ERG1_MOUSE
ID ERG1_MOUSE Reviewed; 572 AA.
AC P52019;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Squalene monooxygenase;
DE EC=1.14.14.17 {ECO:0000250|UniProtKB:P52020};
DE AltName: Full=Squalene epoxidase {ECO:0000303|PubMed:7873613};
DE Short=SE;
GN Name=Sqle; Synonyms=Erg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=7873613; DOI=10.1016/0167-4781(94)00245-x;
RA Kosuga K., Hata S., Osumi T., Sakakibara J., Ono T.;
RT "Nucleotide sequence of a cDNA for mouse squalene epoxidase.";
RL Biochim. Biophys. Acta 1260:345-348(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NMRI; TISSUE=Brain, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-
CC 2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in
CC steroid biosynthesis. {ECO:0000250|UniProtKB:P52020}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + squalene = (S)-
CC 2,3-epoxysqualene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:25282, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:15441, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.17;
CC Evidence={ECO:0000250|UniProtKB:P52020};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q14534};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 2/3. {ECO:0000250|UniProtKB:Q14534}.
CC -!- SUBUNIT: Interacts (via N-terminal domain) with MARCHF6. Interacts with
CC SMIM22; this interaction modulates lipid droplet formation.
CC {ECO:0000250|UniProtKB:Q14534}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P52020}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14534}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q14534}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14534}.
CC -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:7873613}.
CC -!- DOMAIN: The C-terminal hydrophobic region contains two helices that
CC mediate interaction with membranes. Contrary to predictions, this
CC region does not contain transmembrane helices.
CC {ECO:0000250|UniProtKB:Q14534}.
CC -!- DOMAIN: The N-terminal region mediates interaction with MARCHF6,
CC leading to SQLE ubiquitination and proteasomal degradation when
CC cholosterol levels are high. The first part of the N-terminal region
CC contains a hydrophobic region that inserts into the membrane; contrary
CC to predictions, there are no transmembrane helices. The second part
CC contains a region that can form an amphipathic region that associates
CC with membranes. This region is ejected from the membrane by high
CC cholesterol levels and becomes disordered in an aqueous environment.
CC This is critical for cholesterol-dependent proteasomal degradation.
CC Additional parts of the N-terminal region are predicted to be
CC disordered and contribute to flagging the protein for proteasomal
CC degradation already under basal conditions.
CC {ECO:0000250|UniProtKB:Q14534}.
CC -!- PTM: Ubiquitinated by MARCHF6 in response to high cholesterol levels in
CC intracellular membranes, leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q14534}.
CC -!- SIMILARITY: Belongs to the squalene monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; D42048; BAA07649.1; -; mRNA.
DR EMBL; BC042781; AAH42781.1; -; mRNA.
DR EMBL; BC056361; AAH56361.1; -; mRNA.
DR CCDS; CCDS27497.1; -.
DR PIR; S52113; S52113.
DR RefSeq; NP_033296.1; NM_009270.3.
DR AlphaFoldDB; P52019; -.
DR SMR; P52019; -.
DR STRING; 10090.ENSMUSP00000022977; -.
DR iPTMnet; P52019; -.
DR PhosphoSitePlus; P52019; -.
DR SwissPalm; P52019; -.
DR EPD; P52019; -.
DR PaxDb; P52019; -.
DR PeptideAtlas; P52019; -.
DR PRIDE; P52019; -.
DR ProteomicsDB; 275941; -.
DR Antibodypedia; 27121; 166 antibodies from 27 providers.
DR DNASU; 20775; -.
DR Ensembl; ENSMUST00000022977; ENSMUSP00000022977; ENSMUSG00000022351.
DR GeneID; 20775; -.
DR KEGG; mmu:20775; -.
DR UCSC; uc007vxq.1; mouse.
DR CTD; 6713; -.
DR MGI; MGI:109296; Sqle.
DR VEuPathDB; HostDB:ENSMUSG00000022351; -.
DR eggNOG; KOG1298; Eukaryota.
DR GeneTree; ENSGT00390000011759; -.
DR InParanoid; P52019; -.
DR OMA; KSKFWGL; -.
DR OrthoDB; 583514at2759; -.
DR PhylomeDB; P52019; -.
DR TreeFam; TF331056; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00767; UER00752.
DR BioGRID-ORCS; 20775; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Sqle; mouse.
DR PRO; PR:P52019; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P52019; protein.
DR Bgee; ENSMUSG00000022351; Expressed in undifferentiated genital tubercle and 254 other tissues.
DR ExpressionAtlas; P52019; baseline and differential.
DR Genevisible; P52019; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0004506; F:squalene monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0006725; P:cellular aromatic compound metabolic process; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:MGI.
DR GO; GO:0140042; P:lipid droplet formation; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0016126; P:sterol biosynthetic process; ISS:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR013698; Squalene_epoxidase.
DR InterPro; IPR040125; Squalene_monox.
DR PANTHER; PTHR10835; PTHR10835; 1.
DR Pfam; PF08491; SE; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid metabolism; Membrane;
KW Microsome; Oxidoreductase; Reference proteome; Ubl conjugation.
FT CHAIN 1..572
FT /note="Squalene monooxygenase"
FT /id="PRO_0000209839"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT INTRAMEM 20..40
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT TOPO_DOM 41..572
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT REGION 1..98
FT /note="Interaction with MARCHF6"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT REGION 61..72
FT /note="Required for degradation in response to high
FT membrane cholesterol levels"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT REGION 116..572
FT /note="Sufficient for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT REGION 514..572
FT /note="Hydrophobic; mediates interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 131..132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 151..152
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 159
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 232
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 248
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 406
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 419
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT SITE 193
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
SQ SEQUENCE 572 AA; 63770 MW; 5C30D80A204664D4 CRC64;
MWTFLGIATF TYFYKKCGDV TLANKELLLC VLVFLSLGLV LSYRCRHRHG GLLGRHQSGA
QFAAFSDILS ALPLIGFFWA KSPESEKKEQ LESKKCRKEI GLSETTLTGA ATSVSTSFVT
DPEVIIVGSG VLGSALAAVL SRDGRKVTVI ERDLKEPDRI VGELLQPGGY RVLQELGLGD
TVEGLNAHHI HGYIVHDYES RSEVQIPYPL SETNQVQSGI AFHHGRFIMS LRKAAMAEPN
VKFIEGVVLQ LLEEDDAVIG VQYKDKETGD TKELHAPLTV VADGLFSKFR KSLISSKVSV
SSHFVGFLMK DAPQFKPNFA ELVLVNPSPV LIYQISSSET RVLVDIRGEL PRNLREYMAE
QIYPQLPEHL KESFLEASQN GRLRTMPASF LPPSSVNKRG VLILGDAYNL RHPLTGGGMT
VALKDIKLWR QLLKDIPDLY DDAAIFQAKK SFFWSRKRTH SFVVNVLAQA LYELFSATDD
SLHQLRKACF LYFKLGGECV TGPVGLLSIL SPHPLVLIRH FFSVAIYATY FCFKSEPWAT
KPRALFSSGA VLYKACSILF PLIYSEMKYL VH
