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Protein

Lanosterol synthase

Gene

Lss

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Through the production of lanosterol may regulate lens protein aggregation and increase transparency.By similarity1 Publication

Catalytic activityi

(3S)-2,3-epoxy-2,3-dihydrosqualene = lanosterol.1 Publication

Pathwayi: lanosterol biosynthesis

This protein is involved in step 3 of the subpathway that synthesizes lanosterol from farnesyl diphosphate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Squalene synthase (Fdft1)
  2. Squalene monooxygenase (Sqle)
  3. Lanosterol synthase (Lss)
This subpathway is part of the pathway lanosterol biosynthesis, which is itself part of Terpene metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes lanosterol from farnesyl diphosphate, the pathway lanosterol biosynthesis and in Terpene metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei233 – 2331Proton acceptorBy similarity
Active sitei456 – 4561Proton donorBy similarity

GO - Molecular functioni

  • lanosterol synthase activity Source: RGD

GO - Biological processi

  • cholesterol biosynthetic process Source: RGD
  • sterol metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis

Enzyme and pathway databases

BRENDAi5.4.99.7. 5301.
SABIO-RKP48450.
UniPathwayiUPA00767; UER00753.

Names & Taxonomyi

Protein namesi
Recommended name:
Lanosterol synthase (EC:5.4.99.7)
Alternative name(s):
2,3-epoxysqualene--lanosterol cyclase
Oxidosqualene--lanosterol cyclase
Short name:
OSC
Gene namesi
Name:Lss
Synonyms:Osc
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620955. Lss.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Hypomorphic mutations in this gene and the Fdft1 gene were identified, as well as a null mutation in this gene. Cataract onset is associated with the specific combination of Lss and Fdft1 mutant alleles that decrease cholesterol levels in cataractous lenses to about 57% of normal. 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.1 Publication

Chemistry

ChEMBLiCHEMBL3262.
GuidetoPHARMACOLOGYi2434.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 733732Lanosterol synthasePRO_0000072661Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PRIDEiP48450.

PTM databases

PhosphoSiteiP48450.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

BioGridi249578. 1 interaction.
MINTiMINT-4569823.

Chemistry

BindingDBiP48450.

Structurei

3D structure databases

ProteinModelPortaliP48450.
SMRiP48450. Positions 6-732.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati125 – 16642PFTB 1Add
BLAST
Repeati484 – 52946PFTB 2Add
BLAST
Repeati561 – 60141PFTB 3Add
BLAST
Repeati613 – 65442PFTB 4Add
BLAST

Sequence similaritiesi

Belongs to the terpene cyclase/mutase family.Curated
Contains 4 PFTB repeats.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

HOGENOMiHOG000234317.
HOVERGENiHBG005604.
InParanoidiP48450.
KOiK01852.
PhylomeDBiP48450.

Family and domain databases

Gene3Di1.50.10.20. 2 hits.
InterProiIPR032696. SQ_cyclase_C.
IPR032697. SQ_cyclase_N.
IPR018333. Squalene_cyclase.
IPR002365. Terpene_synthase_CS.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamiPF13243. SQHop_cyclase_C. 1 hit.
PF13249. SQHop_cyclase_N. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 2 hits.
TIGRFAMsiTIGR01787. squalene_cyclas. 1 hit.
PROSITEiPS01074. TERPENE_SYNTHASES. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P48450-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEGTCLRRR GGPYKTEPAT DLTRWRLHNE LGRQRWTYYQ AEEDPGREQT
60 70 80 90 100
GLEAHSLGLD TTSYFKNLPK AQTAHEGALN GVTFYAKLQA EDGHWAGDYG
110 120 130 140 150
GPLFLLPGLL ITCHIAHIPL PAGYREEMVR YLRSVQLPDG GWGLHIEDKS
160 170 180 190 200
TVFGTALSYV SLRILGIGPD DPDLVRARNI LHKKGGAVAI PSWGKFWLAV
210 220 230 240 250
LNVYSWEGIN TLFPEMWLLP EWFPAHPSTL WCHCRQVYLP MSYCYATRLS
260 270 280 290 300
ASEDPLVQSL RQELYVEDYA SIDWPAQKNN VCPDDMYTPH SWLLHVVYGL
310 320 330 340 350
LNLYERFHST SLRKWAIQLL YEHVAADDRF TKCISIGPIS KTVNMLIRWS
360 370 380 390 400
VDGPSSPAFQ EHVSRIKDYL WLGLDGMKMQ GTNGSQTWDT SFAVQALLEA
410 420 430 440 450
GAHRRPEFLP CLQKAHEFLR LSQVPDNNPD YQKYYRHMHK GGFPFSTLDC
460 470 480 490 500
GWIVADCTAE ALKAVLLLQE RCPSITEHVP RERLYDAVAV LLSMRNSDGG
510 520 530 540 550
FATYETKRGG YLLELLNPSE VFGDIMIDYT YVECTSAVMQ ALRHFREYFP
560 570 580 590 600
DHRATESRET LNQGLDFCRK KQRADGSWEG SWGVCFTYGT WFGLEAFACM
610 620 630 640 650
GHIYQNRTAC AEVAQACHFL LSRQMADGGW GEDFESCEQR RYVQSAGSQV
660 670 680 690 700
HSTCWALLGL MAVRHPDISA QERGIRCLLG KQLPNGDWPQ ENISGVFNKS
710 720 730
CAISYTNYRN IFPIWALGRF SSLYPDNTLA GHI
Length:733
Mass (Da):83,301
Last modified:March 29, 2005 - v2
Checksum:i3679C0259CBDF771
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti139 – 1391D → N in AAA91023 (PubMed:7568116).Curated
Sequence conflicti189 – 1891A → G in BAA08208 (PubMed:7735243).Curated
Sequence conflicti481 – 4811R → Q in BAA08208 (PubMed:7735243).Curated
Sequence conflicti486 – 4861D → N in BAA08208 (PubMed:7735243).Curated
Sequence conflicti557 – 5571S → I in AAA91023 (PubMed:7568116).Curated
Sequence conflicti683 – 6831L → F in BAA08208 (PubMed:7735243).Curated
Sequence conflicti687 – 6871D → E in BAA08208 (PubMed:7735243).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U31352 mRNA. Translation: AAA91023.1.
D45252 mRNA. Translation: BAA08208.1.
RefSeqiNP_112311.1. NM_031049.1.
UniGeneiRn.10211.

Genome annotation databases

GeneIDi81681.
KEGGirno:81681.
UCSCiRGD:620955. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U31352 mRNA. Translation: AAA91023.1.
D45252 mRNA. Translation: BAA08208.1.
RefSeqiNP_112311.1. NM_031049.1.
UniGeneiRn.10211.

3D structure databases

ProteinModelPortaliP48450.
SMRiP48450. Positions 6-732.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249578. 1 interaction.
MINTiMINT-4569823.

Chemistry

BindingDBiP48450.
ChEMBLiCHEMBL3262.
GuidetoPHARMACOLOGYi2434.

PTM databases

PhosphoSiteiP48450.

Proteomic databases

PRIDEiP48450.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81681.
KEGGirno:81681.
UCSCiRGD:620955. rat.

Organism-specific databases

CTDi4047.
RGDi620955. Lss.

Phylogenomic databases

HOGENOMiHOG000234317.
HOVERGENiHBG005604.
InParanoidiP48450.
KOiK01852.
PhylomeDBiP48450.

Enzyme and pathway databases

UniPathwayiUPA00767; UER00753.
BRENDAi5.4.99.7. 5301.
SABIO-RKP48450.

Miscellaneous databases

NextBioi615300.
PROiP48450.

Family and domain databases

Gene3Di1.50.10.20. 2 hits.
InterProiIPR032696. SQ_cyclase_C.
IPR032697. SQ_cyclase_N.
IPR018333. Squalene_cyclase.
IPR002365. Terpene_synthase_CS.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamiPF13243. SQHop_cyclase_C. 1 hit.
PF13249. SQHop_cyclase_N. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 2 hits.
TIGRFAMsiTIGR01787. squalene_cyclas. 1 hit.
PROSITEiPS01074. TERPENE_SYNTHASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA."
    Abe I., Prestwich G.D.
    Proc. Natl. Acad. Sci. U.S.A. 92:9274-9278(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-154; 279-287 AND 439-470, FUNCTION, CATALYTIC ACTIVITY.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. "Molecular cloning of cDNA encoding rat 2,3-oxidosqualene: lanosterol cyclase."
    Kusano M., Shibuya M., Sankawa U., Ebizuka Y.
    Biol. Pharm. Bull. 18:195-197(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  3. "Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat."
    Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T., Nishizono S., Serikawa T., Higuchi K., Shumiya S.
    J. Clin. Invest. 116:395-404(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiERG7_RAT
AccessioniPrimary (citable) accession number: P48450
Secondary accession number(s): Q62811
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: March 29, 2005
Last modified: April 13, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.