ID   LSS_BOVIN               Reviewed;         732 AA.
AC   P84466; Q2EMV7;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 95.
DE   RecName: Full=Lanosterol synthase;
DE            EC=5.4.99.7 {ECO:0000269|PubMed:14678783};
DE   AltName: Full=2,3-epoxysqualene--lanosterol cyclase;
DE   AltName: Full=Oxidosqualene--lanosterol cyclase;
DE            Short=OSC;
GN   Name=LSS;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Chang C.-H., Huang C.-Y., Ko C.-Y., Wu T.-K.;
RT   "Molecular cloning and active-site mapping of oxidosqualene-lanosterol
RT   cyclase from bovine liver.";
RL   Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000305}
RP   PROTEIN SEQUENCE OF 163-174; 247-258 AND 493-506, FUNCTION, CATALYTIC
RP   ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Liver {ECO:0000269|PubMed:14678783};
RX   PubMed=14678783; DOI=10.1016/j.abb.2003.09.036;
RA   Wu T.-K., Huang C.-Y., Ko C.-Y., Chang C.-H., Chen Y.-J., Liao H.-K.;
RT   "Purification, tandem mass characterization, and inhibition studies of
RT   oxidosqualene-lanosterol cyclase enzyme from bovine liver.";
RL   Arch. Biochem. Biophys. 421:42-53(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:14678783). 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:14678783}.
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:14678783};
CC   -!- ACTIVITY REGULATION: Inhibited by the benzophenone containing OSC
CC       inhibitor Ro48-8071 and to a lesser extent by other benzophene
CC       containing inhibitors. {ECO:0000269|PubMed:14678783}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=11 uM for (3S)-2,3-oxidosqualine {ECO:0000269|PubMed:14678783};
CC       pH dependence:
CC         Optimum pH is 7.4. Active from pH 5.0 to 10.0.
CC         {ECO:0000269|PubMed:14678783};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius. Active from 25 to 50
CC         degrees Celsius. {ECO:0000269|PubMed:14678783};
CC   -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC       farnesyl diphosphate: step 3/3. {ECO:0000269|PubMed:14678783}.
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   -!- TISSUE SPECIFICITY: Detected in the liver (at protein level).
CC       {ECO:0000269|PubMed:14678783}.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC       {ECO:0000250|UniProtKB:P48449}.
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DR   EMBL; DQ372933; ABD24094.1; -; mRNA.
DR   RefSeq; NP_001040029.1; NM_001046564.1.
DR   AlphaFoldDB; P84466; -.
DR   SMR; P84466; -.
DR   STRING; 9913.ENSBTAP00000025201; -.
DR   PaxDb; 9913-ENSBTAP00000025201; -.
DR   GeneID; 615906; -.
DR   KEGG; bta:615906; -.
DR   eggNOG; KOG0497; Eukaryota.
DR   InParanoid; P84466; -.
DR   SABIO-RK; P84466; -.
DR   UniPathway; UPA00767; UER00753.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR   GO; GO:0000250; F:lanosterol synthase activity; IDA:UniProtKB.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0006694; P:steroid biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR   CDD; cd02892; SQCY_1; 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.
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..732
FT                   /note="Lanosterol synthase"
FT                   /id="PRO_0000072658"
FT   REPEAT          124..165
FT                   /note="PFTB 1"
FT   REPEAT          483..528
FT                   /note="PFTB 2"
FT   REPEAT          560..600
FT                   /note="PFTB 3"
FT   REPEAT          612..663
FT                   /note="PFTB 4"
FT   REPEAT          670..712
FT                   /note="PFTB 5"
FT   ACT_SITE        455
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   MOD_RES         2
FT                   /note="N-acetylthreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
SQ   SEQUENCE   732 AA;  83184 MW;  B06289C2FE03B4B2 CRC64;
     MTEGTCLRRR GGPYKTEPAT DLSRWRLSNQ VGRQTWTYSQ EEDPVREQSG LEAHLLGLDT
     KSFFKDLPKA HTACRGALNG VTFYAALQTE DGHWAGDYGG PLFLLPGLLI TCHVANIPLP
     AGYREEIIRY LRSVQLPDGG WGLHIEDKST VFGTALNYVS LRILGVGPDD PDLVRARNLL
     HKKGGAVFIP SWGKFWLAVL NVYSWEGLNT LFPEMWLFPD WMPAHPSTIW CHCRQVYLPM
     AYCYSTRLSA EEGPLVQSLR QELYLEDYSC IDWAAHRNSV APDDLYTPHS WLLHVVYAIL
     NLYERHHSTS LRQWATQKLY EHIAADDRFT KCISIGPISK TINMLVRWHV DGPASAVFQE
     HVSRIPDYLW LGLDGMKMQG TNGSQIWDTA FAIQALLEAR AQHRPEFWSC LRKAHEYLRI
     SQVPDNFPDY QKYYRHMSKG GFSFSTLDCG WIVADCTAEA LKSILLLQEK CPFVSNHVPR
     ERLFDTVAVL LSLRNPDGGF ATYETKRGGH LLELLNPSEV FGDIMIDYTY VECTSAVMQA
     LKTFHKQFPD HRAGEIRETL EQGLQFCRQK QRPDGSWEGS WGVCFTYGAW FGLEAFACMG
     HTYHNGVACA EISRACDFLL SRQMADGGWG EDFESCKQRR YVQSAQSQIH NTCWALMGLM
     AVRHPDVAAL ERGVSYLLEK QLPNGDWPQE NISGVFNKSC AISYTSYRNV FPIWTLGRFS
     RLHPDPALAG HP
//