LSS_HUMAN
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 03-AUG-2022, entry version 201.
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:7639730,
CC PubMed:26200341). Through the production of lanosterol may regulate
CC lens 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}.
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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_001001438.2. [P48449-1]
DR RefSeq; NP_001138908.1; NM_001145436.1. [P48449-3]
DR RefSeq; NP_001138909.1; NM_001145437.1. [P48449-2]
DR RefSeq; NP_002331.3; NM_002340.5. [P48449-1]
DR RefSeq; XP_016883835.1; XM_017028346.1.
DR RefSeq; XP_016883836.1; XM_017028347.1.
DR PDB; 1W6J; X-ray; 2.20 A; A=1-732.
DR PDB; 1W6K; X-ray; 2.10 A; A=1-732.
DR PDBsum; 1W6J; -.
DR PDBsum; 1W6K; -.
DR AlphaFoldDB; P48449; -.
DR SMR; P48449; -.
DR BioGRID; 110225; 57.
DR IntAct; P48449; 24.
DR MINT; P48449; -.
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 iPTMnet; P48449; -.
DR PhosphoSitePlus; P48449; -.
DR SwissPalm; P48449; -.
DR BioMuta; LSS; -.
DR DMDM; 1352387; -.
DR EPD; P48449; -.
DR jPOST; P48449; -.
DR MassIVE; P48449; -.
DR MaxQB; P48449; -.
DR PaxDb; P48449; -.
DR PeptideAtlas; P48449; -.
DR PRIDE; P48449; -.
DR ProteomicsDB; 19902; -.
DR ProteomicsDB; 34015; -.
DR ProteomicsDB; 55893; -. [P48449-1]
DR Antibodypedia; 24599; 163 antibodies from 28 providers.
DR DNASU; 4047; -.
DR Ensembl; ENST00000356396.8; ENSP00000348762.3; ENSG00000160285.15. [P48449-1]
DR Ensembl; ENST00000397728.8; ENSP00000380837.2; ENSG00000160285.15. [P48449-1]
DR Ensembl; ENST00000457828.6; ENSP00000409191.2; ENSG00000160285.15. [P48449-2]
DR Ensembl; ENST00000522411.5; ENSP00000429133.1; ENSG00000160285.15. [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 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 neXtProt; NX_P48449; -.
DR OpenTargets; ENSG00000160285; -.
DR Orphanet; 2850; Alopecia-intellectual disability syndrome.
DR Orphanet; 55654; Hypotrichosis simplex.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA30473; -.
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; 365003at2759; -.
DR PhylomeDB; P48449; -.
DR TreeFam; TF300406; -.
DR BioCyc; MetaCyc:HS08480-MON; -.
DR BRENDA; 5.4.99.7; 2681.
DR PathwayCommons; P48449; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR SignaLink; P48449; -.
DR UniPathway; UPA00767; UER00753.
DR BioGRID-ORCS; 4047; 37 hits in 1081 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 96 other tissues.
DR ExpressionAtlas; P48449; baseline and differential.
DR Genevisible; P48449; HS.
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: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 CDD; cd02892; SQCY_1; 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 PANTHER; PTHR11764; PTHR11764; 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; SSF48239; 2.
DR TIGRFAMs; TIGR01787; squalene_cyclas; 1.
DR PROSITE; PS01074; TERPENE_SYNTHASES; 1.
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; Reference proteome; Repeat;
KW 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30723320"
FT /id="VAR_084019"
FT VARIANT 14
FT /note="Y -> C (in APMR4; unknown pathological
FT 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30723320"
FT /id="VAR_084021"
FT VARIANT 286
FT /note="Y -> C (in APMR4; unknown pathological
FT 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; associated with hypotrichosis;
FT unknown pathological 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; unknown pathological
FT 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; unknown pathological
FT 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; associated with hypotrichosis;
FT unknown pathological 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; unknown pathological
FT 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; unknown pathological
FT 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 50..56
FT /evidence="ECO:0007829|PDB:1W6K"
FT TURN 61..63
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 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 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 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 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
