ERG1_HUMAN
ID ERG1_HUMAN Reviewed; 574 AA.
AC Q14534; Q9UEK6; Q9UNR6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Squalene monooxygenase;
DE EC=1.14.14.17 {ECO:0000269|PubMed:10666321, ECO:0000269|PubMed:30626872};
DE AltName: Full=Squalene epoxidase {ECO:0000303|PubMed:9286711};
DE Short=SE;
GN Name=SQLE; Synonyms=ERG1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9286711; DOI=10.1006/geno.1997.4825;
RA Nagai M., Sakakibara J., Wakui K., Fukushima Y., Igarashi S., Tsuji S.,
RA Arakawa M., Ono T.;
RT "Localization of the squalene epoxidase gene (SQLE) to human chromosome
RT region 8q24.1.";
RL Genomics 44:141-143(1997).
RN [2] {ECO:0000312|EMBL:AAD10823.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, COFACTOR, AND PATHWAY.
RC TISSUE=Liver {ECO:0000312|EMBL:AAD10823.1};
RX PubMed=10666321; DOI=10.1006/abbi.1999.1629;
RA Laden B.P., Tang Y., Porter T.D.;
RT "Cloning, heterologous expression, and enzymological characterization of
RT human squalene monooxygenase.";
RL Arch. Biochem. Biophys. 374:381-388(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary {ECO:0000312|EMBL:BAG36182.1};
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon {ECO:0000312|EMBL:AAH17033.1};
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 187-535.
RC TISSUE=Liver;
RX PubMed=8626488; DOI=10.1074/jbc.271.14.8053;
RA Nakamura Y., Sakakibara J., Izumi T., Shibata A., Ono T.;
RT "Transcriptional regulation of squalene epoxidase by sterols and inhibitors
RT in HeLa cells.";
RL J. Biol. Chem. 271:8053-8056(1996).
RN [9]
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., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP DOMAIN, INTERACTION WITH MARCHF6, UBIQUITINATION, AND PATHWAY.
RX PubMed=24449766; DOI=10.1128/mcb.01140-13;
RA Zelcer N., Sharpe L.J., Loregger A., Kristiana I., Cook E.C., Phan L.,
RA Stevenson J., Brown A.J.;
RT "The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects
RT 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol
RT synthesis pathway.";
RL Mol. Cell. Biol. 34:1262-1270(2014).
RN [11]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND DOMAIN.
RX PubMed=26434806; DOI=10.1074/jbc.m115.675181;
RA Howe V., Chua N.K., Stevenson J., Brown A.J.;
RT "The Regulatory Domain of Squalene Monooxygenase Contains a Re-entrant Loop
RT and Senses Cholesterol via a Conformational Change.";
RL J. Biol. Chem. 290:27533-27544(2015).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP DOMAIN, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF PHE-35; SER-37;
RP 62-GLN--LEU-73; LEU-65 AND ILE-69.
RX PubMed=28972164; DOI=10.1074/jbc.m117.794230;
RA Chua N.K., Howe V., Jatana N., Thukral L., Brown A.J.;
RT "A conserved degron containing an amphipathic helix regulates the
RT cholesterol-mediated turnover of human squalene monooxygenase, a rate-
RT limiting enzyme in cholesterol synthesis.";
RL J. Biol. Chem. 292:19959-19973(2017).
RN [14]
RP INTERACTION WITH SMIM22.
RX PubMed=29765154; DOI=10.1038/s41388-018-0281-5;
RA Polycarpou-Schwarz M., Gross M., Mestdagh P., Schott J., Grund S.E.,
RA Hildenbrand C., Rom J., Aulmann S., Sinn H.P., Vandesompele J.,
RA Diederichs S.;
RT "The cancer-associated microprotein CASIMO1 controls cell proliferation and
RT interacts with squalene epoxidase modulating lipid droplet formation.";
RL Oncogene 37:4750-4768(2018).
RN [15] {ECO:0007744|PDB:6C6N, ECO:0007744|PDB:6C6P, ECO:0007744|PDB:6C6R}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 118-574 IN COMPLEXES WITH FAD AND
RP SYNTHETIC INHIBITORS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, PATHWAY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP ACTIVITY REGULATION, MUTAGENESIS OF TYR-195, AND DOMAIN.
RX PubMed=30626872; DOI=10.1038/s41467-018-07928-x;
RA Padyana A.K., Gross S., Jin L., Cianchetta G., Narayanaswamy R., Wang F.,
RA Wang R., Fang C., Lv X., Biller S.A., Dang L., Mahoney C.E., Nagaraja N.,
RA Pirman D., Sui Z., Popovici-Muller J., Smolen G.A.;
RT "Structure and inhibition mechanism of the catalytic domain of human
RT squalene epoxidase.";
RL Nat. Commun. 10:97-97(2019).
CC -!- FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-
CC 2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in
CC steroid biosynthesis. {ECO:0000269|PubMed:10666321,
CC ECO:0000269|PubMed:30626872}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + squalene = (S)-
CC 2,3-epoxysqualene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:25282, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:15441, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.17;
CC Evidence={ECO:0000269|PubMed:10666321, ECO:0000269|PubMed:30626872};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:10666321, ECO:0000269|PubMed:30626872};
CC -!- ACTIVITY REGULATION: Inhibited by NB-598 ((E)N-ethyl-N-(6,6-dimethyl-2-
CC hepten-4-ynyl)-3-[(3,3'-bi-thiophen-5-yl)methoxy]benzene-methanamine).
CC Contrary to fungal enzymes, the mammalian enzyme is only slightly
CC inhibited by terbinafine (PubMed:30626872). Inhibited by tellurite,
CC tellurium dioxide, selenite, and selenium dioxide (PubMed:10666321).
CC {ECO:0000269|PubMed:10666321, ECO:0000269|PubMed:30626872}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.9 uM for squalene {ECO:0000269|PubMed:30626872};
CC KM=9.6 uM for FAD {ECO:0000269|PubMed:30626872};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 2/3. {ECO:0000269|PubMed:24449766,
CC ECO:0000305|PubMed:10666321, ECO:0000305|PubMed:30626872}.
CC -!- SUBUNIT: Interacts (via N-terminal domain) with MARCHF6. Interacts with
CC SMIM22; this interaction modulates lipid droplet formation
CC (PubMed:29765154). {ECO:0000269|PubMed:24449766,
CC ECO:0000269|PubMed:29765154}.
CC -!- INTERACTION:
CC Q14534; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-3905171, EBI-6942903;
CC Q14534; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-3905171, EBI-7545592;
CC Q14534; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-3905171, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:26434806,
CC ECO:0000269|PubMed:28972164, ECO:0000269|PubMed:30626872}; Peripheral
CC membrane protein {ECO:0000269|PubMed:26434806,
CC ECO:0000269|PubMed:28972164}. Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:26434806}; Peripheral membrane protein
CC {ECO:0000269|PubMed:26434806, ECO:0000269|PubMed:28972164}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level).
CC {ECO:0000269|PubMed:30626872}.
CC -!- DOMAIN: The C-terminal hydrophobic region contains two helices that
CC mediate interaction with membranes. Contrary to predictions, this
CC region does not contain transmembrane helices.
CC {ECO:0000269|PubMed:30626872}.
CC -!- DOMAIN: The N-terminal region mediates interaction with MARCHF6,
CC leading to SQLE ubiquitination and proteasomal degradation when
CC cholosterol levels are high (PubMed:24449766, PubMed:26434806,
CC PubMed:28972164). The first part of the N-terminal region contains a
CC hydrophobic region that inserts into the membrane; contrary to
CC predictions, there are no transmembrane helices (PubMed:26434806). The
CC second part contains a region that can form an amphipathic region that
CC associates with membranes. This region is ejected from the membrane by
CC high cholesterol levels and becomes disordered in an aqueous
CC environment. This is critical for cholesterol-dependent proteasomal
CC degradation. Additional parts of the N-terminal region are predicted to
CC be disordered and contribute to flagging the protein for proteasomal
CC degradation already under basal conditions (PubMed:28972164).
CC {ECO:0000269|PubMed:24449766, ECO:0000269|PubMed:26434806,
CC ECO:0000269|PubMed:28972164}.
CC -!- PTM: Ubiquitinated by MARCHF6 in response to high cholesterol levels in
CC intracellular membranes, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:24449766}.
CC -!- SIMILARITY: Belongs to the squalene monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; D78130; BAA22372.1; -; mRNA.
DR EMBL; AF098865; AAD10823.1; -; mRNA.
DR EMBL; AK313384; BAG36182.1; -; mRNA.
DR EMBL; BX647400; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC009908; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471060; EAW92079.1; -; Genomic_DNA.
DR EMBL; BC017033; AAH17033.1; -; mRNA.
DR EMBL; FJ695197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; D78129; BAA11209.1; -; mRNA.
DR CCDS; CCDS47918.1; -.
DR RefSeq; NP_003120.2; NM_003129.3.
DR PDB; 6C6N; X-ray; 2.30 A; A/B=118-574.
DR PDB; 6C6P; X-ray; 2.50 A; A/B=118-574.
DR PDB; 6C6R; X-ray; 3.00 A; A/B=118-574.
DR PDBsum; 6C6N; -.
DR PDBsum; 6C6P; -.
DR PDBsum; 6C6R; -.
DR AlphaFoldDB; Q14534; -.
DR SMR; Q14534; -.
DR BioGRID; 112591; 43.
DR IntAct; Q14534; 21.
DR MINT; Q14534; -.
DR STRING; 9606.ENSP00000265896; -.
DR BindingDB; Q14534; -.
DR ChEMBL; CHEMBL3592; -.
DR DrugBank; DB01091; Butenafine.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB00735; Naftifine.
DR DrugBank; DB00857; Terbinafine.
DR DrugCentral; Q14534; -.
DR GuidetoPHARMACOLOGY; 2433; -.
DR SwissLipids; SLP:000001243; -.
DR iPTMnet; Q14534; -.
DR PhosphoSitePlus; Q14534; -.
DR SwissPalm; Q14534; -.
DR BioMuta; SQLE; -.
DR DMDM; 296439362; -.
DR EPD; Q14534; -.
DR jPOST; Q14534; -.
DR MassIVE; Q14534; -.
DR PaxDb; Q14534; -.
DR PeptideAtlas; Q14534; -.
DR PRIDE; Q14534; -.
DR ProteomicsDB; 60034; -.
DR Antibodypedia; 27121; 166 antibodies from 27 providers.
DR DNASU; 6713; -.
DR Ensembl; ENST00000265896.10; ENSP00000265896.5; ENSG00000104549.12.
DR GeneID; 6713; -.
DR KEGG; hsa:6713; -.
DR MANE-Select; ENST00000265896.10; ENSP00000265896.5; NM_003129.4; NP_003120.2.
DR UCSC; uc011liq.3; human.
DR CTD; 6713; -.
DR DisGeNET; 6713; -.
DR GeneCards; SQLE; -.
DR HGNC; HGNC:11279; SQLE.
DR HPA; ENSG00000104549; Low tissue specificity.
DR MIM; 602019; gene.
DR neXtProt; NX_Q14534; -.
DR OpenTargets; ENSG00000104549; -.
DR PharmGKB; PA36108; -.
DR VEuPathDB; HostDB:ENSG00000104549; -.
DR eggNOG; KOG1298; Eukaryota.
DR GeneTree; ENSGT00390000011759; -.
DR InParanoid; Q14534; -.
DR OMA; KSKFWGL; -.
DR OrthoDB; 583514at2759; -.
DR PhylomeDB; Q14534; -.
DR TreeFam; TF331056; -.
DR BioCyc; MetaCyc:HS02595-MON; -.
DR BRENDA; 1.14.14.17; 2681.
DR PathwayCommons; Q14534; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR SABIO-RK; Q14534; -.
DR SignaLink; Q14534; -.
DR SIGNOR; Q14534; -.
DR UniPathway; UPA00767; UER00752.
DR BioGRID-ORCS; 6713; 53 hits in 1088 CRISPR screens.
DR ChiTaRS; SQLE; human.
DR GeneWiki; Squalene_monooxygenase; -.
DR GenomeRNAi; 6713; -.
DR Pharos; Q14534; Tchem.
DR PRO; PR:Q14534; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q14534; protein.
DR Bgee; ENSG00000104549; Expressed in adrenal tissue and 201 other tissues.
DR ExpressionAtlas; Q14534; baseline and differential.
DR Genevisible; Q14534; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0004506; F:squalene monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0006725; P:cellular aromatic compound metabolic process; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central.
DR GO; GO:0140042; P:lipid droplet formation; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR GO; GO:0016126; P:sterol biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR013698; Squalene_epoxidase.
DR InterPro; IPR040125; Squalene_monox.
DR PANTHER; PTHR10835; PTHR10835; 1.
DR Pfam; PF08491; SE; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; FAD; Flavoprotein; Lipid metabolism;
KW Membrane; Microsome; Oxidoreductase; Reference proteome; Ubl conjugation.
FT CHAIN 1..574
FT /note="Squalene monooxygenase"
FT /id="PRO_0000209838"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26434806"
FT INTRAMEM 21..41
FT /evidence="ECO:0000305|PubMed:26434806"
FT TOPO_DOM 42..574
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..100
FT /note="Interaction with MARCHF6"
FT /evidence="ECO:0000269|PubMed:24449766"
FT REGION 62..73
FT /note="Required for degradation in response to high
FT membrane cholesterol levels"
FT /evidence="ECO:0000269|PubMed:28972164"
FT REGION 118..574
FT /note="Sufficient for enzyme activity"
FT /evidence="ECO:0000269|PubMed:10666321,
FT ECO:0000269|PubMed:30626872"
FT REGION 516..574
FT /note="Hydrophobic; mediates interaction with membranes"
FT /evidence="ECO:0000269|PubMed:30626872"
FT BINDING 133..134
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 153..154
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 161
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 166
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 234
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 250
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 408
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT BINDING 421
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:30626872,
FT ECO:0007744|PDB:6C6N"
FT SITE 195
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000269|PubMed:30626872"
FT MUTAGEN 35
FT /note="F->A: Increased expression levels and decreased
FT degradation in response to high membrane cholesterol
FT levels; when associated with A-37; A-65 and A-69."
FT /evidence="ECO:0000269|PubMed:28972164"
FT MUTAGEN 37
FT /note="S->A: Increased expression levels and decreased
FT degradation in response to high membrane cholesterol
FT levels; when associated with A-35; A-65 and A-69."
FT /evidence="ECO:0000269|PubMed:28972164"
FT MUTAGEN 62..73
FT /note="Missing: Abolishes degradation in response to high
FT membrane cholesterol levels."
FT /evidence="ECO:0000269|PubMed:28972164"
FT MUTAGEN 65
FT /note="L->A: Increased expression levels and decreased
FT degradation in response to high membrane cholesterol
FT levels; when associated with A-35; A-37 and A-69."
FT /evidence="ECO:0000269|PubMed:28972164"
FT MUTAGEN 69
FT /note="I->A: Increased expression levels and decreased
FT degradation in response to high membrane cholesterol
FT levels; when associated with A-35; A-37 and A-65."
FT /evidence="ECO:0000269|PubMed:28972164"
FT MUTAGEN 195
FT /note="Y->A,F: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:30626872"
FT CONFLICT 43
FT /note="S -> F (in Ref. 3; BX647400)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="Q -> R (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="E -> G (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="A -> V (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="E -> G (in Ref. 8; BAA11209)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="I -> T (in Ref. 3; BX647400)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="Q -> R (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 379..380
FT /note="AT -> VA (in Ref. 3; BX647400)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="P -> L (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="K -> N (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="V -> A (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT CONFLICT 551
FT /note="G -> S (in Ref. 1; BAA22372)"
FT /evidence="ECO:0000305"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 133..144
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 169..177
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:6C6N"
FT TURN 200..203
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 243..267
FT /evidence="ECO:0007829|PDB:6C6N"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:6C6R"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 301..313
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 338..348
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 356..362
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 373..382
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 386..393
FT /evidence="ECO:0007829|PDB:6C6N"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 420..436
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 462..477
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 482..496
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 500..509
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 516..537
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 540..544
FT /evidence="ECO:0007829|PDB:6C6N"
FT HELIX 545..566
FT /evidence="ECO:0007829|PDB:6C6N"
SQ SEQUENCE 574 AA; 63923 MW; 6957F5CF1F1624C8 CRC64;
MWTFLGIATF TYFYKKFGDF ITLANREVLL CVLVFLSLGL VLSYRCRHRN GGLLGRQQSG
SQFALFSDIL SGLPFIGFFW AKSPPESENK EQLEARRRRK GTNISETSLI GTAACTSTSS
QNDPEVIIVG AGVLGSALAA VLSRDGRKVT VIERDLKEPD RIVGEFLQPG GYHVLKDLGL
GDTVEGLDAQ VVNGYMIHDQ ESKSEVQIPY PLSENNQVQS GRAFHHGRFI MSLRKAAMAE
PNAKFIEGVV LQLLEEDDVV MGVQYKDKET GDIKELHAPL TVVADGLFSK FRKSLVSNKV
SVSSHFVGFL MKNAPQFKAN HAELILANPS PVLIYQISSS ETRVLVDIRG EMPRNLREYM
VEKIYPQIPD HLKEPFLEAT DNSHLRSMPA SFLPPSSVKK RGVLLLGDAY NMRHPLTGGG
MTVAFKDIKL WRKLLKGIPD LYDDAAIFEA KKSFYWARKT SHSFVVNILA QALYELFSAT
DDSLHQLRKA CFLYFKLGGE CVAGPVGLLS VLSPNPLVLI GHFFAVAIYA VYFCFKSEPW
ITKPRALLSS GAVLYKACSV IFPLIYSEMK YMVH
