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P48449 (ERG7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:LSS
Synonyms:OSC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length732 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Ref.1

Catalytic activity

(3S)-2,3-epoxy-2,3-dihydrosqualene = lanosterol. Ref.1 Ref.9

Pathway

Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 3/3.

Subunit structure

Monomer. Ref.9

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein Ref.9 Ref.13.

Sequence similarities

Belongs to the terpene cyclase/mutase family.

Contains 4 PFTB repeats.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P48449-1)

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.
Isoform 2 (identifier: P48449-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P48449-3)

The sequence of this isoform differs from the canonical sequence as follows:
     133-143: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9 Ref.12
Chain2 – 732731Lanosterol synthase
PRO_0000072659

Regions

Repeat124 – 16542PFTB 1
Repeat483 – 52846PFTB 2
Repeat560 – 60041PFTB 3
Repeat612 – 65342PFTB 4

Sites

Active site2321Proton acceptor
Active site4551Proton donor Probable

Amino acid modifications

Modified residue21N-acetylthreonine Ref.12

Natural variations

Alternative sequence1 – 8080Missing in isoform 2.
VSP_045407
Alternative sequence133 – 14311Missing in isoform 3.
VSP_046188
Natural variant1751R → Q.
Corresponds to variant rs2839158 [ dbSNP | Ensembl ].
VAR_024648
Natural variant3101H → R.
Corresponds to variant rs34115287 [ dbSNP | Ensembl ].
VAR_052057
Natural variant6141R → W.
Corresponds to variant rs35785446 [ dbSNP | Ensembl ].
VAR_052058
Natural variant6421L → V. Ref.3 Ref.5 Ref.8
Corresponds to variant rs2254524 [ dbSNP | Ensembl ].
VAR_021522
Natural variant6881P → L.
Corresponds to variant rs17293705 [ dbSNP | Ensembl ].
VAR_052059

Experimental info

Sequence conflict3481W → R in CAB42828. Ref.4

Secondary structure

...................................................................................................... 732
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: E4708A5AE53585ED

FASTA73283,309
        10         20         30         40         50         60 
MTEGTCLRRR GGPYKTEPAT DLGRWRLNCE RGRQTWTYLQ DERAGREQTG LEAYALGLDT 

        70         80         90        100        110        120 
KNYFKDLPKA HTAFEGALNG MTFYVGLQAE DGHWTGDYGG PLFLLPGLLI TCHVARIPLP 

       130        140        150        160        170        180 
AGYREEIVRY LRSVQLPDGG WGLHIEDKST VFGTALNYVS LRILGVGPDD PDLVRARNIL 

       190        200        210        220        230        240 
HKKGGAVAIP SWGKFWLAVL NVYSWEGLNT LFPEMWLFPD WAPAHPSTLW CHCRQVYLPM 

       250        260        270        280        290        300 
SYCYAVRLSA AEDPLVQSLR QELYVEDFAS IDWLAQRNNV APDELYTPHS WLLRVVYALL 

       310        320        330        340        350        360 
NLYEHHHSAH LRQRAVQKLY EHIVADDRFT KSISIGPISK TINMLVRWYV DGPASTAFQE 

       370        380        390        400        410        420 
HVSRIPDYLW MGLDGMKMQG TNGSQIWDTA FAIQALLEAG GHHRPEFSSC LQKAHEFLRL 

       430        440        450        460        470        480 
SQVPDNPPDY QKYYRQMRKG GFSFSTLDCG WIVSDCTAEA LKAVLLLQEK CPHVTEHIPR 

       490        500        510        520        530        540 
ERLCDAVAVL LNMRNPDGGF ATYETKRGGH LLELLNPSEV FGDIMIDYTY VECTSAVMQA 

       550        560        570        580        590        600 
LKYFHKRFPE HRAAEIRETL TQGLEFCRRQ QRADGSWEGS WGVCFTYGTW FGLEAFACMG 

       610        620        630        640        650        660 
QTYRDGTACA EVSRACDFLL SRQMADGGWG EDFESCEERR YLQSAQSQIH NTCWAMMGLM 

       670        680        690        700        710        720 
AVRHPDIEAQ ERGVRCLLEK QLPNGDWPQE NIAGVFNKSC AISYTSYRNI FPIWALGRFS 

       730 
QLYPERALAG HP 

« Hide

Isoform 2 [UniParc].

Checksum: 89E4851E8F451100
Show »

FASTA65274,218
Isoform 3 [UniParc].

Checksum: EE5504BCAF3EEE27
Show »

FASTA72182,199

References

« Hide 'large scale' references
[1]"Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library."
Baker C.H., Matsuda S.P.T., Liu D.R., Corey E.J.
Biochem. Biophys. Res. Commun. 213:154-160(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY.
Tissue: Liver.
[2]"Molecular cloning of cDNA encoding human lanosterol synthase."
Sung C.K., Shibuya M., Sankawa U., Ebizuka Y.
Biol. Pharm. Bull. 18:1459-1461(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal liver.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT VAL-642.
Tissue: Thalamus.
[4]"Structure of the human lanosterol synthase gene and its analysis as a candidate for holoprosencephaly."
Roessler E., Mittaz L., Du Y., Scott H.S., Chang J., Rossier C., Guipponi M., Matsuda S.P., Muenke M., Antonarakis S.E.
Hum. Genet. 105:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT VAL-642.
Tissue: Brain.
[6]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-642.
Tissue: Eye.
[9]"The monotopic membrane protein human oxidosqualene cyclase is active as monomer."
Ruf A., Muller F., D'Arcy B., Stihle M., Kusznir E., Handschin C., Morand O.H., Thoma R.
Biochem. Biophys. Res. Commun. 315:247-254(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-5, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION.
[10]"The human lanosterol synthase gene maps to chromosome 21q22.3."
Young M., Chen H., Lalioti M.D., Antonarakis S.E.
Hum. Genet. 97:620-624(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-630 (ISOFORM 1).
Tissue: Fetal brain.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[13]"Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase."
Thoma R., Schulz-Gasch T., D'Arcy B., Benz J., Aebi J., Dehmlow H., Hennig M., Stihle M., Ruf A.
Nature 432:118-122(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH LANOSTEROL AND RO 48-807, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U22526 mRNA. Translation: AAC50184.1.
D63807 mRNA. Translation: BAA09875.1.
S81221 mRNA. Translation: AAB36220.1.
AJ239031 expand/collapse EMBL AC list , 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.
PIRJC4194.
RefSeqNP_001001438.1. NM_001001438.2.
NP_001138908.1. NM_001145436.1.
NP_001138909.1. NM_001145437.1.
NP_002331.3. NM_002340.5.
UniGeneHs.596543.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1W6JX-ray2.20A1-732[»]
1W6KX-ray2.10A1-732[»]
ProteinModelPortalP48449.
SMRP48449. Positions 6-732.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110225. 4 interactions.
IntActP48449. 1 interaction.
STRING9606.ENSP00000348762.

Chemistry

BindingDBP48449.
ChEMBLCHEMBL3593.
GuidetoPHARMACOLOGY2434.

PTM databases

PhosphoSiteP48449.

Polymorphism databases

DMDM1352387.

Proteomic databases

PaxDbP48449.
PeptideAtlasP48449.
PRIDEP48449.

Protocols and materials databases

DNASU4047.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356396; ENSP00000348762; ENSG00000160285. [P48449-1]
ENST00000397728; ENSP00000380837; ENSG00000160285. [P48449-1]
ENST00000457828; ENSP00000409191; ENSG00000160285. [P48449-2]
ENST00000522411; ENSP00000429133; ENSG00000160285. [P48449-3]
GeneID4047.
KEGGhsa:4047.
UCSCuc002zij.3. human. [P48449-1]

Organism-specific databases

CTD4047.
GeneCardsGC21M047608.
HGNCHGNC:6708. LSS.
HPACAB034116.
HPA032060.
HPA032062.
MIM600909. gene.
neXtProtNX_P48449.
PharmGKBPA30473.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1657.
HOGENOMHOG000234317.
HOVERGENHBG005604.
InParanoidP48449.
KOK01852.
OMATARCVSM.
OrthoDBEOG70W3CN.
PhylomeDBP48449.
TreeFamTF300406.

Enzyme and pathway databases

BioCycMetaCyc:HS08480-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00767; UER00753.

Gene expression databases

ArrayExpressP48449.
BgeeP48449.
CleanExHS_LSS.
GenevestigatorP48449.

Family and domain databases

Gene3D1.50.10.20. 2 hits.
InterProIPR001330. Prenyltrans.
IPR018333. Squalene_cyclase.
IPR002365. Terpene_synthase_CS.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamPF00432. Prenyltrans. 3 hits.
[Graphical view]
SUPFAMSSF48239. SSF48239. 2 hits.
TIGRFAMsTIGR01787. squalene_cyclas. 1 hit.
PROSITEPS01074. TERPENE_SYNTHASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLSS. human.
EvolutionaryTraceP48449.
GeneWikiLanosterol_synthase.
GenomeRNAi4047.
NextBio15850.
PROP48449.
SOURCESearch...

Entry information

Entry nameERG7_HUMAN
AccessionPrimary (citable) accession number: P48449
Secondary accession number(s): B4DJZ9 expand/collapse secondary AC list , D3DSN0, E9PEI9, G5E9Q9, Q8IYL6, Q9UEZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM