LSS_MOUSE
ID LSS_MOUSE Reviewed; 733 AA.
AC Q8BLN5; Q8BVJ4; Q8K307;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Lanosterol synthase;
DE EC=5.4.99.7 {ECO:0000250|UniProtKB:P48449};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase;
DE AltName: Full=Oxidosqualene--lanosterol cyclase;
DE Short=OSC;
GN Name=Lss {ECO:0000312|EMBL:AAH29082.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|EMBL:AAH29082.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor {ECO:0000312|EMBL:AAH29082.1};
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Through the production of lanosterol may
CC regulate lens protein aggregation and increase transparency.
CC {ECO:0000250|UniProtKB:P48449}.
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:0000250|UniProtKB:P48449};
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 -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC {ECO:0000250|UniProtKB:P48450}.
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DR EMBL; AK044016; BAC31739.1; -; mRNA.
DR EMBL; AK078023; BAC37102.1; -; mRNA.
DR EMBL; BC029082; AAH29082.1; -; mRNA.
DR CCDS; CCDS23948.1; -.
DR RefSeq; NP_666118.1; NM_146006.2.
DR AlphaFoldDB; Q8BLN5; -.
DR SMR; Q8BLN5; -.
DR BioGRID; 201212; 3.
DR IntAct; Q8BLN5; 1.
DR MINT; Q8BLN5; -.
DR STRING; 10090.ENSMUSP00000046856; -.
DR iPTMnet; Q8BLN5; -.
DR PhosphoSitePlus; Q8BLN5; -.
DR SwissPalm; Q8BLN5; -.
DR EPD; Q8BLN5; -.
DR jPOST; Q8BLN5; -.
DR MaxQB; Q8BLN5; -.
DR PaxDb; Q8BLN5; -.
DR PeptideAtlas; Q8BLN5; -.
DR PRIDE; Q8BLN5; -.
DR ProteomicsDB; 275470; -.
DR Antibodypedia; 24599; 163 antibodies from 28 providers.
DR DNASU; 16987; -.
DR Ensembl; ENSMUST00000048678; ENSMUSP00000046856; ENSMUSG00000033105.
DR GeneID; 16987; -.
DR KEGG; mmu:16987; -.
DR UCSC; uc007fuq.2; mouse.
DR CTD; 4047; -.
DR MGI; MGI:1336155; Lss.
DR VEuPathDB; HostDB:ENSMUSG00000033105; -.
DR eggNOG; KOG0497; Eukaryota.
DR GeneTree; ENSGT00390000011570; -.
DR HOGENOM; CLU_009074_2_1_1; -.
DR InParanoid; Q8BLN5; -.
DR OMA; CWARQTI; -.
DR OrthoDB; 365003at2759; -.
DR PhylomeDB; Q8BLN5; -.
DR TreeFam; TF300406; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR SABIO-RK; Q8BLN5; -.
DR UniPathway; UPA00767; UER00753.
DR BioGRID-ORCS; 16987; 4 hits in 60 CRISPR screens.
DR ChiTaRS; Lss; mouse.
DR PRO; PR:Q8BLN5; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BLN5; protein.
DR Bgee; ENSMUSG00000033105; Expressed in embryonic brain and 284 other tissues.
DR ExpressionAtlas; Q8BLN5; baseline and differential.
DR Genevisible; Q8BLN5; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR GO; GO:0000250; F:lanosterol synthase activity; ISS:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0006694; P:steroid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; ISO:MGI.
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; Endoplasmic reticulum; Isomerase; Lipid biosynthesis;
KW 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_0000072660"
FT REPEAT 125..166
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 484..529
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT REPEAT 561..601
FT /note="PFTB 3"
FT /evidence="ECO:0000255"
FT REPEAT 613..654
FT /note="PFTB 4"
FT /evidence="ECO:0000255"
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 297
FT /note="V -> A (in Ref. 1; BAC37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="V -> A (in Ref. 1; BAC31739)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 733 AA; 83141 MW; 17C3ED638C0D66B0 CRC64;
MTEGTCLRRR GGPYKTEPAT DLTRWRLQNE LGRQRWTYYQ AEDDPGREQT GLEAHSLGLD
TRSYFTDLPK AQTAHEGALN GVTFYAKLQA EDGHWAGDYG GPLFLLPGLL ITCHISHISL
PAGYREEMVR YLRSVQLPDG GWGLHIEDKS TVFGTALNYV ALRILGIGPD DPDLVRARNV
LHKKGGAVAI PSWGKFWLAV LNVYSWEGLN TLFPEMWLFP EWVPAHPSTL WCHCRQVYLP
MSYCYATRLS ASEDPLVQSL RQELYVQDYA SIDWPAQRNN VSPDEMYTPH SWLLHVVYGL
LNLYERFHST SLRKWAVQML YEHIAADDCF TKCISIGPIS KTINMLVRWS VDGPSSPAFQ
EHVSRIKDYL WLGLDGMKMQ GTNGSQIWDT SFAIQALLEA GAHHRPEFLP CLQKAHEFLR
LSQVPENCPD YQKYYRHMRK GGFSFSTLDC GWIVADCTAE GLKAVLLLQN QCPSITEHIP
RERLCDAVDV LLSLRNADGG FATYEKKRGG YLLELLNPSE VFGDIMIDYT YVECTSAVMQ
ALKHFHEHFP DYRAAEVRET LNQGLDFCRR KQRADGSWEG SWGVCFTYGT WFGLEAFACM
GHTYQDGAAC AEVAQACNFL LSQQMADGGW GEDFESCEQR RYVQSARSQV HSTCWALMGL
MAVRHPDITA QERGIRCLLG KQLPNGDWPQ ENISGVFNKS CAISYTSYRN IFPIWALGRF
SNLYPDNTLA GHI
