Full text data of NCEH1
NCEH1
(AADACL1, KIAA1363)
[Confidence: high (present in two of the MS resources)]
Neutral cholesterol ester hydrolase 1; NCEH; 3.1.1.- (Arylacetamide deacetylase-like 1)
Neutral cholesterol ester hydrolase 1; NCEH; 3.1.1.- (Arylacetamide deacetylase-like 1)
hRBCD
IPI00002230
IPI00002230 KIAA1363 protein KIAA1363 protein membrane n/a n/a n/a 3 3 n/a 3 n/a 2 n/a 1 n/a 2 1 1 1 1 1 n/a n/a membrane bound n/a found at its expected molecular weight found at molecular weight
IPI00002230 KIAA1363 protein KIAA1363 protein membrane n/a n/a n/a 3 3 n/a 3 n/a 2 n/a 1 n/a 2 1 1 1 1 1 n/a n/a membrane bound n/a found at its expected molecular weight found at molecular weight
Comments
Isoform Q6PIU2-2 was detected.
Isoform Q6PIU2-2 was detected.
UniProt
Q6PIU2
ID NCEH1_HUMAN Reviewed; 408 AA.
AC Q6PIU2; B7Z2K4; B7Z3A1; B7Z5U2; B7Z906; B7ZAW6; Q86WZ1; Q9P2I4;
read moreDT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 3.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Neutral cholesterol ester hydrolase 1;
DE Short=NCEH;
DE EC=3.1.1.-;
DE AltName: Full=Arylacetamide deacetylase-like 1;
GN Name=NCEH1; Synonyms=AADACL1, KIAA1363;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, Hippocampus, Testis, Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP MET-343.
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12149457; DOI=10.1073/pnas.162187599;
RA Jessani N., Liu Y., Humphrey M., Cravatt B.F.;
RT "Enzyme activity profiles of the secreted and membrane proteome that
RT depict cancer cell invasiveness.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10335-10340(2002).
RN [5]
RP FUNCTION.
RX PubMed=17052608; DOI=10.1016/j.chembiol.2006.08.008;
RA Chiang K.P., Niessen S., Saghatelian A., Cravatt B.F.;
RT "An enzyme that regulates ether lipid signaling pathways in cancer
RT annotated by multidimensional profiling.";
RL Chem. Biol. 13:1041-1050(2006).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-287, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Hydrolyzes 2-acetyl monoalkylglycerol ether, the
CC penultimate precursor of the pathway for de novo synthesis of
CC platelet-activating factor. May be responsible for cholesterol
CC ester hydrolysis in macrophages, thereby contributing to the
CC development of atherosclerosis. Also involved in organ
CC detoxification by hydrolyzing exogenous organophosphorus
CC compounds. May contribute to cancer pathogenesis by promoting
CC tumor cell migration.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane
CC protein (Probable). Microsome (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PIU2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PIU2-2; Sequence=VSP_037519;
CC Name=3;
CC IsoId=Q6PIU2-3; Sequence=VSP_037518;
CC -!- TISSUE SPECIFICITY: Expressed in monocyte-derived macrophages. Up-
CC regulated in invasive melanoma and breast carcinoma cell lines.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28734.2; Type=Erroneous initiation;
CC Sequence=AAH47588.2; Type=Erroneous initiation;
CC Sequence=BAA92601.1; Type=Erroneous initiation;
CC Sequence=BAH13028.1; Type=Erroneous initiation;
CC Sequence=BAH14142.1; Type=Erroneous initiation;
CC Sequence=BAH14802.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB037784; BAA92601.1; ALT_INIT; mRNA.
DR EMBL; AK294811; BAH11890.1; -; mRNA.
DR EMBL; AK295641; BAH12137.1; -; mRNA.
DR EMBL; AK299422; BAH13028.1; ALT_INIT; mRNA.
DR EMBL; AK304253; BAH14142.1; ALT_INIT; mRNA.
DR EMBL; AK316431; BAH14802.1; ALT_INIT; mRNA.
DR EMBL; BC028734; AAH28734.2; ALT_INIT; mRNA.
DR EMBL; BC047588; AAH47588.2; ALT_INIT; mRNA.
DR RefSeq; NP_001139748.1; NM_001146276.1.
DR RefSeq; NP_001139749.1; NM_001146277.1.
DR RefSeq; NP_001139750.1; NM_001146278.1.
DR RefSeq; NP_065843.3; NM_020792.4.
DR UniGene; Hs.444099; -.
DR ProteinModelPortal; Q6PIU2; -.
DR SMR; Q6PIU2; 90-385.
DR IntAct; Q6PIU2; 1.
DR STRING; 9606.ENSP00000273512; -.
DR BindingDB; Q6PIU2; -.
DR ChEMBL; CHEMBL5048; -.
DR MEROPS; S09.992; -.
DR PhosphoSite; Q6PIU2; -.
DR DMDM; 74737782; -.
DR PaxDb; Q6PIU2; -.
DR PRIDE; Q6PIU2; -.
DR DNASU; 57552; -.
DR Ensembl; ENST00000475381; ENSP00000418571; ENSG00000144959.
DR Ensembl; ENST00000543711; ENSP00000443227; ENSG00000144959.
DR GeneID; 57552; -.
DR KEGG; hsa:57552; -.
DR UCSC; uc011bpw.2; human.
DR CTD; 57552; -.
DR GeneCards; GC03M172348; -.
DR H-InvDB; HIX0003864; -.
DR H-InvDB; HIX0163448; -.
DR HGNC; HGNC:29260; NCEH1.
DR HPA; HPA026888; -.
DR MIM; 613234; gene.
DR neXtProt; NX_Q6PIU2; -.
DR PharmGKB; PA165697847; -.
DR eggNOG; COG0657; -.
DR HOVERGEN; HBG058974; -.
DR InParanoid; Q6PIU2; -.
DR KO; K14349; -.
DR OrthoDB; EOG7HB599; -.
DR ChiTaRS; NCEH1; human.
DR GeneWiki; NCEH1; -.
DR GenomeRNAi; 57552; -.
DR NextBio; 64018; -.
DR PRO; PR:Q6PIU2; -.
DR ArrayExpress; Q6PIU2; -.
DR Bgee; Q6PIU2; -.
DR CleanEx; HS_AADACL1; -.
DR Genevestigator; Q6PIU2; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR017157; Arylacetamide_deacetylase.
DR InterPro; IPR002168; Lipase_GDXG_AS.
DR Pfam; PF07859; Abhydrolase_3; 2.
DR PIRSF; PIRSF037251; Arylacetamide_deacetylase; 1.
DR PROSITE; PS01173; LIPASE_GDXG_HIS; FALSE_NEG.
DR PROSITE; PS01174; LIPASE_GDXG_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism;
KW Membrane; Microsome; Polymorphism; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 408 Neutral cholesterol ester hydrolase 1.
FT /FTId=PRO_0000265939.
FT TOPO_DOM 1 4 Cytoplasmic (Potential).
FT TRANSMEM 5 25 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 26 408 Lumenal (Potential).
FT MOTIF 113 115 Involved in the stabilization of the
FT negatively charged intermediate by the
FT formation of the oxyanion hole (By
FT similarity).
FT ACT_SITE 191 191 By similarity.
FT ACT_SITE 348 348 By similarity.
FT ACT_SITE 378 378 By similarity.
FT CARBOHYD 270 270 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 287 287 N-linked (GlcNAc...).
FT CARBOHYD 389 389 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 133 Missing (in isoform 3).
FT /FTId=VSP_037518.
FT VAR_SEQ 123 123 K -> SASWSPSDE (in isoform 2).
FT /FTId=VSP_037519.
FT VARIANT 19 19 V -> F (in dbSNP:rs35316420).
FT /FTId=VAR_047099.
FT VARIANT 71 71 K -> Q (in dbSNP:rs2302815).
FT /FTId=VAR_047100.
FT VARIANT 343 343 L -> M (in dbSNP:rs17857335).
FT /FTId=VAR_047101.
FT CONFLICT 16 16 A -> T (in Ref. 1; BAA92601).
FT CONFLICT 58 58 H -> R (in Ref. 2; BAH13028).
FT CONFLICT 72 72 K -> R (in Ref. 2; BAH14802).
FT CONFLICT 79 79 Q -> K (in Ref. 3; AAH47588).
FT CONFLICT 254 254 D -> G (in Ref. 2; BAH14142).
FT CONFLICT 329 329 A -> S (in Ref. 2; BAH14142).
SQ SEQUENCE 408 AA; 45808 MW; E5754850BE9805B5 CRC64;
MRSSCVLLTA LVALAAYYVY IPLPGSVSDP WKLMLLDATF RGAQQVSNLI HYLGLSHHLL
ALNFIIVSFG KKSAWSSAQV KVTDTDFDGV EVRVFEGPPK PEEPLKRSVV YIHGGGWALA
SAKIRYYDEL CTAMAEELNA VIVSIEYRLV PKVYFPEQIH DVVRATKYFL KPEVLQKYMV
DPGRICISGD SAGGNLAAAL GQQFTQDASL KNKLKLQALI YPVLQALDFN TPSYQQNVNT
PILPRYVMVK YWVDYFKGNY DFVQAMIVNN HTSLDVEEAA AVRARLNWTS LLPASFTKNY
KPVVQTTGNA RIVQELPQLL DARSAPLIAD QAVLQLLPKT YILTCEHDVL RDDGIMYAKR
LESAGVEVTL DHFEDGFHGC MIFTSWPTNF SVGIRTRNSY IKWLDQNL
//
ID NCEH1_HUMAN Reviewed; 408 AA.
AC Q6PIU2; B7Z2K4; B7Z3A1; B7Z5U2; B7Z906; B7ZAW6; Q86WZ1; Q9P2I4;
read moreDT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 3.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Neutral cholesterol ester hydrolase 1;
DE Short=NCEH;
DE EC=3.1.1.-;
DE AltName: Full=Arylacetamide deacetylase-like 1;
GN Name=NCEH1; Synonyms=AADACL1, KIAA1363;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, Hippocampus, Testis, Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP MET-343.
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12149457; DOI=10.1073/pnas.162187599;
RA Jessani N., Liu Y., Humphrey M., Cravatt B.F.;
RT "Enzyme activity profiles of the secreted and membrane proteome that
RT depict cancer cell invasiveness.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10335-10340(2002).
RN [5]
RP FUNCTION.
RX PubMed=17052608; DOI=10.1016/j.chembiol.2006.08.008;
RA Chiang K.P., Niessen S., Saghatelian A., Cravatt B.F.;
RT "An enzyme that regulates ether lipid signaling pathways in cancer
RT annotated by multidimensional profiling.";
RL Chem. Biol. 13:1041-1050(2006).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-287, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Hydrolyzes 2-acetyl monoalkylglycerol ether, the
CC penultimate precursor of the pathway for de novo synthesis of
CC platelet-activating factor. May be responsible for cholesterol
CC ester hydrolysis in macrophages, thereby contributing to the
CC development of atherosclerosis. Also involved in organ
CC detoxification by hydrolyzing exogenous organophosphorus
CC compounds. May contribute to cancer pathogenesis by promoting
CC tumor cell migration.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane
CC protein (Probable). Microsome (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PIU2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PIU2-2; Sequence=VSP_037519;
CC Name=3;
CC IsoId=Q6PIU2-3; Sequence=VSP_037518;
CC -!- TISSUE SPECIFICITY: Expressed in monocyte-derived macrophages. Up-
CC regulated in invasive melanoma and breast carcinoma cell lines.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28734.2; Type=Erroneous initiation;
CC Sequence=AAH47588.2; Type=Erroneous initiation;
CC Sequence=BAA92601.1; Type=Erroneous initiation;
CC Sequence=BAH13028.1; Type=Erroneous initiation;
CC Sequence=BAH14142.1; Type=Erroneous initiation;
CC Sequence=BAH14802.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB037784; BAA92601.1; ALT_INIT; mRNA.
DR EMBL; AK294811; BAH11890.1; -; mRNA.
DR EMBL; AK295641; BAH12137.1; -; mRNA.
DR EMBL; AK299422; BAH13028.1; ALT_INIT; mRNA.
DR EMBL; AK304253; BAH14142.1; ALT_INIT; mRNA.
DR EMBL; AK316431; BAH14802.1; ALT_INIT; mRNA.
DR EMBL; BC028734; AAH28734.2; ALT_INIT; mRNA.
DR EMBL; BC047588; AAH47588.2; ALT_INIT; mRNA.
DR RefSeq; NP_001139748.1; NM_001146276.1.
DR RefSeq; NP_001139749.1; NM_001146277.1.
DR RefSeq; NP_001139750.1; NM_001146278.1.
DR RefSeq; NP_065843.3; NM_020792.4.
DR UniGene; Hs.444099; -.
DR ProteinModelPortal; Q6PIU2; -.
DR SMR; Q6PIU2; 90-385.
DR IntAct; Q6PIU2; 1.
DR STRING; 9606.ENSP00000273512; -.
DR BindingDB; Q6PIU2; -.
DR ChEMBL; CHEMBL5048; -.
DR MEROPS; S09.992; -.
DR PhosphoSite; Q6PIU2; -.
DR DMDM; 74737782; -.
DR PaxDb; Q6PIU2; -.
DR PRIDE; Q6PIU2; -.
DR DNASU; 57552; -.
DR Ensembl; ENST00000475381; ENSP00000418571; ENSG00000144959.
DR Ensembl; ENST00000543711; ENSP00000443227; ENSG00000144959.
DR GeneID; 57552; -.
DR KEGG; hsa:57552; -.
DR UCSC; uc011bpw.2; human.
DR CTD; 57552; -.
DR GeneCards; GC03M172348; -.
DR H-InvDB; HIX0003864; -.
DR H-InvDB; HIX0163448; -.
DR HGNC; HGNC:29260; NCEH1.
DR HPA; HPA026888; -.
DR MIM; 613234; gene.
DR neXtProt; NX_Q6PIU2; -.
DR PharmGKB; PA165697847; -.
DR eggNOG; COG0657; -.
DR HOVERGEN; HBG058974; -.
DR InParanoid; Q6PIU2; -.
DR KO; K14349; -.
DR OrthoDB; EOG7HB599; -.
DR ChiTaRS; NCEH1; human.
DR GeneWiki; NCEH1; -.
DR GenomeRNAi; 57552; -.
DR NextBio; 64018; -.
DR PRO; PR:Q6PIU2; -.
DR ArrayExpress; Q6PIU2; -.
DR Bgee; Q6PIU2; -.
DR CleanEx; HS_AADACL1; -.
DR Genevestigator; Q6PIU2; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR017157; Arylacetamide_deacetylase.
DR InterPro; IPR002168; Lipase_GDXG_AS.
DR Pfam; PF07859; Abhydrolase_3; 2.
DR PIRSF; PIRSF037251; Arylacetamide_deacetylase; 1.
DR PROSITE; PS01173; LIPASE_GDXG_HIS; FALSE_NEG.
DR PROSITE; PS01174; LIPASE_GDXG_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism;
KW Membrane; Microsome; Polymorphism; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 408 Neutral cholesterol ester hydrolase 1.
FT /FTId=PRO_0000265939.
FT TOPO_DOM 1 4 Cytoplasmic (Potential).
FT TRANSMEM 5 25 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 26 408 Lumenal (Potential).
FT MOTIF 113 115 Involved in the stabilization of the
FT negatively charged intermediate by the
FT formation of the oxyanion hole (By
FT similarity).
FT ACT_SITE 191 191 By similarity.
FT ACT_SITE 348 348 By similarity.
FT ACT_SITE 378 378 By similarity.
FT CARBOHYD 270 270 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 287 287 N-linked (GlcNAc...).
FT CARBOHYD 389 389 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 133 Missing (in isoform 3).
FT /FTId=VSP_037518.
FT VAR_SEQ 123 123 K -> SASWSPSDE (in isoform 2).
FT /FTId=VSP_037519.
FT VARIANT 19 19 V -> F (in dbSNP:rs35316420).
FT /FTId=VAR_047099.
FT VARIANT 71 71 K -> Q (in dbSNP:rs2302815).
FT /FTId=VAR_047100.
FT VARIANT 343 343 L -> M (in dbSNP:rs17857335).
FT /FTId=VAR_047101.
FT CONFLICT 16 16 A -> T (in Ref. 1; BAA92601).
FT CONFLICT 58 58 H -> R (in Ref. 2; BAH13028).
FT CONFLICT 72 72 K -> R (in Ref. 2; BAH14802).
FT CONFLICT 79 79 Q -> K (in Ref. 3; AAH47588).
FT CONFLICT 254 254 D -> G (in Ref. 2; BAH14142).
FT CONFLICT 329 329 A -> S (in Ref. 2; BAH14142).
SQ SEQUENCE 408 AA; 45808 MW; E5754850BE9805B5 CRC64;
MRSSCVLLTA LVALAAYYVY IPLPGSVSDP WKLMLLDATF RGAQQVSNLI HYLGLSHHLL
ALNFIIVSFG KKSAWSSAQV KVTDTDFDGV EVRVFEGPPK PEEPLKRSVV YIHGGGWALA
SAKIRYYDEL CTAMAEELNA VIVSIEYRLV PKVYFPEQIH DVVRATKYFL KPEVLQKYMV
DPGRICISGD SAGGNLAAAL GQQFTQDASL KNKLKLQALI YPVLQALDFN TPSYQQNVNT
PILPRYVMVK YWVDYFKGNY DFVQAMIVNN HTSLDVEEAA AVRARLNWTS LLPASFTKNY
KPVVQTTGNA RIVQELPQLL DARSAPLIAD QAVLQLLPKT YILTCEHDVL RDDGIMYAKR
LESAGVEVTL DHFEDGFHGC MIFTSWPTNF SVGIRTRNSY IKWLDQNL
//
MIM
613234
*RECORD*
*FIELD* NO
613234
*FIELD* TI
*613234 NEUTRAL CHOLESTEROL ESTER HYDROLASE 1; NCEH1
;;NCEH;;
KIAA1363
*FIELD* TX
read moreCLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) cloned NCEH1, which they designated
KIAA1363. The deduced 430-amino acid protein shares significant
similarity with rabbit hepatic esterase/N-deacetylase. RT-PCR ELISA
detected highest NCEH1 expression in adult amygdala, followed by whole
adult and fetal brain and most adult brain regions examined. Strong
expression was also detected in adult kidney, heart, liver, skeletal
muscle, and ovary and in fetal liver. Weaker expression was detected in
all other adult tissues examined.
Okazaki et al. (2008) cloned mouse Nceh. The deduced 408-amino acid
protein contains an N-terminal transmembrane domain, a central catalytic
core domain, and a C-terminal lipid-binding domain. Mouse and human HCEH
share 87.5% amino acid identity. Northern blot analysis revealed high
Nceh expression in mouse peritoneal macrophages and kidney, with weaker
expression in heart and adrenal tissue, and none in other tissues
examined. NCEH expression was low in freshly isolated human monocytes,
but it was induced during differentiation to mature macrophages.
GENE FUNCTION
Using integrated enzyme and small molecule profiling, Chiang et al.
(2006) identified KIAA1363 as a 2-acetyl monoalkylglycerol ether
hydrolase with a key regulatory role in an ether lipid signaling
network. Pharmacologic inhibition of KIAA1363 in the SKOV-3 invasive
ovarian cancer cell line dramatically reduced the levels of a specific
set of lipophilic metabolites associated with aggressive cancers.
Downregulation of KIAA1363 expression via short hairpin RNA resulted in
a similar reduction in these metabolites, and it reduced the
tumorigenicity of SKOV-3 cells following injection in immune-deficient
mice. In vitro studies showed that the decreased tumorigenic potential
of KIAA1363-knockdown SKOV-3 cells was due to reduced migration capacity
rather than reduced cell proliferation.
Unstable lipid-rich plaques in atherosclerosis are characterized by the
accumulation of macrophage foam cells loaded with cholesterol ester
(CE), which is reduced by CE hydrolases. Okazaki et al. (2008) found
that membrane-bound Nceh accounted for a major part of the CE hydrolase
activity in mouse peritoneal macrophages. Nceh showed a pH optimum of
7.2 with CE as substrate, and it also showed significant triacylglycerol
hydrolase activity. RNA interference experiments showed that at least
half of the CE hydrolase activity of mouse peritoneal macrophages was
mediated by Nceh, and overexpression of Nceh was associated with
decreased intracellular CE content. Immunohistochemical analysis
revealed prominent expression of Nceh in macrophages surrounding
atherosclerotic lesions in Apoe (107741) -/- mice.
Nomura et al. (2010) found that KIAA1363 and MAGL (MGLL; 609699) were
consistently elevated in aggressive human cancer cells relative to their
nonaggressive counterparts. The authors suggested that enrichment of
protumorigenic lipid signaling molecules in aggressive cancer cells
supports their malignant phenotype.
MAPPING
Hartz (2010) mapped the NCEH1 gene to chromosome 3q26.31 based on an
alignment of the NCEH1 sequence (GenBank GENBANK AB037784) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Chiang, K. P.; Niessen, S.; Saghatelian, A.; Cravatt, B. F.: An
enzyme that regulates ether lipid signaling pathways in cancer annotated
by multidimensional profiling. Chem. Biol. 13: 1041-1050, 2006.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/27/2010.
3. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
4. Nomura, D. K.; Long, J. Z.; Niessen, S.; Hoover, H. S.; Ng, S.-W.;
Cravatt, B. F.: Monoacylglycerol lipase regulates a fatty acid network
that promotes cancer pathogenesis. Cell 140: 49-61, 2010.
5. Okazaki, H.; Igarashi, M.; Nishi, M.; Sekiya, M.; Tajima, M.; Takase,
S.; Takanashi, M.; Ohta, K.; Tamura, Y.; Okazaki, S.; Yahagi, N.;
Ohashi, K.; Amemiya-Kudo, M.; Nakagawa, Y.; Nagai, R.; Kadowaki, T.;
Osuga, J.; Ishibashi, S.: Identification of neutral cholesterol ester
hydrolase, a key enzyme removing cholesterol from macrophages. J.
Biol. Chem. 283: 33357-33364, 2008.
*FIELD* CD
Patricia A. Hartz: 1/27/2010
*FIELD* ED
terry: 11/16/2010
mgross: 1/27/2010
*RECORD*
*FIELD* NO
613234
*FIELD* TI
*613234 NEUTRAL CHOLESTEROL ESTER HYDROLASE 1; NCEH1
;;NCEH;;
KIAA1363
*FIELD* TX
read moreCLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) cloned NCEH1, which they designated
KIAA1363. The deduced 430-amino acid protein shares significant
similarity with rabbit hepatic esterase/N-deacetylase. RT-PCR ELISA
detected highest NCEH1 expression in adult amygdala, followed by whole
adult and fetal brain and most adult brain regions examined. Strong
expression was also detected in adult kidney, heart, liver, skeletal
muscle, and ovary and in fetal liver. Weaker expression was detected in
all other adult tissues examined.
Okazaki et al. (2008) cloned mouse Nceh. The deduced 408-amino acid
protein contains an N-terminal transmembrane domain, a central catalytic
core domain, and a C-terminal lipid-binding domain. Mouse and human HCEH
share 87.5% amino acid identity. Northern blot analysis revealed high
Nceh expression in mouse peritoneal macrophages and kidney, with weaker
expression in heart and adrenal tissue, and none in other tissues
examined. NCEH expression was low in freshly isolated human monocytes,
but it was induced during differentiation to mature macrophages.
GENE FUNCTION
Using integrated enzyme and small molecule profiling, Chiang et al.
(2006) identified KIAA1363 as a 2-acetyl monoalkylglycerol ether
hydrolase with a key regulatory role in an ether lipid signaling
network. Pharmacologic inhibition of KIAA1363 in the SKOV-3 invasive
ovarian cancer cell line dramatically reduced the levels of a specific
set of lipophilic metabolites associated with aggressive cancers.
Downregulation of KIAA1363 expression via short hairpin RNA resulted in
a similar reduction in these metabolites, and it reduced the
tumorigenicity of SKOV-3 cells following injection in immune-deficient
mice. In vitro studies showed that the decreased tumorigenic potential
of KIAA1363-knockdown SKOV-3 cells was due to reduced migration capacity
rather than reduced cell proliferation.
Unstable lipid-rich plaques in atherosclerosis are characterized by the
accumulation of macrophage foam cells loaded with cholesterol ester
(CE), which is reduced by CE hydrolases. Okazaki et al. (2008) found
that membrane-bound Nceh accounted for a major part of the CE hydrolase
activity in mouse peritoneal macrophages. Nceh showed a pH optimum of
7.2 with CE as substrate, and it also showed significant triacylglycerol
hydrolase activity. RNA interference experiments showed that at least
half of the CE hydrolase activity of mouse peritoneal macrophages was
mediated by Nceh, and overexpression of Nceh was associated with
decreased intracellular CE content. Immunohistochemical analysis
revealed prominent expression of Nceh in macrophages surrounding
atherosclerotic lesions in Apoe (107741) -/- mice.
Nomura et al. (2010) found that KIAA1363 and MAGL (MGLL; 609699) were
consistently elevated in aggressive human cancer cells relative to their
nonaggressive counterparts. The authors suggested that enrichment of
protumorigenic lipid signaling molecules in aggressive cancer cells
supports their malignant phenotype.
MAPPING
Hartz (2010) mapped the NCEH1 gene to chromosome 3q26.31 based on an
alignment of the NCEH1 sequence (GenBank GENBANK AB037784) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Chiang, K. P.; Niessen, S.; Saghatelian, A.; Cravatt, B. F.: An
enzyme that regulates ether lipid signaling pathways in cancer annotated
by multidimensional profiling. Chem. Biol. 13: 1041-1050, 2006.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/27/2010.
3. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
4. Nomura, D. K.; Long, J. Z.; Niessen, S.; Hoover, H. S.; Ng, S.-W.;
Cravatt, B. F.: Monoacylglycerol lipase regulates a fatty acid network
that promotes cancer pathogenesis. Cell 140: 49-61, 2010.
5. Okazaki, H.; Igarashi, M.; Nishi, M.; Sekiya, M.; Tajima, M.; Takase,
S.; Takanashi, M.; Ohta, K.; Tamura, Y.; Okazaki, S.; Yahagi, N.;
Ohashi, K.; Amemiya-Kudo, M.; Nakagawa, Y.; Nagai, R.; Kadowaki, T.;
Osuga, J.; Ishibashi, S.: Identification of neutral cholesterol ester
hydrolase, a key enzyme removing cholesterol from macrophages. J.
Biol. Chem. 283: 33357-33364, 2008.
*FIELD* CD
Patricia A. Hartz: 1/27/2010
*FIELD* ED
terry: 11/16/2010
mgross: 1/27/2010