Lanosterol synthase (LSS)
The protein contains 732 amino acids for an estimated molecular weight of 83309 Da.
Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus (PubMed:14766201, PubMed:7639730, PubMed:26200341). Through the production of lanosterol may regulate lens protein aggregation and increase transparency (PubMed:26200341). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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No binding partner found
The reference OMIM entry for this protein is 600909
Lanosterol synthase; lss
2,3-@oxidosqualene-lanosterol cyclase; osc
DESCRIPTION
Lanosterol synthase (EC 5.4.99.7) catalyzes the cyclization step in the biosynthesis of cholesterol (summary by Roessler et al., 1999).CLONING
Baker et al. (1995) cloned and characterized the human gene encoding lanosterol synthase, which they called OSC, and found that it predicts an 83-kD protein of 732 amino acids. The deduced amino acid sequence is 36 to 40% identical to known yeast and plant homologs and 83% identical to rat lanosterol synthase. A yeast lanosterol synthase-deficient mutant was complemented by the human gene, and a cell-free homogenate of the yeast mutant strain expressed in the human gene was shown to convert 2,3-oxidosqualene to lanosterol.MAPPING
Using exon trapping to identify portions of genes on human chromosome 21, Young et al. (1996) identified coding regions with strong homology to the lanosterol synthase gene of rat and yeast. They mapped the human LSS gene to 21q22.3 between marker D21S25 and 21qter using somatic cell hybrids and chromosome-21 YACs and cosmids. They also cloned a portion of the human cDNA from a brain cDNA library and determined its nucleotide sequence. Roessler et al. (1999) reported the complete structure of the human LSS gene, which contains 23 exons.BIOCHEMICAL FEATURES
- Crystal Structure Thoma et al. (2004) presented 2 crystal structures of the human membrane protein lanosterol synthase: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction. Thoma et al. (2004) found that human OSC consists of 2 alpha/alpha barrel domains that are connected by loops and 3 smaller beta-structures. The large active site cavity is located in the center of the molecule between domains 1 and 2. The N-terminal OSC region, which is absent from other cyclase sequences, fills the space between the 2 domains and could function in stabilizing the relative orientations. Human OSC is monomeric in the crystal, which is consistent with analytic ultracentrifuge data.ANIMAL MODEL
By positional cloning and genotyping in Shumiya cataract rats, Mori et al. (2006) identified hypomorphic mutations in the Lss gene and the Fdft1 gene (184420), as well as a null mutation in Lss. Cataract onset was associated with the specific combination of Lss and Fdft1 mutant alleles that decreased cholesterol levels in cataractous lenses to about 57% of normal. Mori et al. (2006) concluded that cholesterol insufficiency may cause the deficient proliferation of lens epithelial cells in Shumiya cataract rats, resulting in the loss of homeostatic epithelial cell control of the underlying fiber cells and ultimately cataractogenesis.HISTORY
Roessler et al. (1999) presented the results of a mutation analysis in patients with holoprosencephaly, one form of which, HPE1 (236100), maps to the same interval as LSS on chromosome 21. LSS was considered an excellent candidate gene for HPE because of the requirement for cholesterol modification of the Sonic hedgehog protein (SHH; 600725), an HPE-associated protein, for correct patterning activity. Despite an extensive pedigree analysis of numerous polymorphisms, as well as complementation studies in yeast on one of the missense mutations, Roessler et al. (1999 ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 600909 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).