MSMO1_RAT
ID MSMO1_RAT Reviewed; 293 AA.
AC O35532;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Methylsterol monooxygenase 1;
DE EC=1.14.18.9 {ECO:0000305|PubMed:7228857};
DE AltName: Full=C-4 methylsterol oxidase;
DE AltName: Full=Neuropep 1;
DE AltName: Full=RANP-1;
DE AltName: Full=Sterol-C4-methyl oxidase;
GN Name=Msmo1; Synonyms=Sc4mol;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=9284352; DOI=10.1016/s0306-4522(97)00112-7;
RA Uwabe K., Gahara Y., Yamada H., Miyake T., Kitamura T.;
RT "Identification and characterization of a novel gene (neurorep 1) expressed
RT in nerve cells and up-regulated after axotomy.";
RL Neuroscience 80:501-509(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
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).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=4394229; DOI=10.1016/s0021-9258(18)62765-6;
RA Miller W.L., Gaylor J.L.;
RT "Investigation of the component reactions of oxidative sterol
RT demethylation. Oxidation of a 4,4-dimethyl sterol to a 4 beta-methyl-4
RT alpha-carboxylic acid during cholesterol biosynthesis.";
RL J. Biol. Chem. 245:5375-5381(1970).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=7228857; DOI=10.1016/s0021-9258(19)69327-0;
RA Fukushima H., Grinstead G.F., Gaylor J.L.;
RT "Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-
RT dependence of 4-methyl sterol oxidase.";
RL J. Biol. Chem. 256:4822-4826(1981).
CC -!- FUNCTION: Catalyzes the three-step monooxygenation required for the
CC demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be
CC subsequently metabolized to cholesterol. {ECO:0000305|PubMed:4394229,
CC ECO:0000305|PubMed:7228857}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-4beta-methyl-5alpha-
CC cholest-7-ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:55220, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16455, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:58387; EC=1.14.18.9;
CC Evidence={ECO:0000305|PubMed:7228857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55221;
CC Evidence={ECO:0000305|PubMed:7228857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4beta-methylzymosterol-4alpha-
CC carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:55244, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:64925; Evidence={ECO:0000250|UniProtKB:Q15800};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55245;
CC Evidence={ECO:0000250|UniProtKB:Q15800};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 5 H(+) +
CC 3 O2 = 4alpha-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:47056, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:1949, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:143575; Evidence={ECO:0000250|UniProtKB:Q15800};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47057;
CC Evidence={ECO:0000250|UniProtKB:Q15800};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-5alpha-cholest-7-en-
CC 3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O; Xref=Rhea:RHEA:62768,
CC Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18378,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:145943;
CC Evidence={ECO:0000305|PubMed:7228857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62769;
CC Evidence={ECO:0000305|PubMed:7228857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-4beta-methyl-5alpha-
CC cholest-8-en-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:62776, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:87044,
CC ChEBI:CHEBI:87047; Evidence={ECO:0000250|UniProtKB:Q15800};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62777;
CC Evidence={ECO:0000250|UniProtKB:Q15800};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-5alpha-cholest-8-
CC ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:62780, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:87051,
CC ChEBI:CHEBI:87055; Evidence={ECO:0000250|UniProtKB:Q15800};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62781;
CC Evidence={ECO:0000250|UniProtKB:Q15800};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q15800};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 3/6. {ECO:0000305}.
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000305|PubMed:4394229, ECO:0000305|PubMed:7228857}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; D50559; BAA23329.1; -; mRNA.
DR EMBL; BC063155; AAH63155.1; -; mRNA.
DR RefSeq; NP_543162.1; NM_080886.1.
DR AlphaFoldDB; O35532; -.
DR IntAct; O35532; 4.
DR STRING; 10116.ENSRNOP00000043782; -.
DR jPOST; O35532; -.
DR PaxDb; O35532; -.
DR PRIDE; O35532; -.
DR Ensembl; ENSRNOT00000044171; ENSRNOP00000043782; ENSRNOG00000032297.
DR GeneID; 140910; -.
DR KEGG; rno:140910; -.
DR UCSC; RGD:620281; rat.
DR CTD; 6307; -.
DR RGD; 620281; Msmo1.
DR eggNOG; KOG0873; Eukaryota.
DR GeneTree; ENSGT00940000158012; -.
DR HOGENOM; CLU_047036_5_2_1; -.
DR InParanoid; O35532; -.
DR OMA; IVHEFIY; -.
DR OrthoDB; 1493916at2759; -.
DR PhylomeDB; O35532; -.
DR TreeFam; TF354294; -.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR SABIO-RK; O35532; -.
DR UniPathway; UPA00063; -.
DR UniPathway; UPA00770; UER00756.
DR PRO; PR:O35532; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000032297; Expressed in ovary and 20 other tissues.
DR Genevisible; O35532; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000254; F:C-4 methylsterol oxidase activity; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 1: Evidence at protein level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Iron; Lipid biosynthesis; Lipid metabolism; Membrane; NAD; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..293
FT /note="Methylsterol monooxygenase 1"
FT /id="PRO_0000117036"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 144..274
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 157..161
FT /note="Histidine box-1"
FT MOTIF 170..174
FT /note="Histidine box-2"
FT MOTIF 249..255
FT /note="Histidine box-3"
SQ SEQUENCE 293 AA; 34964 MW; FEE8C22FDC5F38D7 CRC64;
MAMNKSVGLF SSASLAVDYV DSLLPENPLQ EPFKNAWVYM LDNYTKFQIA TWGSLIVHET
IYFLFSLPGF LFQFIPFMRK YKIQKDKPET FEGQWKCLKG ILFNHFFIQL PLICGTYYFT
EFFNIPYDWE RMPRWYFTLA RCLGCAVIED TWHYFLHRLL HHKRIYKYIH KVHHEFQAPF
GIEAEYAHPL ETLILGTGFF IGIVLLCDHV ILLWAWVTMR LLETIDVHSG YDIPLNPLNY
IPFYTGARHH DFHHMNFIGN YASTFTWWDR IFGTDVQYHA YTEKMKKLGK KSE
