metabolic process; IDA:UniProtKB.
DR GO; GO:0010883; P:regulation of lipid storage; IMP:FlyBase.
DR GO; GO:0030730; P:sequestering of triglyceride; IMP:FlyBase.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR019363; LDAH.
DR PANTHER; PTHR13390; PTHR13390; 1.
DR Pfam; PF10230; LIDHydrolase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Hydrolase; Lipid droplet; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..307
FT /note="Lipid droplet-associated hydrolase"
FT /id="PRO_0000433426"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 157..200
FT /note="Required for binding to lipid droplets"
FT /evidence="ECO:0000269|PubMed:27836991"
FT ACT_SITE 119
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 254
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9H6V9"
FT ACT_SITE 283
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9H6V9"
SQ SEQUENCE 307 AA; 35736 MW; 3CA138D097F8308C CRC64;
MQEAYVNINS IPTHIFTWGR WIEETITEKE IVICITGNPG LPGFYTEFAG TLQKELGDLP
VWVIGHAGHD DPPEASIREV PQLSGNEELF NLDGQIRHKI AFIEKYVPSD VKIHLIGHSI
GAWMILQLLE NERIRSRIQK CYMLFPTVER MMESPNGWVF TKVAMPLYSV FGYIFFSFFN
FLPVWLRLML IQIYFLIFSI PRQFLGTALK YSKPSVAEKV VFLADDEMAR VRGIQREIVE
QNLDLLKFYY GTTDGWVPIS YYDQLKKDYP KVDAQLDTKK IDHAFVLRHS QPMAVIVRDM
IQQHRRV
