P48449 (ERG7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	LSS
Synonyms:	OSC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	732 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.6
Pathway	Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 3/3.
Subunit structure	Monomer. Ref.6
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein Ref.6 Ref.9.
Sequence similarities	Belongs to the terpene cyclase/mutase family. Contains 4 PFTB repeats.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Molecular function	Isomerase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular function	lanosterol synthase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 732

731

Lanosterol synthase

PRO_0000072659

Regions

Repeat

124 – 165

42

PFTB 1

Repeat

483 – 528

46

PFTB 2

Repeat

560 – 600

41

PFTB 3

Repeat

612 – 653

42

PFTB 4

Sites

Active site

232

1

Proton acceptor

Active site

455

1

Proton donor Probable

Natural variations

Natural variant

175

1

R → Q.
Corresponds to variant rs2839158 [ dbSNP | Ensembl ].

VAR_024648

Natural variant

310

1

H → R.
Corresponds to variant rs34115287 [ dbSNP | Ensembl ].

VAR_052057

Natural variant

614

1

R → W.
Corresponds to variant rs35785446 [ dbSNP | Ensembl ].

VAR_052058

Natural variant

642

1

L → V. Ref.5
Corresponds to variant rs2254524 [ dbSNP | Ensembl ].

VAR_021522

Natural variant

688

1

P → L.
Corresponds to variant rs17293705 [ dbSNP | Ensembl ].

VAR_052059

Experimental info

Sequence conflict

348

1

W → R in CAB42828. Ref.3

Secondary structure

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732

Helix Strand Turn

Details...

Helix

22 – 24

3

Beta strand

25 – 30

6

Beta strand

33 – 38

6

Beta strand

40 – 45

6

Helix

50 – 56

7

Turn

61 – 63

3

Helix

73 – 85

13

Beta strand

101 – 103

3

Helix

104 – 114

11

Helix

123 – 134

12

Helix

151 – 163

13

Helix

171 – 182

12

Helix

186 – 188

3

Helix

191 – 199

9

Helix

205 – 207

3

Helix

213 – 217

5

Helix

226 – 228

3

Helix

231 – 245

15

Helix

254 – 262

9

Helix

268 – 270

3

Helix

273 – 276

4

Helix

282 – 284

3

Helix

291 – 305

15

Helix

309 – 330

22

Helix

337 – 351

15

Helix

356 – 363

8

Helix

366 – 368

3

Beta strand

369 – 372

4

Beta strand

375 – 378

4

Beta strand

380 – 382

3

Helix

385 – 398

14

Helix

401 – 403

3

Helix

405 – 407

3

Helix

408 – 421

14

Helix

430 – 433

4

Beta strand

443 – 445

3

Turn

447 – 449

3

Helix

454 – 470

17

Helix

480 – 491

12

Beta strand

502 – 504

3

Helix

510 – 515

6

Helix

531 – 547

17

Helix

553 – 570

18

Beta strand

580 – 584

5

Helix

585 – 598

14

Helix

610 – 620

11

Helix

634 – 638

5

Helix

649 – 661

13

Helix

667 – 680

14

Beta strand

694 – 696

3

Turn

697 – 699

3

Beta strand

700 – 702

3

Helix

707 – 722

16

Helix

727 – 729

3

Sequences

	Sequence		Length	Mass (Da)
	P48449 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: E4708A5AE53585ED	FASTA	732	83,309
	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

References

	« Hide 'large scale' referencesShow '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: 7639730] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 8593458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[3]	"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: 10598817] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	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. , 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].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-642. Tissue: Eye.
[6]	"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: 14766201] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-5, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION.
[7]	"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: 8655142] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-630. Tissue: Fetal brain.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"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: 15525992] [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 , AJ239021, AJ239022, AJ239023, AJ239024, AJ239025, AJ239026, AJ239027, AJ239028, AJ239029, AJ239030 Genomic DNA. Translation: CAB42828.1.
CH471079 Genomic DNA. Translation: EAX09299.1.
CH471079 Genomic DNA. Translation: EAX09301.1.
CH471079 Genomic DNA. Translation: EAX09302.1.
BC035638 mRNA. Translation: AAH35638.1.
X87809 mRNA. Translation: CAA61078.1.

IPI

IPI00009747.

PIR

JC4194.

RefSeq

NP_001001438.1. NM_001001438.2.
NP_001138908.1. NM_001145436.1.
NP_001138909.1. NM_001145437.1.
NP_002331.3. NM_002340.5.

UniGene

Hs.596543.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W6J	X-ray	2.20	A	1-732	[»]
1W6K	X-ray	2.10	A	1-732	[»]

ProteinModelPortal

P48449.

SMR

P48449. Positions 6-732.

ModBase

Search...

Protein-protein interaction databases

IntAct

P48449. 1 interaction.

STRING

P48449.

PTM databases

PhosphoSite

P48449.

Polymorphism databases

DMDM

1352387.

Proteomic databases

PeptideAtlas

P48449.

PRIDE

P48449.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356396; ENSP00000348762; ENSG00000160285.
ENST00000397728; ENSP00000380837; ENSG00000160285.

GeneID

4047.

KEGG

hsa:4047.

UCSC

uc002zij.1. human.

Organism-specific databases

CTD

4047.

GeneCards

GC21M047608.

H-InvDB

HIX0016191.

HGNC

HGNC:6708. LSS.

HPA

HPA032060.

MIM

600909. gene.

neXtProt

NX_P48449.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06314.

GeneTree

ENSGT00390000011570.

HOGENOM

HBG750669.

HOVERGEN

HBG005604.

InParanoid

P48449.

OMA

YLPMAYC.

OrthoDB

EOG4SQWW4.

PhylomeDB

P48449.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000160285-MONOMER.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P48449.

Bgee

P48449.

CleanEx

HS_LSS.

Genevestigator

P48449.

GermOnline

ENSG00000160285. Homo sapiens.

Family and domain databases

InterPro

IPR001330. Prenyltrans.
IPR018333. Squalene_cyclase.
IPR002365. Terpene_synthase_CS.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]

KO

K01852.

Pfam

PF00432. Prenyltrans. 3 hits.
[Graphical view]

SUPFAM

SSF48239. Terp_cyc_toroid. 2 hits.

TIGRFAMs

TIGR01787. Squalene_cyclas. 1 hit.

PROSITE

PS01074. TERPENE_SYNTHASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

15850.

SOURCE

Search...

Entry information

Entry name

ERG7_HUMAN

Accession

Primary (citable) accession number: P48449
Secondary accession number(s): D3DSN0, Q8IYL6, Q9UEZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	January 25, 2012
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.