LSS_RAT
ID LSS_RAT Reviewed; 733 AA.
AC P48450; Q62811;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Lanosterol synthase;
DE EC=5.4.99.7 {ECO:0000269|PubMed:7568116};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase;
DE AltName: Full=Oxidosqualene--lanosterol cyclase;
DE Short=OSC;
GN Name=Lss; Synonyms=Osc;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-154; 279-287 AND
RP 439-470, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7568116; DOI=10.1073/pnas.92.20.9274;
RA Abe I., Prestwich G.D.;
RT "Molecular cloning, characterization, and functional expression of rat
RT oxidosqualene cyclase cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:9274-9278(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7735243; DOI=10.1248/bpb.18.195;
RA Kusano M., Shibuya M., Sankawa U., Ebizuka Y.;
RT "Molecular cloning of cDNA encoding rat 2,3-oxidosqualene: lanosterol
RT cyclase.";
RL Biol. Pharm. Bull. 18:195-197(1995).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16440058; DOI=10.1172/jci20797;
RA Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T.,
RA Nishizono S., Serikawa T., Higuchi K., Shumiya S.;
RT "Lanosterol synthase mutations cause cholesterol deficiency-associated
RT cataracts in the Shumiya cataract rat.";
RL J. Clin. Invest. 116:395-404(2006).
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:7568116). Through the production of
CC lanosterol may regulate lens protein aggregation and increase
CC transparency (By similarity). {ECO:0000250|UniProtKB:P48449,
CC ECO:0000269|PubMed:7568116}.
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:7568116};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 3/3.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P48449}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P48449}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P48449}.
CC -!- DISRUPTION PHENOTYPE: Hypomorphic mutations in this gene and the Fdft1
CC gene were identified, as well as a null mutation in this gene. Cataract
CC onset is associated with the specific combination of Lss and Fdft1
CC mutant alleles that decrease cholesterol levels in cataractous lenses
CC to about 57% of normal. Cholesterol insufficiency may cause the
CC deficient proliferation of lens epithelial cells in Shumiya cataract
CC rats, resulting in the loss of homeostatic epithelial cell control of
CC the underlying fiber cells and ultimately cataractogenesis.
CC {ECO:0000269|PubMed:16440058}.
CC -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; U31352; AAA91023.1; -; mRNA.
DR EMBL; D45252; BAA08208.1; -; mRNA.
DR RefSeq; NP_112311.1; NM_031049.1.
DR AlphaFoldDB; P48450; -.
DR SMR; P48450; -.
DR BioGRID; 249578; 1.
DR STRING; 10116.ENSRNOP00000039946; -.
DR BindingDB; P48450; -.
DR ChEMBL; CHEMBL3262; -.
DR GuidetoPHARMACOLOGY; 2434; -.
DR iPTMnet; P48450; -.
DR PhosphoSitePlus; P48450; -.
DR jPOST; P48450; -.
DR PRIDE; P48450; -.
DR GeneID; 81681; -.
DR KEGG; rno:81681; -.
DR UCSC; RGD:620955; rat.
DR CTD; 4047; -.
DR RGD; 620955; Lss.
DR eggNOG; KOG0497; Eukaryota.
DR InParanoid; P48450; -.
DR OrthoDB; 365003at2759; -.
DR PhylomeDB; P48450; -.
DR BRENDA; 5.4.99.7; 5301.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR SABIO-RK; P48450; -.
DR UniPathway; UPA00767; UER00753.
DR PRO; PR:P48450; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005811; C:lipid droplet; ISO:RGD.
DR GO; GO:0000250; F:lanosterol synthase activity; IDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; ISO:RGD.
DR GO; GO:0016125; P:sterol metabolic process; IMP:RGD.
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 Acetylation; Direct protein sequencing; Endoplasmic reticulum; Isomerase;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Reference proteome; Repeat;
KW Steroid biosynthesis.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT CHAIN 2..733
FT /note="Lanosterol synthase"
FT /id="PRO_0000072661"
FT REPEAT 125..166
FT /note="PFTB 1"
FT REPEAT 484..529
FT /note="PFTB 2"
FT REPEAT 561..601
FT /note="PFTB 3"
FT REPEAT 613..654
FT /note="PFTB 4"
FT ACT_SITE 456
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT CONFLICT 139
FT /note="D -> N (in Ref. 1; AAA91023)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="A -> G (in Ref. 2; BAA08208)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="R -> Q (in Ref. 2; BAA08208)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="D -> N (in Ref. 2; BAA08208)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="S -> I (in Ref. 1; AAA91023)"
FT /evidence="ECO:0000305"
FT CONFLICT 683
FT /note="L -> F (in Ref. 2; BAA08208)"
FT /evidence="ECO:0000305"
FT CONFLICT 687
FT /note="D -> E (in Ref. 2; BAA08208)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 733 AA; 83301 MW; 3679C0259CBDF771 CRC64;
MTEGTCLRRR GGPYKTEPAT DLTRWRLHNE LGRQRWTYYQ AEEDPGREQT GLEAHSLGLD
TTSYFKNLPK AQTAHEGALN GVTFYAKLQA EDGHWAGDYG GPLFLLPGLL ITCHIAHIPL
PAGYREEMVR YLRSVQLPDG GWGLHIEDKS TVFGTALSYV SLRILGIGPD DPDLVRARNI
LHKKGGAVAI PSWGKFWLAV LNVYSWEGIN TLFPEMWLLP EWFPAHPSTL WCHCRQVYLP
MSYCYATRLS ASEDPLVQSL RQELYVEDYA SIDWPAQKNN VCPDDMYTPH SWLLHVVYGL
LNLYERFHST SLRKWAIQLL YEHVAADDRF TKCISIGPIS KTVNMLIRWS VDGPSSPAFQ
EHVSRIKDYL WLGLDGMKMQ GTNGSQTWDT SFAVQALLEA GAHRRPEFLP CLQKAHEFLR
LSQVPDNNPD YQKYYRHMHK GGFPFSTLDC GWIVADCTAE ALKAVLLLQE RCPSITEHVP
RERLYDAVAV LLSMRNSDGG FATYETKRGG YLLELLNPSE VFGDIMIDYT YVECTSAVMQ
ALRHFREYFP DHRATESRET LNQGLDFCRK KQRADGSWEG SWGVCFTYGT WFGLEAFACM
GHIYQNRTAC AEVAQACHFL LSRQMADGGW GEDFESCEQR RYVQSAGSQV HSTCWALLGL
MAVRHPDISA QERGIRCLLG KQLPNGDWPQ ENISGVFNKS CAISYTNYRN IFPIWALGRF
SSLYPDNTLA GHI
