NCEH1_MOUSE
ID NCEH1_MOUSE Reviewed; 408 AA.
AC Q8BLF1; Q69ZL0; Q8BZK3;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Neutral cholesterol ester hydrolase 1;
DE Short=NCEH;
DE EC=3.1.1.- {ECO:0000269|PubMed:18782767, ECO:0000269|PubMed:20625037};
DE AltName: Full=Acetylalkylglycerol acetylhydrolase {ECO:0000305};
DE Short=2-acetyl MAGE hydrolase {ECO:0000250|UniProtKB:Q6PIU2};
DE EC=3.1.1.71 {ECO:0000269|PubMed:20625037};
DE AltName: Full=Arylacetamide deacetylase-like 1;
DE AltName: Full=Chlorpyrifos oxon-binding protein;
DE Short=CPO-BP;
GN Name=Nceh1; Synonyms=Aadacl1, Kiaa1363;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic intestine;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Diencephalon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP ACTIVITY REGULATION, AND GLYCOSYLATION.
RX PubMed=12740587; DOI=10.1038/nbt826;
RA Leung D., Hardouin C., Boger D.L., Cravatt B.F.;
RT "Discovering potent and selective reversible inhibitors of enzymes in
RT complex proteomes.";
RL Nat. Biotechnol. 21:687-691(2003).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15840715; DOI=10.1073/pnas.0501915102;
RA Nomura D.K., Leung D., Chiang K.P., Quistad G.B., Cravatt B.F.,
RA Casida J.E.;
RT "A brain detoxifying enzyme for organophosphorus nerve poisons.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:6195-6200(2005).
RN [6]
RP FUNCTION, ACTIVE SITE, AND TISSUE SPECIFICITY.
RX PubMed=16978018; DOI=10.1021/tx060117m;
RA Nomura D.K., Durkin K.A., Chiang K.P., Quistad G.B., Cravatt B.F.,
RA Casida J.E.;
RT "Serine hydrolase KIAA1363: toxicological and structural features with
RT emphasis on organophosphate interactions.";
RL Chem. Res. Toxicol. 19:1142-1150(2006).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18782767; DOI=10.1074/jbc.m802686200;
RA Okazaki H., Igarashi M., Nishi M., Sekiya M., Tajima M., Takase S.,
RA Takanashi M., Ohta K., Tamura Y., Okazaki S., Yahagi N., Ohashi K.,
RA Amemiya-Kudo M., Nakagawa Y., Nagai R., Kadowaki T., Osuga J.,
RA Ishibashi S.;
RT "Identification of neutral cholesterol ester hydrolase, a key enzyme
RT removing cholesterol from macrophages.";
RL J. Biol. Chem. 283:33357-33364(2008).
RN [8]
RP FUNCTION.
RX PubMed=18164358; DOI=10.1016/j.taap.2007.11.021;
RA Nomura D.K., Fujioka K., Issa R.S., Ward A.M., Cravatt B.F., Casida J.E.;
RT "Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism
RT and organophosphate detoxification.";
RL Toxicol. Appl. Pharmacol. 228:42-48(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20625037; DOI=10.1194/jlr.m004259;
RA Buchebner M., Pfeifer T., Rathke N., Chandak P.G., Lass A., Schreiber R.,
RA Kratzer A., Zimmermann R., Sattler W., Koefeler H., Froehlich E.,
RA Kostner G.M., Birner-Gruenberger R., Chiang K.P., Haemmerle G., Zechner R.,
RA Levak-Frank S., Cravatt B., Kratky D.;
RT "Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages
RT but unchanged in macrophages lacking KIAA1363.";
RL J. Lipid Res. 51:2896-2908(2010).
CC -!- FUNCTION: Hydrolyzes 2-acetyl monoalkylglycerol ether (1-O-alkyl-2-
CC acetyl-sn-glycerol), the penultimate precursor of the pathway for de
CC novo synthesis of platelet-activating factor (PubMed:18164358,
CC PubMed:20625037). May be responsible for the hydrolysis of cholesterol
CC esters (such as cholesteryl (9Z-octadecenoate)) in macrophages
CC (PubMed:18782767). Also involved in organ detoxification by hydrolyzing
CC exogenous organophosphorus compounds (PubMed:15840715, PubMed:16978018,
CC PubMed:18164358). {ECO:0000269|PubMed:15840715,
CC ECO:0000269|PubMed:16978018, ECO:0000269|PubMed:18164358,
CC ECO:0000269|PubMed:18782767, ECO:0000269|PubMed:20625037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-O-alkyl-2-acetyl-sn-glycerol + H2O = 1-O-alkyl-sn-glycerol
CC + acetate + H(+); Xref=Rhea:RHEA:11552, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15850, ChEBI:CHEBI:16291,
CC ChEBI:CHEBI:30089; EC=3.1.1.71;
CC Evidence={ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11553;
CC Evidence={ECO:0000269|PubMed:20625037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-
CC glycerol + acetate + H(+); Xref=Rhea:RHEA:38563, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:34115,
CC ChEBI:CHEBI:75936; Evidence={ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564;
CC Evidence={ECO:0000269|PubMed:20625037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cholesterol ester + H2O = a fatty acid + cholesterol + H(+);
CC Xref=Rhea:RHEA:36403, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17002, ChEBI:CHEBI:28868;
CC Evidence={ECO:0000269|PubMed:18782767, ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36404;
CC Evidence={ECO:0000305|PubMed:20625037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate +
CC cholesterol + H(+); Xref=Rhea:RHEA:33875, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:46898; Evidence={ECO:0000269|PubMed:18782767,
CC ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000305|PubMed:20625037};
CC -!- ACTIVITY REGULATION: Inhibited by bulky trifluoromethyl ketones.
CC {ECO:0000269|PubMed:12740587}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.2 for cholesterol ester hydrolysis.
CC {ECO:0000269|PubMed:18782767};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6PIU2};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q6PIU2}.
CC Microsome {ECO:0000269|PubMed:18782767}.
CC -!- TISSUE SPECIFICITY: Present in brain, heart, kidney, lung, spinal cord
CC and testis but not liver (at protein level). Expressed in peritoneal
CC macrophages and kidney. {ECO:0000269|PubMed:16978018,
CC ECO:0000269|PubMed:18782767}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12740587}.
CC -!- DISRUPTION PHENOTYPE: Mice are phenotypically normal but more sensitive
CC to organophosphorus insecticide toxicity.
CC {ECO:0000269|PubMed:15840715}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32436.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK173158; BAD32436.1; ALT_INIT; mRNA.
DR EMBL; AK034339; BAC28680.1; -; mRNA.
DR EMBL; AK045363; BAC32327.1; -; mRNA.
DR EMBL; AK135837; BAE22685.1; -; mRNA.
DR EMBL; BC082569; AAH82569.1; -; mRNA.
DR CCDS; CCDS17271.1; -.
DR RefSeq; NP_848887.1; NM_178772.3.
DR AlphaFoldDB; Q8BLF1; -.
DR SMR; Q8BLF1; -.
DR BioGRID; 235704; 18.
DR IntAct; Q8BLF1; 1.
DR MINT; Q8BLF1; -.
DR STRING; 10090.ENSMUSP00000045864; -.
DR BindingDB; Q8BLF1; -.
DR ChEMBL; CHEMBL5428; -.
DR SwissLipids; SLP:000000319; -.
DR ESTHER; mouse-Q8BLF1; Arylacetamide_deacetylase.
DR MEROPS; S09.992; -.
DR GlyConnect; 2560; 5 N-Linked glycans (1 site).
DR GlyGen; Q8BLF1; 3 sites, 5 N-linked glycans (1 site).
DR iPTMnet; Q8BLF1; -.
DR PhosphoSitePlus; Q8BLF1; -.
DR SwissPalm; Q8BLF1; -.
DR EPD; Q8BLF1; -.
DR jPOST; Q8BLF1; -.
DR MaxQB; Q8BLF1; -.
DR PaxDb; Q8BLF1; -.
DR PeptideAtlas; Q8BLF1; -.
DR PRIDE; Q8BLF1; -.
DR ProteomicsDB; 252648; -.
DR Antibodypedia; 33731; 114 antibodies from 23 providers.
DR DNASU; 320024; -.
DR Ensembl; ENSMUST00000046515; ENSMUSP00000045864; ENSMUSG00000027698.
DR GeneID; 320024; -.
DR KEGG; mmu:320024; -.
DR UCSC; uc008otl.1; mouse.
DR CTD; 57552; -.
DR MGI; MGI:2443191; Nceh1.
DR VEuPathDB; HostDB:ENSMUSG00000027698; -.
DR eggNOG; KOG1515; Eukaryota.
DR GeneTree; ENSGT00940000156699; -.
DR HOGENOM; CLU_012494_12_0_1; -.
DR InParanoid; Q8BLF1; -.
DR OMA; ISDPWKL; -.
DR OrthoDB; 1263520at2759; -.
DR PhylomeDB; Q8BLF1; -.
DR TreeFam; TF314978; -.
DR BRENDA; 3.1.1.13; 3474.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 320024; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Nceh1; mouse.
DR PRO; PR:Q8BLF1; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8BLF1; protein.
DR Bgee; ENSMUSG00000027698; Expressed in interventricular septum and 226 other tissues.
DR ExpressionAtlas; Q8BLF1; baseline and differential.
DR Genevisible; Q8BLF1; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047378; F:acetylalkylglycerol acetylhydrolase activity; IEA:RHEA.
DR GO; GO:0042301; F:phosphate ion binding; IDA:MGI.
DR GO; GO:0017171; F:serine hydrolase activity; IDA:MGI.
DR GO; GO:0046485; P:ether lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:MGI.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:MGI.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR017157; Arylacetamide_deacetylase.
DR InterPro; IPR033140; Lipase_GDXG_put_SER_AS.
DR Pfam; PF07859; Abhydrolase_3; 2.
DR PIRSF; PIRSF037251; Arylacetamide_deacetylase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS01174; LIPASE_GDXG_SER; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Lipid degradation; Lipid metabolism; Membrane; Microsome;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..408
FT /note="Neutral cholesterol ester hydrolase 1"
FT /id="PRO_0000265940"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..408
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT MOTIF 113..115
FT /note="Involved in the stabilization of the negatively
FT charged intermediate by the formation of the oxyanion hole"
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT ACT_SITE 191
FT /evidence="ECO:0000305|PubMed:16978018"
FT ACT_SITE 348
FT /evidence="ECO:0000305|PubMed:16978018"
FT ACT_SITE 378
FT /evidence="ECO:0000305|PubMed:16978018"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 93
FT /note="R -> Q (in Ref. 2; BAC28680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 408 AA; 45740 MW; FFEC0EA1CDCB59E7 CRC64;
MRSSCVLLAA LLALAAYYVY IPLPSAVSDP WKLMLLDATF RGAQQVSNLI HSLGLNHHLI
ALNFIITSFG KQSARSSPKV KVTDTDFDGV EVRVFEGSPK PEEPLRRSVI YIHGGGWALA
SAKISYYDQL CTTMAEELNA VIVSIEYRLV PQVYFPEQIH DVIRATKYFL QPEVLDKYKV
DPGRVGISGD SAGGNLAAAL GQQFTYVASL KNKLKLQALV YPVLQALDFN TPSYQQSMNT
PILPRHVMVR YWLDYFKGNY DFVEAMIVNN HTSLDVERAA ALRARLDWTS LLPSSIKKNY
KPIMQTTGNA RIVQEIPQLL DAAASPLIAE QEVLEALPKT YILTCEHDVL RDDGIMYAKR
LESAGVNVTL DHFEDGFHGC MIFTSWPTNF SVGIRTRNSY IKWLDQNL
