Lanosterol synthase

LSS
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1W6J, 1W6K
Identifiers
Aliases	LSS, OSC, CTRCT44, lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase), lanosterol synthase, HYPT14, APMR4
External IDs	OMIM: 600909; MGI: 1336155; HomoloGene: 37408; GeneCards: LSS; OMA:LSS - orthologs
Gene location (Human)
Chr.	Chromosome 21 (human)
End	46,228,824 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	76,392,972 bp
RNA expression pattern
	Top expressed in
	gastric mucosa; ; C1 segment; ; skin of leg; ; right ovary; ; skin of abdomen; ; corpus callosum; ; pituitary gland; ; right hemisphere of cerebellum; ; ventricular zone; ; left ovary;
	Top expressed in
	lip; ; epithelium of small intestine; ; skin of external ear; ; Ileal epithelium; ; Paneth cell; ; hair follicle; ; gastrula; ; transitional epithelium of urinary bladder; ; sciatic nerve; ; ciliary body;
	More reference expression data
	n/a
Gene ontology
Molecular function	isomerase activity; intramolecular transferase activity; lanosterol synthase activity; beta-amyrin synthase activity;
Cellular component	lipid droplet; endoplasmic reticulum membrane; endoplasmic reticulum; membrane;
Biological process	regulation of protein stability; lipid metabolism; steroid biosynthetic process; cholesterol biosynthetic process; regulation of cholesterol biosynthetic process; triterpenoid biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	4047
	16987
	ENSG00000160285; ENSG00000281289
	ENSMUSG00000033105
	P48449
	Q8BLN5
	NM_001001438; NM_001145436; NM_001145437; NM_002340
	NM_146006
	NP_001001438; NP_001138908; NP_001138909; NP_002331
	NP_666118
	Wikidata
View/Edit Human	View/Edit Mouse

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lanosterol synthase
lanosterol synthase
Identifiers
EC no.	5.4.99.7
CAS no.	9032-71-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
PMC
Search
PMC	articles
PubMed	articles
NCBI	proteins

Lanosterol synthase (EC 5.4.99.7) is an oxidosqualene cyclase (OSC) enzyme that converts (S)-2,3-oxidosqualene to a protosterol cation and finally to lanosterol.^[5] Lanosterol is a key four-ringed intermediate in cholesterol biosynthesis.^[6]^[7] In humans, lanosterol synthase is encoded by the LSS gene.^[8]^[9]

In eukaryotes, lanosterol synthase is an integral monotopic protein associated with the cytosolic side of the endoplasmic reticulum.^[10] Some evidence suggests that the enzyme is a soluble, non-membrane bound protein in the few prokaryotes that produce it.^[11]

Due to the enzyme's role in cholesterol biosynthesis, there is interest in lanosterol synthase inhibitors as potential cholesterol-reducing drugs, to complement existing statins.^[12]

^ ^a ^b ^c ENSG00000281289 GRCh38: Ensembl release 89: ENSG00000160285, ENSG00000281289 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033105 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Dean PD, Ortiz de Montellano PR, Bloch K, Corey EJ (Jun 1967). "A soluble 2,3-oxidosqualene sterol cyclase". The Journal of Biological Chemistry. 242 (12): 3014–5. doi:10.1016/S0021-9258(18)99606-7. PMID 6027261.
^ Huff MW, Telford DE (Jul 2005). "Lord of the rings--the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear". Trends in Pharmacological Sciences. 26 (7): 335–340. doi:10.1016/j.tips.2005.05.004. PMID 15951028.
^ Yamamoto S, Lin K, Bloch K (May 1969). "Some properties of the microsomal 2,3-oxidosqualene sterol cyclase". Proceedings of the National Academy of Sciences of the United States of America. 63 (1): 110–7. Bibcode:1969PNAS...63..110Y. doi:10.1073/pnas.63.1.110. PMC 534008. PMID 5257956.
^ Baker CH, Matsuda SP, Liu DR, Corey EJ (Aug 1995). "Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library". Biochemical and Biophysical Research Communications. 213 (1): 154–160. doi:10.1006/bbrc.1995.2110. PMID 7639730.
^ Young M, Chen H, Lalioti MD, Antonarakis SE (May 1996). "The human lanosterol synthase gene maps to chromosome 21q22.3". Human Genetics. 97 (5): 620–624. doi:10.1007/BF02281872. PMID 8655142. S2CID 21051816.
^ Ruf A, Müller F, D'Arcy B, Stihle M, Kusznir E, Handschin C, Morand OH, Thoma R (Mar 2004). "The monotopic membrane protein human oxidosqualene cyclase is active as monomer". Biochemical and Biophysical Research Communications. 315 (2): 247–254. doi:10.1016/j.bbrc.2004.01.052. PMID 14766201.
^ Lamb DC, Jackson CJ, Warrilow AG, Manning NJ, Kelly DE, Kelly SL (Aug 2007). "Lanosterol biosynthesis in the prokaryote Methylococcus capsulatus: insight into the evolution of sterol biosynthesis". Molecular Biology and Evolution. 24 (8): 1714–1721. doi:10.1093/molbev/msm090. PMID 17567593.
^ Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A (Nov 2004). "Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase". Nature. 432 (7013): 118–122. Bibcode:2004Natur.432..118T. doi:10.1038/nature02993. PMID 15525992. S2CID 364281.

[refGRCh38Ensembl-1] ENSG00000281289 GRCh38: Ensembl release 89: ENSG00000160285, ENSG00000281289 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000033105 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid6027261-5] Dean PD, Ortiz de Montellano PR, Bloch K, Corey EJ (Jun 1967). "A soluble 2,3-oxidosqualene sterol cyclase". The Journal of Biological Chemistry. 242 (12): 3014–5. doi:10.1016/S0021-9258(18)99606-7. PMID 6027261.

[one-6] Huff MW, Telford DE (Jul 2005). "Lord of the rings--the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear". Trends in Pharmacological Sciences. 26 (7): 335–340. doi:10.1016/j.tips.2005.05.004. PMID 15951028.

[nineteen-7] Yamamoto S, Lin K, Bloch K (May 1969). "Some properties of the microsomal 2,3-oxidosqualene sterol cyclase". Proceedings of the National Academy of Sciences of the United States of America. 63 (1): 110–7. Bibcode:1969PNAS...63..110Y. doi:10.1073/pnas.63.1.110. PMC 534008. PMID 5257956.

[pmid7639730-8] Baker CH, Matsuda SP, Liu DR, Corey EJ (Aug 1995). "Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library". Biochemical and Biophysical Research Communications. 213 (1): 154–160. doi:10.1006/bbrc.1995.2110. PMID 7639730.

[pmid8655142-9] Young M, Chen H, Lalioti MD, Antonarakis SE (May 1996). "The human lanosterol synthase gene maps to chromosome 21q22.3". Human Genetics. 97 (5): 620–624. doi:10.1007/BF02281872. PMID 8655142. S2CID 21051816.

[four-10] Ruf A, Müller F, D'Arcy B, Stihle M, Kusznir E, Handschin C, Morand OH, Thoma R (Mar 2004). "The monotopic membrane protein human oxidosqualene cyclase is active as monomer". Biochemical and Biophysical Research Communications. 315 (2): 247–254. doi:10.1016/j.bbrc.2004.01.052. PMID 14766201.

[eighteen-11] Lamb DC, Jackson CJ, Warrilow AG, Manning NJ, Kelly DE, Kelly SL (Aug 2007). "Lanosterol biosynthesis in the prokaryote Methylococcus capsulatus: insight into the evolution of sterol biosynthesis". Molecular Biology and Evolution. 24 (8): 1714–1721. doi:10.1093/molbev/msm090. PMID 17567593.

[three-12] Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A (Nov 2004). "Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase". Nature. 432 (7013): 118–122. Bibcode:2004Natur.432..118T. doi:10.1038/nature02993. PMID 15525992. S2CID 364281.

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