ID LSS_HUMAN Reviewed; 732 AA. AC P48449; B4DJZ9; D3DSN0; E9PEI9; G5E9Q9; Q8IYL6; Q9UEZ1; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 02-SEP-2026, entry version 220. DE RecName: Full=Lanosterol synthase; DE EC=5.4.99.7 {ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:26200341, ECO:0000269|PubMed:7639730}; DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase; DE AltName: Full=Oxidosqualene--lanosterol cyclase; DE Short=OSC; DE Short=hOSC; GN Name=LSS; Synonyms=OSC; 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] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=7639730; DOI=10.1006/bbrc.1995.2110; RA Baker C.H., Matsuda S.P.T., Liu D.R., Corey E.J.; RT "Molecular cloning of the human gene encoding lanosterol synthase from a RT liver cDNA library."; RL Biochem. Biophys. Res. Commun. 213:154-160(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal liver; RX PubMed=8593458; DOI=10.1248/bpb.18.1459; RA Sung C.K., Shibuya M., Sankawa U., Ebizuka Y.; RT "Molecular cloning of cDNA encoding human lanosterol synthase."; RL Biol. Pharm. Bull. 18:1459-1461(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT VAL-642. RC TISSUE=Thalamus; 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 [GENOMIC DNA]. RX PubMed=10598817; DOI=10.1007/s004390051135; RA Roessler E., Mittaz L., Du Y., Scott H.S., Chang J., Rossier C., RA Guipponi M., Matsuda S.P., Muenke M., Antonarakis S.E.; RT "Structure of the human lanosterol synthase gene and its analysis as a RT candidate for holoprosencephaly."; RL Hum. Genet. 105:489-495(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-642. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-642. RC 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 [9] RP PROTEIN SEQUENCE OF 2-5, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, RP AND FUNCTION. RX PubMed=14766201; DOI=10.1016/j.bbrc.2004.01.052; RA Ruf A., Muller F., D'Arcy B., Stihle M., Kusznir E., Handschin C., RA Morand O.H., Thoma R.; RT "The monotopic membrane protein human oxidosqualene cyclase is active as RT monomer."; RL Biochem. Biophys. Res. Commun. 315:247-254(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 41-630 (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=8655142; DOI=10.1007/bf02281872; RA Young M., Chen H., Lalioti M.D., Antonarakis S.E.; RT "The human lanosterol synthase gene maps to chromosome 21q22.3."; RL Hum. Genet. 97:620-624(1996). RN [11] 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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP FUNCTION, INVOLVEMENT IN CTRCT44, VARIANTS CTRCT44 ARG-581 AND SER-588, RP CHARACTERIZATION OF VARIANTS CTRCT44 ARG-581 AND SER-588, AND CATALYTIC RP ACTIVITY. RX PubMed=26200341; DOI=10.1038/nature14650; RA Zhao L., Chen X.J., Zhu J., Xi Y.B., Yang X., Hu L.D., Ouyang H., RA Patel S.H., Jin X., Lin D., Wu F., Flagg K., Cai H., Li G., Cao G., Lin Y., RA Chen D., Wen C., Chung C., Wang Y., Qiu A., Yeh E., Wang W., Hu X., RA Grob S., Abagyan R., Su Z., Tjondro H.C., Zhao X.J., Luo H., Hou R., RA Perry J.J., Gao W., Kozak I., Granet D., Li Y., Sun X., Wang J., Zhang L., RA Liu Y., Yan Y.B., Zhang K.; RT "Lanosterol reverses protein aggregation in cataracts."; RL Nature 523:607-611(2015). RN [15] 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 [16] RP VARIANTS CTRCT44 SER-342 AND CYS-629. RX PubMed=29016354; DOI=10.1515/jpem-2017-0101; RA Chen X., Liu L.; RT "Congenital cataract with LSS gene mutations: a new case report."; RL J. Pediatr. Endocrinol. Metab. 30:1231-1235(2017). RN [17] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN HYPT14, RP INVOLVEMENT IN APMR4, VARIANTS HYPT14 VAL-102; PRO-248 AND SER-391, RP VARIANTS APMR4 141-TRP--PRO-732 DEL AND TYR-209, CHARACTERIZATION OF RP VARIANTS HYPT14 VAL-102; PRO-248 AND SER-391, AND CHARACTERIZATION OF RP VARIANTS APMR4 141-TRP--PRO-732 DEL AND TYR-209. RX PubMed=30401459; DOI=10.1016/j.ajhg.2018.09.011; RA Romano M.T., Tafazzoli A., Mattern M., Sivalingam S., Wolf S., Rupp A., RA Thiele H., Altmueller J., Nuernberg P., Ellwanger J., Gambon R., Baumer A., RA Kohlschmidt N., Metze D., Holdenrieder S., Paus R., Luetjohann D., RA Frank J., Geyer M., Bertolini M., Kokordelis P., Betz R.C.; RT "Bi-allelic mutations in LSS, encoding lanosterol synthase, cause RT autosomal-recessive hypotrichosis simplex."; RL Am. J. Hum. Genet. 103:777-785(2018). RN [18] RP INVOLVEMENT IN APMR4, AND VARIANTS APMR4 ASP-12; CYS-14; PRO-260; CYS-286; RP SER-516; 604-ARG--PRO-732 DEL; ILE-652 AND LYS-705. RX PubMed=30723320; DOI=10.1038/s41436-019-0445-x; RA Besnard T., Sloboda N., Goldenberg A., Kuery S., Cogne B., Breheret F., RA Trochu E., Conrad S., Vincent M., Deb W., Balguerie X., Barbarot S., RA Baujat G., Ben-Omran T., Bursztejn A.C., Carmignac V., Datta A.N., RA Delignieres A., Faivre L., Gardie B., Gueant J.L., Kuentz P., Lenglet M., RA Nassogne M.C., Ramaekers V., Schnur R.E., Si Y., Torti E., Thevenon J., RA Vabres P., Van Maldergem L., Wand D., Wiedemann A., Cariou B., Redon R., RA Lamaziere A., Bezieau S., Feillet F., Isidor B.; RT "Biallelic pathogenic variants in the lanosterol synthase gene LSS involved RT in the cholesterol biosynthesis cause alopecia with intellectual RT disability, a rare recessive neuroectodermal syndrome."; RL Genet. Med. 21:2025-2035(2019). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH LANOSTEROL AND RO RP 48-807, SUBCELLULAR LOCATION, AND ACTIVE SITE. RX PubMed=15525992; DOI=10.1038/nature02993; RA Thoma R., Schulz-Gasch T., D'Arcy B., Benz J., Aebi J., Dehmlow H., RA Hennig M., Stihle M., Ruf A.; RT "Insight into steroid scaffold formation from the structure of human RT oxidosqualene cyclase."; RL Nature 432:118-122(2004). CC -!- FUNCTION: Key enzyme in the cholesterol biosynthesis pathway. Catalyzes CC the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that CC forms the sterol nucleus (PubMed:14766201, PubMed:26200341, CC PubMed:7639730). Through the production of lanosterol may regulate lens CC protein aggregation and increase transparency (PubMed:26200341). CC {ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:26200341, CC ECO:0000269|PubMed:7639730}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-2,3-epoxysqualene = lanosterol; Xref=Rhea:RHEA:14621, CC ChEBI:CHEBI:15441, ChEBI:CHEBI:16521; EC=5.4.99.7; CC Evidence={ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:26200341, CC ECO:0000269|PubMed:7639730}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622; CC Evidence={ECO:0000305|PubMed:14766201}; CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from CC farnesyl diphosphate: step 3/3. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:14766201}. CC -!- INTERACTION: CC P48449; Q13520: AQP6; NbExp=3; IntAct=EBI-3930711, EBI-13059134; CC P48449; Q99828: CIB1; NbExp=3; IntAct=EBI-3930711, EBI-372594; CC P48449; Q14973: SLC10A1; NbExp=3; IntAct=EBI-3930711, EBI-3923031; CC P48449; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-3930711, EBI-18159983; CC P48449; Q9NRX6: TMEM167B; NbExp=3; IntAct=EBI-3930711, EBI-17684533; CC P48449; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-3930711, EBI-2548832; CC P48449; O95070: YIF1A; NbExp=3; IntAct=EBI-3930711, EBI-2799703; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:15525992, CC ECO:0000269|PubMed:30401459}; Peripheral membrane protein CC {ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:15525992}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P48449-1; Sequence=Displayed; CC Name=2; CC IsoId=P48449-2; Sequence=VSP_045407; CC Name=3; CC IsoId=P48449-3; Sequence=VSP_046188; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in the hair bulb, the CC outer root sheath and hair matrix of the hair follicle epithelium. Also CC detected in dermal papilla, epidermis, sweat glands, sebaceous glands, CC and blood vessels. {ECO:0000269|PubMed:30401459}. CC -!- DISEASE: Cataract 44 (CTRCT44) [MIM:616509]: An opacification of the CC crystalline lens of the eye that frequently results in visual CC impairment or blindness. Opacities vary in morphology, are often CC confined to a portion of the lens, and may be static or progressive. In CC general, the more posteriorly located and dense an opacity, the greater CC the impact on visual function. {ECO:0000269|PubMed:26200341, CC ECO:0000269|PubMed:29016354}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hypotrichosis 14 (HYPT14) [MIM:618275]: A form of CC hypotrichosis, a condition characterized by the presence of less than CC the normal amount of hair and abnormal hair follicles and shafts, which CC are thin and atrophic. The extent of scalp and body hair involvement CC can be very variable, within as well as between families. HYPT14 is an CC autosomal recessive form characterized by sparse to absent lanugo-like CC scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body CC hair. {ECO:0000269|PubMed:30401459}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Alopecia-intellectual disability syndrome 4 (APMR4) CC [MIM:618840]: An autosomal recessive disorder characterized by alopecia CC universalis, scaly skin, mild to severe intellectual disability, CC delayed or absent speech, and motor delay. CC {ECO:0000269|PubMed:30401459, ECO:0000269|PubMed:30723320}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the terpene cyclase/mutase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U22526; AAC50184.1; -; mRNA. DR EMBL; D63807; BAA09875.1; -; mRNA. DR EMBL; S81221; AAB36220.1; -; mRNA. DR EMBL; AJ239031; CAB42828.1; -; Genomic_DNA. DR EMBL; AJ239021; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239022; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239023; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239024; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239025; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239026; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239027; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239028; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239029; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AJ239030; CAB42828.1; JOINED; Genomic_DNA. DR EMBL; AK296313; BAG59011.1; -; mRNA. DR EMBL; AK226141; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AP001468; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001469; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471079; EAX09299.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09301.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09302.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09303.1; -; Genomic_DNA. DR EMBL; BC035638; AAH35638.1; -; mRNA. DR EMBL; X87809; CAA61078.1; -; mRNA. DR CCDS; CCDS13733.1; -. [P48449-1] DR CCDS; CCDS46654.1; -. [P48449-3] DR CCDS; CCDS54489.1; -. [P48449-2] DR PIR; JC4194; JC4194. DR RefSeq; NP_001001438.1; NM_001001438.3. [P48449-1] DR RefSeq; NP_001138908.1; NM_001145436.2. [P48449-3] DR RefSeq; NP_001138909.1; NM_001145437.2. [P48449-2] DR RefSeq; NP_002331.3; NM_002340.6. [P48449-1] DR PDB; 1W6J; X-ray; 2.20 A; A=1-732. DR PDB; 1W6K; X-ray; 2.10 A; A=1-732. DR AlphaFoldDB; P48449; -. DR MDRepo; P48449; -. DR SMR; P48449; -. DR BioGRID; 110225; 84. DR FunCoup; P48449; 530. DR IntAct; P48449; 57. DR MINT; P48449; -. DR NDEx; IQUERY-CP-LSS; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000380837; -. DR BindingDB; P48449; -. DR ChEMBL; CHEMBL3593; -. DR DrugBank; DB03696; Lanosterol. DR DrugBank; DB02016; R048-8071. DR GuidetoPHARMACOLOGY; 2434; -. DR SwissLipids; SLP:000001308; -. [P48449-1] DR GlyGen; P48449; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P48449; -. DR PhosphoSitePlus; P48449; -. DR SwissPalm; P48449; -. DR BioMuta; LSS; -. DR DMDM; 1352387; -. DR jPOST; P48449; -. DR MassIVE; P48449; -. DR PaxDb; 9606-ENSP00000380837; -. DR PeptideAtlas; P48449; -. DR ProteomicsDB; 19902; -. DR ProteomicsDB; 34015; -. DR ProteomicsDB; 55893; -. [P48449-1] DR Pumba; P48449; -. DR Antibodypedia; 24599; 164 antibodies from 29 providers. DR DNASU; 4047; -. DR Ensembl; ENST00000356396.8; ENSP00000348762.3; ENSG00000160285.16. [P48449-1] DR Ensembl; ENST00000397728.8; ENSP00000380837.2; ENSG00000160285.16. [P48449-1] DR Ensembl; ENST00000457828.6; ENSP00000409191.2; ENSG00000160285.16. [P48449-2] DR Ensembl; ENST00000522411.5; ENSP00000429133.1; ENSG00000160285.16. [P48449-3] DR GeneID; 4047; -. DR KEGG; hsa:4047; -. DR MANE-Select; ENST00000397728.8; ENSP00000380837.2; NM_002340.6; NP_002331.3. DR UCSC; uc002zij.4; human. [P48449-1] DR AGR; HGNC:6708; -. DR ClinPGx; PA30473; -. DR CTD; 4047; -. DR DisGeNET; 4047; -. DR GeneCards; LSS; -. DR HGNC; HGNC:6708; LSS. DR HPA; ENSG00000160285; Low tissue specificity. DR MalaCards; LSS; -. DR MIM; 600909; gene. DR MIM; 616509; phenotype. DR MIM; 618275; phenotype. DR MIM; 618840; phenotype. DR OpenTargets; ENSG00000160285; -. DR Orphanet; 2850; Alopecia-intellectual disability syndrome. DR Orphanet; 1366; Autosomal recessive palmoplantar keratoderma and congenital alopecia. DR Orphanet; 55654; Hypotrichosis simplex. DR Orphanet; 98994; Total early-onset cataract. DR VEuPathDB; HostDB:ENSG00000160285; -. DR eggNOG; KOG0497; Eukaryota. DR GeneTree; ENSGT00390000011570; -. DR HOGENOM; CLU_009074_2_1_1; -. DR InParanoid; P48449; -. DR OMA; CWARQTI; -. DR OrthoDB; 21502at2759; -. DR PAN-GO; P48449; 3 GO annotations based on evolutionary models. DR PhylomeDB; P48449; -. DR BioCyc; MetaCyc:HS08480-MONOMER; -. DR BRENDA; 5.4.99.7; 2681. DR PathwayCommons; P48449; -. DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). DR Reactome; R-HSA-9969896; Lanosterol biosynthesis. DR SignaLink; P48449; -. DR UniPathway; UPA00767; UER00753. DR Agora; ENSG00000160285; -. DR BioGRID-ORCS; 4047; 44 hits in 1173 CRISPR screens. DR ChiTaRS; LSS; human. DR EvolutionaryTrace; P48449; -. DR GeneWiki; Lanosterol_synthase; -. DR GenomeRNAi; 4047; -. DR Pharos; P48449; Tchem. DR PRO; PR:P48449; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P48449; protein. DR Bgee; ENSG00000160285; Expressed in mucosa of stomach and 98 other cell types or tissues. DR ExpressionAtlas; P48449; baseline and differential. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0000250; F:lanosterol synthase activity; IMP:UniProtKB. DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:BHF-UCL. DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; IEA:Ensembl. DR GO; GO:0033490; P:cholesterol biosynthetic process via lathosterol; IEA:Ensembl. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:0006694; P:steroid biosynthetic process; IMP:UniProtKB. DR GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro. DR GO; GO:0036197; P:zymosterol biosynthetic process; IEA:Ensembl. DR CDD; cd02892; SQCY_1; 1. DR FunFam; 1.50.10.20:FF:000002; Terpene cyclase/mutase family member; 1. DR FunFam; 1.50.10.20:FF:000003; Terpene cyclase/mutase family member; 1. DR Gene3D; 1.50.10.20; -; 2. DR Gene3D; 6.20.120.20; -; 1. DR InterPro; IPR032696; SQ_cyclase_C. DR InterPro; IPR032697; SQ_cyclase_N. DR InterPro; IPR018333; Squalene_cyclase. DR InterPro; IPR002365; Terpene_synthase_CS. DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase. DR NCBIfam; TIGR01787; squalene_cyclas; 1. DR PANTHER; PTHR11764:SF20; LANOSTEROL SYNTHASE; 1. DR PANTHER; PTHR11764; TERPENE CYCLASE/MUTASE FAMILY MEMBER; 1. DR Pfam; PF13243; SQHop_cyclase_C; 1. DR Pfam; PF13249; SQHop_cyclase_N; 1. DR SFLD; SFLDG01016; Prenyltransferase_Like_2; 1. DR SUPFAM; SSF48239; Terpenoid cyclases/Protein prenyltransferases; 2. DR PROSITE; PS01074; TERPENE_SYNTHASES; 1. DR PDBsum; 1W6J; -. DR PDBsum; 1W6K; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cataract; KW Direct protein sequencing; Disease variant; Endoplasmic reticulum; KW Hypotrichosis; Intellectual disability; Isomerase; Lipid biosynthesis; KW Lipid metabolism; Membrane; Proteomics identification; Reference proteome; KW Repeat; Steroid biosynthesis. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:14766201, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..732 FT /note="Lanosterol synthase" FT /id="PRO_0000072659" FT REPEAT 77..121 FT /note="PFTB 1" FT /evidence="ECO:0000255" FT REPEAT 124..165 FT /note="PFTB 2" FT /evidence="ECO:0000255" FT REPEAT 424..468 FT /note="PFTB 3" FT /evidence="ECO:0000255" FT REPEAT 483..528 FT /note="PFTB 4" FT /evidence="ECO:0000255" FT REPEAT 560..600 FT /note="PFTB 5" FT /evidence="ECO:0000255" FT REPEAT 612..653 FT /note="PFTB 6" FT /evidence="ECO:0000255" FT REPEAT 670..712 FT /note="PFTB 7" FT /evidence="ECO:0000255" FT ACT_SITE 455 FT /note="Proton donor" FT /evidence="ECO:0000305|PubMed:15525992" FT SITE 387 FT /note="Transition state stabilizer" FT /evidence="ECO:0000269|PubMed:15525992" FT SITE 444 FT /note="Transition state stabilizer" FT /evidence="ECO:0000269|PubMed:15525992" FT SITE 581 FT /note="Transition state stabilizer" FT /evidence="ECO:0000269|PubMed:15525992" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:22814378" FT VAR_SEQ 1..80 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_045407" FT VAR_SEQ 133..143 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046188" FT VARIANT 12 FT /note="G -> D (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084019" FT VARIANT 14 FT /note="Y -> C (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084020" FT VARIANT 102 FT /note="L -> V (in HYPT14; the protein is present in the ER FT but also mislocalized to the cytoplasm)" FT /evidence="ECO:0000269|PubMed:30401459" FT /id="VAR_081921" FT VARIANT 141..732 FT /note="Missing (in APMR4; loss of protein expression)" FT /evidence="ECO:0000269|PubMed:30401459" FT /id="VAR_081922" FT VARIANT 175 FT /note="R -> Q (in dbSNP:rs2839158)" FT /id="VAR_024648" FT VARIANT 209 FT /note="N -> Y (in APMR4; changed localization; the protein FT is present in the ER but is also mislocalized to the FT cytoplasm; dbSNP:rs754230211)" FT /evidence="ECO:0000269|PubMed:30401459" FT /id="VAR_081923" FT VARIANT 248 FT /note="L -> P (in HYPT14; changed localization; the protein FT is present in the ER but is also mislocalized to the FT cytoplasm; dbSNP:rs1260995701)" FT /evidence="ECO:0000269|PubMed:30401459" FT /id="VAR_081924" FT VARIANT 260 FT /note="R -> P (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084021" FT VARIANT 286 FT /note="Y -> C (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084022" FT VARIANT 310 FT /note="H -> R (in dbSNP:rs34115287)" FT /id="VAR_052057" FT VARIANT 342 FT /note="I -> S (in CTRCT44; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29016354" FT /id="VAR_084023" FT VARIANT 391 FT /note="F -> S (in HYPT14; changed localization; the protein FT is present in the ER but is also mislocalized to the FT cytoplasm; dbSNP:rs1249530918)" FT /evidence="ECO:0000269|PubMed:30401459" FT /id="VAR_081925" FT VARIANT 516 FT /note="N -> S (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084024" FT VARIANT 581 FT /note="W -> R (in CTRCT44; loss of lanosterol synthase FT activity; dbSNP:rs864622780)" FT /evidence="ECO:0000269|PubMed:26200341" FT /id="VAR_075664" FT VARIANT 588 FT /note="G -> S (in CTRCT44; loss of lanosterol synthase FT activity; dbSNP:rs561449819)" FT /evidence="ECO:0000269|PubMed:26200341" FT /id="VAR_075665" FT VARIANT 604..732 FT /note="Missing (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084025" FT VARIANT 614 FT /note="R -> W (in dbSNP:rs35785446)" FT /id="VAR_052058" FT VARIANT 629 FT /note="W -> C (in CTRCT44; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29016354" FT /id="VAR_084026" FT VARIANT 642 FT /note="L -> V (in dbSNP:rs2254524)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5" FT /id="VAR_021522" FT VARIANT 652 FT /note="T -> I (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084027" FT VARIANT 688 FT /note="P -> L (in dbSNP:rs17293705)" FT /id="VAR_052059" FT VARIANT 705 FT /note="T -> K (in APMR4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30723320" FT /id="VAR_084028" FT CONFLICT 348 FT /note="W -> R (in Ref. 4; CAB42828)" FT /evidence="ECO:0000305" FT HELIX 22..24 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 25..30 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 33..38 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 40..45 FT /evidence="ECO:0007829|PDB:1W6J" FT HELIX 46..49 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 50..56 FT /evidence="ECO:0007829|PDB:1W6K" FT TURN 61..63 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 73..85 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 101..103 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 104..115 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:1W6J" FT HELIX 123..134 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 151..163 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 171..182 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 191..199 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 213..217 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 231..245 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 254..260 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 268..270 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 274..276 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 288..290 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 291..305 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 309..330 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 337..351 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 356..363 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 366..368 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 369..372 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 375..378 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 385..398 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 401..403 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 405..407 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 408..421 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 430..433 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 435..437 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 443..445 FT /evidence="ECO:0007829|PDB:1W6K" FT TURN 447..449 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 454..470 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 477..479 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 480..491 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 502..504 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 510..515 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 531..547 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 553..570 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 580..584 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 585..598 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 610..620 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 634..638 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 649..661 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 667..680 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 694..696 FT /evidence="ECO:0007829|PDB:1W6K" FT TURN 697..699 FT /evidence="ECO:0007829|PDB:1W6K" FT STRAND 700..702 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 707..722 FT /evidence="ECO:0007829|PDB:1W6K" FT HELIX 727..729 FT /evidence="ECO:0007829|PDB:1W6K" SQ SEQUENCE 732 AA; 83309 MW; E4708A5AE53585ED CRC64; MTEGTCLRRR GGPYKTEPAT DLGRWRLNCE RGRQTWTYLQ DERAGREQTG LEAYALGLDT KNYFKDLPKA HTAFEGALNG MTFYVGLQAE DGHWTGDYGG PLFLLPGLLI TCHVARIPLP AGYREEIVRY LRSVQLPDGG WGLHIEDKST VFGTALNYVS LRILGVGPDD PDLVRARNIL HKKGGAVAIP SWGKFWLAVL NVYSWEGLNT LFPEMWLFPD WAPAHPSTLW CHCRQVYLPM SYCYAVRLSA AEDPLVQSLR QELYVEDFAS IDWLAQRNNV APDELYTPHS WLLRVVYALL NLYEHHHSAH LRQRAVQKLY EHIVADDRFT KSISIGPISK TINMLVRWYV DGPASTAFQE HVSRIPDYLW MGLDGMKMQG TNGSQIWDTA FAIQALLEAG GHHRPEFSSC LQKAHEFLRL SQVPDNPPDY QKYYRQMRKG GFSFSTLDCG WIVSDCTAEA LKAVLLLQEK CPHVTEHIPR ERLCDAVAVL LNMRNPDGGF ATYETKRGGH LLELLNPSEV FGDIMIDYTY VECTSAVMQA LKYFHKRFPE HRAAEIRETL TQGLEFCRRQ QRADGSWEGS WGVCFTYGTW FGLEAFACMG QTYRDGTACA EVSRACDFLL SRQMADGGWG EDFESCEERR YLQSAQSQIH NTCWAMMGLM AVRHPDIEAQ ERGVRCLLEK QLPNGDWPQE NIAGVFNKSC AISYTSYRNI FPIWALGRFS QLYPERALAG HP //