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Protein

Lanosterol synthase

Gene

LSS

Organism
Homo sapiens (Human)
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.2 Publications

Catalytic activityi

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

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)DescriptionActionsGraphical viewLength
Active sitei232Proton acceptor1
Active sitei455Proton donorCurated1

GO - Molecular functioni

  • lanosterol synthase activity Source: UniProtKB

GO - Biological processi

  • cholesterol biosynthetic process Source: BHF-UCL
  • regulation of protein stability Source: UniProtKB
  • steroid biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS08480-MONOMER.
ZFISH:HS08480-MONOMER.
BRENDAi5.4.99.7. 2681.
ReactomeiR-HSA-191273. Cholesterol biosynthesis.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
UniPathwayiUPA00767; UER00753.

Chemistry databases

SwissLipidsiSLP:000000646.
SLP:000001308. [P48449-1]

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
Short name:
hOSC
Gene namesi
Name:LSS
Synonyms:OSC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:6708. LSS.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • lipid particle Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Cataract 44 (CTRCT44)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
See also OMIM:616509
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075664581W → R in CTRCT44; loss of lanosterol synthase activity. 1 Publication1
Natural variantiVAR_075665588G → S in CTRCT44; loss of lanosterol synthase activity. 1 PublicationCorresponds to variant rs561449819dbSNPEnsembl.1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi4047.
MalaCardsiLSS.
MIMi616509. phenotype.
OpenTargetsiENSG00000160285.
PharmGKBiPA30473.

Chemistry databases

ChEMBLiCHEMBL3593.
GuidetoPHARMACOLOGYi2434.

Polymorphism and mutation databases

BioMutaiLSS.
DMDMi1352387.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000726592 – 732Lanosterol synthaseAdd BLAST731

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP48449.
MaxQBiP48449.
PaxDbiP48449.
PeptideAtlasiP48449.
PRIDEiP48449.

PTM databases

iPTMnetiP48449.
PhosphoSitePlusiP48449.
SwissPalmiP48449.

Expressioni

Gene expression databases

BgeeiENSG00000160285.
CleanExiHS_LSS.
ExpressionAtlasiP48449. baseline and differential.
GenevisibleiP48449. HS.

Organism-specific databases

HPAiCAB034116.
HPA032060.
HPA032062.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi110225. 14 interactors.
IntActiP48449. 6 interactors.
STRINGi9606.ENSP00000348762.

Chemistry databases

BindingDBiP48449.

Structurei

Secondary structure

1732
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 24Combined sources3
Beta strandi25 – 30Combined sources6
Beta strandi33 – 38Combined sources6
Beta strandi40 – 45Combined sources6
Helixi50 – 56Combined sources7
Turni61 – 63Combined sources3
Helixi73 – 85Combined sources13
Beta strandi101 – 103Combined sources3
Helixi104 – 115Combined sources12
Helixi123 – 134Combined sources12
Helixi151 – 163Combined sources13
Helixi171 – 182Combined sources12
Helixi186 – 188Combined sources3
Helixi191 – 199Combined sources9
Helixi205 – 207Combined sources3
Helixi213 – 217Combined sources5
Helixi226 – 228Combined sources3
Helixi231 – 245Combined sources15
Helixi254 – 260Combined sources7
Helixi268 – 270Combined sources3
Helixi274 – 276Combined sources3
Helixi282 – 284Combined sources3
Helixi291 – 305Combined sources15
Helixi309 – 330Combined sources22
Helixi337 – 351Combined sources15
Helixi356 – 363Combined sources8
Helixi366 – 368Combined sources3
Beta strandi369 – 372Combined sources4
Beta strandi375 – 378Combined sources4
Beta strandi380 – 382Combined sources3
Helixi385 – 398Combined sources14
Helixi401 – 403Combined sources3
Helixi405 – 407Combined sources3
Helixi408 – 421Combined sources14
Helixi430 – 433Combined sources4
Beta strandi443 – 445Combined sources3
Turni447 – 449Combined sources3
Helixi454 – 470Combined sources17
Helixi480 – 491Combined sources12
Beta strandi502 – 504Combined sources3
Helixi510 – 515Combined sources6
Helixi531 – 547Combined sources17
Helixi553 – 570Combined sources18
Beta strandi580 – 584Combined sources5
Helixi585 – 598Combined sources14
Helixi610 – 620Combined sources11
Helixi634 – 638Combined sources5
Helixi649 – 661Combined sources13
Helixi667 – 680Combined sources14
Beta strandi694 – 696Combined sources3
Turni697 – 699Combined sources3
Beta strandi700 – 702Combined sources3
Helixi707 – 722Combined sources16
Helixi727 – 729Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W6JX-ray2.20A1-732[»]
1W6KX-ray2.10A1-732[»]
ProteinModelPortaliP48449.
SMRiP48449.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP48449.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati124 – 165PFTB 1Add BLAST42
Repeati483 – 528PFTB 2Add BLAST46
Repeati560 – 600PFTB 3Add BLAST41
Repeati612 – 653PFTB 4Add BLAST42

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0497. Eukaryota.
COG1657. LUCA.
GeneTreeiENSGT00390000011570.
HOGENOMiHOG000234317.
HOVERGENiHBG005604.
InParanoidiP48449.
KOiK01852.
OMAiREWIEGM.
OrthoDBiEOG091G02LL.
PhylomeDBiP48449.
TreeFamiTF300406.

Family and domain databases

CDDicd02892. SQCY_1. 1 hit.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48449-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTEGTCLRRR GGPYKTEPAT DLGRWRLNCE RGRQTWTYLQ DERAGREQTG
60 70 80 90 100
LEAYALGLDT KNYFKDLPKA HTAFEGALNG MTFYVGLQAE DGHWTGDYGG
110 120 130 140 150
PLFLLPGLLI TCHVARIPLP AGYREEIVRY LRSVQLPDGG WGLHIEDKST
160 170 180 190 200
VFGTALNYVS LRILGVGPDD PDLVRARNIL HKKGGAVAIP SWGKFWLAVL
210 220 230 240 250
NVYSWEGLNT LFPEMWLFPD WAPAHPSTLW CHCRQVYLPM SYCYAVRLSA
260 270 280 290 300
AEDPLVQSLR QELYVEDFAS IDWLAQRNNV APDELYTPHS WLLRVVYALL
310 320 330 340 350
NLYEHHHSAH LRQRAVQKLY EHIVADDRFT KSISIGPISK TINMLVRWYV
360 370 380 390 400
DGPASTAFQE HVSRIPDYLW MGLDGMKMQG TNGSQIWDTA FAIQALLEAG
410 420 430 440 450
GHHRPEFSSC LQKAHEFLRL SQVPDNPPDY QKYYRQMRKG GFSFSTLDCG
460 470 480 490 500
WIVSDCTAEA LKAVLLLQEK CPHVTEHIPR ERLCDAVAVL LNMRNPDGGF
510 520 530 540 550
ATYETKRGGH LLELLNPSEV FGDIMIDYTY VECTSAVMQA LKYFHKRFPE
560 570 580 590 600
HRAAEIRETL TQGLEFCRRQ QRADGSWEGS WGVCFTYGTW FGLEAFACMG
610 620 630 640 650
QTYRDGTACA EVSRACDFLL SRQMADGGWG EDFESCEERR YLQSAQSQIH
660 670 680 690 700
NTCWAMMGLM AVRHPDIEAQ ERGVRCLLEK QLPNGDWPQE NIAGVFNKSC
710 720 730
AISYTSYRNI FPIWALGRFS QLYPERALAG HP
Length:732
Mass (Da):83,309
Last modified:February 1, 1996 - v1
Checksum:iE4708A5AE53585ED
GO
Isoform 2 (identifier: P48449-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: Missing.

Note: No experimental confirmation available.
Show »
Length:652
Mass (Da):74,218
Checksum:i89E4851E8F451100
GO
Isoform 3 (identifier: P48449-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     133-143: Missing.

Note: No experimental confirmation available.
Show »
Length:721
Mass (Da):82,199
Checksum:iEE5504BCAF3EEE27
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti348W → R in CAB42828 (PubMed:10598817).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024648175R → Q.Corresponds to variant rs2839158dbSNPEnsembl.1
Natural variantiVAR_052057310H → R.Corresponds to variant rs34115287dbSNPEnsembl.1
Natural variantiVAR_075664581W → R in CTRCT44; loss of lanosterol synthase activity. 1 Publication1
Natural variantiVAR_075665588G → S in CTRCT44; loss of lanosterol synthase activity. 1 PublicationCorresponds to variant rs561449819dbSNPEnsembl.1
Natural variantiVAR_052058614R → W.Corresponds to variant rs35785446dbSNPEnsembl.1
Natural variantiVAR_021522642L → V.3 PublicationsCorresponds to variant rs2254524dbSNPEnsembl.1
Natural variantiVAR_052059688P → L.Corresponds to variant rs17293705dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454071 – 80Missing in isoform 2. 1 PublicationAdd BLAST80
Alternative sequenceiVSP_046188133 – 143Missing in isoform 3. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22526 mRNA. Translation: AAC50184.1.
D63807 mRNA. Translation: BAA09875.1.
S81221 mRNA. Translation: AAB36220.1.
AJ239031
, AJ239021, AJ239022, AJ239023, AJ239024, AJ239025, AJ239026, AJ239027, AJ239028, AJ239029, AJ239030 Genomic DNA. Translation: CAB42828.1.
AK296313 mRNA. Translation: BAG59011.1.
AK226141 mRNA. No translation available.
AP001468 Genomic DNA. No translation available.
AP001469 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09299.1.
CH471079 Genomic DNA. Translation: EAX09301.1.
CH471079 Genomic DNA. Translation: EAX09302.1.
CH471079 Genomic DNA. Translation: EAX09303.1.
BC035638 mRNA. Translation: AAH35638.1.
X87809 mRNA. Translation: CAA61078.1.
CCDSiCCDS13733.1. [P48449-1]
CCDS46654.1. [P48449-3]
CCDS54489.1. [P48449-2]
PIRiJC4194.
RefSeqiNP_001001438.1. NM_001001438.2. [P48449-1]
NP_001138908.1. NM_001145436.1. [P48449-3]
NP_001138909.1. NM_001145437.1. [P48449-2]
NP_002331.3. NM_002340.5. [P48449-1]
XP_016883835.1. XM_017028346.1. [P48449-1]
XP_016883836.1. XM_017028347.1. [P48449-3]
UniGeneiHs.596543.

Genome annotation databases

EnsembliENST00000356396; ENSP00000348762; ENSG00000160285. [P48449-1]
ENST00000397728; ENSP00000380837; ENSG00000160285. [P48449-1]
ENST00000457828; ENSP00000409191; ENSG00000160285. [P48449-2]
ENST00000522411; ENSP00000429133; ENSG00000160285. [P48449-3]
GeneIDi4047.
KEGGihsa:4047.
UCSCiuc002zij.4. human. [P48449-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22526 mRNA. Translation: AAC50184.1.
D63807 mRNA. Translation: BAA09875.1.
S81221 mRNA. Translation: AAB36220.1.
AJ239031
, AJ239021, AJ239022, AJ239023, AJ239024, AJ239025, AJ239026, AJ239027, AJ239028, AJ239029, AJ239030 Genomic DNA. Translation: CAB42828.1.
AK296313 mRNA. Translation: BAG59011.1.
AK226141 mRNA. No translation available.
AP001468 Genomic DNA. No translation available.
AP001469 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09299.1.
CH471079 Genomic DNA. Translation: EAX09301.1.
CH471079 Genomic DNA. Translation: EAX09302.1.
CH471079 Genomic DNA. Translation: EAX09303.1.
BC035638 mRNA. Translation: AAH35638.1.
X87809 mRNA. Translation: CAA61078.1.
CCDSiCCDS13733.1. [P48449-1]
CCDS46654.1. [P48449-3]
CCDS54489.1. [P48449-2]
PIRiJC4194.
RefSeqiNP_001001438.1. NM_001001438.2. [P48449-1]
NP_001138908.1. NM_001145436.1. [P48449-3]
NP_001138909.1. NM_001145437.1. [P48449-2]
NP_002331.3. NM_002340.5. [P48449-1]
XP_016883835.1. XM_017028346.1. [P48449-1]
XP_016883836.1. XM_017028347.1. [P48449-3]
UniGeneiHs.596543.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W6JX-ray2.20A1-732[»]
1W6KX-ray2.10A1-732[»]
ProteinModelPortaliP48449.
SMRiP48449.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110225. 14 interactors.
IntActiP48449. 6 interactors.
STRINGi9606.ENSP00000348762.

Chemistry databases

BindingDBiP48449.
ChEMBLiCHEMBL3593.
GuidetoPHARMACOLOGYi2434.
SwissLipidsiSLP:000000646.
SLP:000001308. [P48449-1]

PTM databases

iPTMnetiP48449.
PhosphoSitePlusiP48449.
SwissPalmiP48449.

Polymorphism and mutation databases

BioMutaiLSS.
DMDMi1352387.

Proteomic databases

EPDiP48449.
MaxQBiP48449.
PaxDbiP48449.
PeptideAtlasiP48449.
PRIDEiP48449.

Protocols and materials databases

DNASUi4047.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356396; ENSP00000348762; ENSG00000160285. [P48449-1]
ENST00000397728; ENSP00000380837; ENSG00000160285. [P48449-1]
ENST00000457828; ENSP00000409191; ENSG00000160285. [P48449-2]
ENST00000522411; ENSP00000429133; ENSG00000160285. [P48449-3]
GeneIDi4047.
KEGGihsa:4047.
UCSCiuc002zij.4. human. [P48449-1]

Organism-specific databases

CTDi4047.
DisGeNETi4047.
GeneCardsiLSS.
HGNCiHGNC:6708. LSS.
HPAiCAB034116.
HPA032060.
HPA032062.
MalaCardsiLSS.
MIMi600909. gene.
616509. phenotype.
neXtProtiNX_P48449.
OpenTargetsiENSG00000160285.
PharmGKBiPA30473.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0497. Eukaryota.
COG1657. LUCA.
GeneTreeiENSGT00390000011570.
HOGENOMiHOG000234317.
HOVERGENiHBG005604.
InParanoidiP48449.
KOiK01852.
OMAiREWIEGM.
OrthoDBiEOG091G02LL.
PhylomeDBiP48449.
TreeFamiTF300406.

Enzyme and pathway databases

UniPathwayiUPA00767; UER00753.
BioCyciMetaCyc:HS08480-MONOMER.
ZFISH:HS08480-MONOMER.
BRENDAi5.4.99.7. 2681.
ReactomeiR-HSA-191273. Cholesterol biosynthesis.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

ChiTaRSiLSS. human.
EvolutionaryTraceiP48449.
GeneWikiiLanosterol_synthase.
GenomeRNAii4047.
PROiP48449.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160285.
CleanExiHS_LSS.
ExpressionAtlasiP48449. baseline and differential.
GenevisibleiP48449. HS.

Family and domain databases

CDDicd02892. SQCY_1. 1 hit.
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...

Entry informationi

Entry nameiERG7_HUMAN
AccessioniPrimary (citable) accession number: P48449
Secondary accession number(s): B4DJZ9
, D3DSN0, E9PEI9, G5E9Q9, Q8IYL6, Q9UEZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.