ID   ERG25_YEAST             Reviewed;         309 AA.
AC   P53045; Q45U26;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   16-JUN-2009, entry version 77.
DE   RecName: Full=C-4 methylsterol oxidase;
DE            EC=1.14.13.72;
DE   AltName: Full=Methylsterol monooxygenase;
GN   Name=ERG25; Synonyms=FET6; OrderedLocusNames=YGR060W;
OS   Saccharomyces cerevisiae (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina;
OC   Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=4932;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=96133902; PubMed=8552601; DOI=10.1073/pnas.93.1.186;
RA   Bard M., Bruner D.A., Pierson C.A., Lees N.D., Biermann B., Frye L.,
RA   Koegel C., Barbuch R.;
RT   "Cloning and characterization of ERG25, the Saccharomyces cerevisiae
RT   gene encoding C-4 sterol methyl oxidase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:186-190(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, COFACTOR, AND SUBCELLULAR
RP   LOCATION.
RX   MEDLINE=96279274; PubMed=8663358; DOI=10.1074/jbc.271.28.16927;
RA   Li L., Kaplan J.;
RT   "Characterization of yeast methyl sterol oxidase (ERG25) and
RT   identification of a human homologue.";
RL   J. Biol. Chem. 271:16927-16933(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=SK1;
RX   PubMed=16273108; DOI=10.1038/ng1674;
RA   Deutschbauer A.M., Davis R.W.;
RT   "Quantitative trait loci mapped to single-nucleotide resolution in
RT   yeast.";
RL   Nat. Genet. 37:1333-1340(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   MEDLINE=97313265; PubMed=9169869;
RA   Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M.,
RA   Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J.,
RA   Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E.,
RA   Clemente M.L., Coblenz A., Coglievina M., Coissac E., Defoor E.,
RA   Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B.,
RA   Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L.,
RA   Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M.,
RA   Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M.,
RA   Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B.,
RA   Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W.,
RA   Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A.,
RA   Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA   Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S.,
RA   Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L.,
RA   Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S.,
RA   Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J.,
RA   Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M.,
RA   Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B.,
RA   Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J.,
RA   Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M.,
RA   van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M.,
RA   Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H.,
RA   Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M.,
RA   Zollner A., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL   Nature 387:81-84(1997).
RN   [5]
RP   SUBUNIT, INTERACTION WITH ERG27 AND ERG28, AND SUBCELLULAR LOCATION.
RX   PubMed=12119386; DOI=10.1073/pnas.112202799;
RA   Mo C., Valachovic M., Randall S.K., Nickels J.T., Bard M.;
RT   "Protein-protein interactions among C-4 demethylation enzymes involved
RT   in yeast sterol biosynthesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:9739-9744(2002).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   MEDLINE=22923965; PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A.,
RA   Dephoure N., O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-96, AND MASS
RP   SPECTROMETRY.
RX   PubMed=14557538; DOI=10.1073/pnas.2135500100;
RA   Hitchcock A.L., Auld K., Gygi S.P., Silver P.A.;
RT   "A subset of membrane-associated proteins is ubiquitinated in response
RT   to mutations in the endoplasmic reticulum degradation machinery.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003).
RN   [8]
RP   INTERACTION WITH ERG28.
RX   PubMed=15995173; DOI=10.1194/jlr.M500153-JLR200;
RA   Mo C., Bard M.;
RT   "Erg28p is a key protein in the yeast sterol biosynthetic enzyme
RT   complex.";
RL   J. Lipid Res. 46:1991-1998(2005).
RN   [9]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15716577; DOI=10.1074/mcp.M400123-MCP200;
RA   Natter K., Leitner P., Faschinger A., Wolinski H., McCraith S.,
RA   Fields S., Kohlwein S.D.;
RT   "The spatial organization of lipid synthesis in the yeast
RT   Saccharomyces cerevisiae derived from large scale green fluorescent
RT   protein tagging and high resolution microscopy.";
RL   Mol. Cell. Proteomics 4:662-672(2005).
CC   -!- FUNCTION: Catalyzes the first step in the removal of the two C-4
CC       methyl groups of 4,4-dimethylzymosterol.
CC   -!- CATALYTIC ACTIVITY: 4,4-dimethyl-5-alpha-cholest-7-en-3-beta-ol +
CC       NAD(P)H + O(2) = 4-beta-hydroxymethyl-4-alpha-methyl-5-alpha-
CC       cholest-7-en-3-beta-ol + NAD(P)(+) + H(2)O.
CC   -!- CATALYTIC ACTIVITY: 4-beta-hydroxymethyl-4-alpha-methyl-5-alpha-
CC       cholest-7-en-3-beta-ol + NAD(P)H + O(2) = 3-beta-hydroxy-4-beta-
CC       methyl-5-alpha-cholest-7-ene-4-alpha-carbaldehyde + NAD(P)(+) + 2
CC       H(2)O.
CC   -!- CATALYTIC ACTIVITY: 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-
CC       7-ene-4-alpha-carbaldehyde + NAD(P)H + O(2) = 3-beta-hydroxy-4-
CC       beta-methyl-5-alpha-cholest-7-ene-4-alpha-carboxylate + NAD(P)(+)
CC       + H(2)O.
CC   -!- COFACTOR: Iron.
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol
CC       from lanosterol: step 3/6.
CC   -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28. ERG28
CC       acts as a scaffold to tether ERG27 and other 4,4-demethylation-
CC       related enzymes, forming a demethylation enzyme complex, in the
CC       endoplasmic reticulum. Interacts with ERG27 and ERG28.
CC   -!- INTERACTION:
CC       P36039:-; NbExp=1; IntAct=EBI-6506, EBI-27005;
CC       P38142:-; NbExp=1; IntAct=EBI-6506, EBI-21079;
CC       P38845:-; NbExp=1; IntAct=EBI-6506, EBI-24770;
CC       P40207:-; NbExp=1; IntAct=EBI-6506, EBI-27272;
CC       P47133:-; NbExp=1; IntAct=EBI-6506, EBI-25568;
CC       Q12164:-; NbExp=1; IntAct=EBI-6506, EBI-30000;
CC       P25376:AGP1; NbExp=1; IntAct=EBI-6506, EBI-2357;
CC       P40350:ALG5; NbExp=1; IntAct=EBI-6506, EBI-2470;
CC       P04817:CAN1; NbExp=1; IntAct=EBI-6506, EBI-3993;
CC       P08456:CHO1; NbExp=1; IntAct=EBI-6506, EBI-14055;
CC       P39540:ELO1; NbExp=1; IntAct=EBI-6506, EBI-2049096;
CC       P32476:ERG1; NbExp=1; IntAct=EBI-6506, EBI-6545;
CC       P10614:ERG11; NbExp=1; IntAct=EBI-6506, EBI-5127;
CC       Q12452:ERG27; NbExp=1; IntAct=EBI-6506, EBI-38132;
CC       P40030:ERG28; NbExp=1; IntAct=EBI-6506, EBI-22518;
CC       Q05359:ERP1; NbExp=1; IntAct=EBI-6506, EBI-6581;
CC       P39704:ERP2; NbExp=1; IntAct=EBI-6506, EBI-6587;
CC       P54837:ERV25; NbExp=1; IntAct=EBI-6506, EBI-6642;
CC       P19145:GAP1; NbExp=1; IntAct=EBI-6506, EBI-7314;
CC       P40499:ICE2; NbExp=1; IntAct=EBI-6506, EBI-25109;
CC       Q06144:ORM2; NbExp=1; IntAct=EBI-6506, EBI-34916;
CC       P41543:OST1; NbExp=1; IntAct=EBI-6506, EBI-12651;
CC       P25297:PHO84; NbExp=1; IntAct=EBI-6506, EBI-13320;
CC       P46956:PHO86; NbExp=1; IntAct=EBI-6506, EBI-13337;
CC       P38264:PHO88; NbExp=1; IntAct=EBI-6506, EBI-13350;
CC       P40857:PHS1; NbExp=1; IntAct=EBI-6506, EBI-26003;
CC       P40975:PMP2; NbExp=1; IntAct=EBI-6506, EBI-2043041;
CC       P87284:PMP3; NbExp=1; IntAct=EBI-6506, EBI-13555;
CC       P13586:PMR1; NbExp=1; IntAct=EBI-6506, EBI-3091;
CC       P26570:PPZ1; NbExp=1; IntAct=EBI-6506, EBI-13807;
CC       Q12270:RBD2; NbExp=1; IntAct=EBI-6506, EBI-31471;
CC       Q04947:RTN1; NbExp=1; IntAct=EBI-6506, EBI-38020;
CC       P32368:SAC1; NbExp=1; IntAct=EBI-6506, EBI-16210;
CC       P14906:SEC63; NbExp=1; IntAct=EBI-6506, EBI-16636;
CC       Q04969:SPC2; NbExp=1; IntAct=EBI-6506, EBI-27827;
CC       P39986:SPF1; NbExp=1; IntAct=EBI-6506, EBI-3128;
CC       P38353:SSH1; NbExp=1; IntAct=EBI-6506, EBI-18175;
CC       P25037:UBP1; NbExp=1; IntAct=EBI-6506, EBI-19819;
CC       P40107:VRG4; NbExp=1; IntAct=EBI-6506, EBI-7764;
CC       Q3E7B0:YER053C-A; NbExp=1; IntAct=EBI-6506, EBI-2047907;
CC       P35723:YET1; NbExp=1; IntAct=EBI-6506, EBI-26730;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC       membrane protein (Probable).
CC   -!- DOMAIN: The histidine box domains may contain the active site
CC       and/or be involved in metal ion binding.
CC   -!- MISCELLANEOUS: Present with 77100 molecules/cell in log phase SD
CC       medium.
CC   -!- SIMILARITY: Belongs to the sterol desaturase family.
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DR   EMBL; U31885; AAC49139.1; -; Genomic_DNA.
DR   EMBL; DQ115391; AAZ22473.1; -; Genomic_DNA.
DR   EMBL; Z72845; CAA97062.1; -; Genomic_DNA.
DR   PIR; S64354; S64354.
DR   RefSeq; NP_011574.1; -.
DR   DIP; DIP:2799N; -.
DR   IntAct; P53045; 111.
DR   PeptideAtlas; P53045; -.
DR   PRIDE; P53045; -.
DR   Ensembl; YGR060W; Saccharomyces cerevisiae.
DR   GeneID; 852951; -.
DR   GenomeReviews; Y13135_GR; YGR060W.
DR   KEGG; sce:YGR060W; -.
DR   NMPDR; fig|4932.3.peg.2690; -.
DR   CYGD; YGR060w; -.
DR   SGD; S000003292; ERG25.
DR   HOGENOM; P53045; -.
DR   OMA; P53045; EDTWHYW.
DR   BRENDA; 1.14.13.72; 250.
DR   NextBio; 972708; -.
DR   GermOnline; YGR060W; Saccharomyces cerevisiae.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR   GO; GO:0000254; F:C-4 methylsterol oxidase activity; IDA:SGD.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR006694; Fatty_acid_hydroxylase.
DR   Pfam; PF04116; FA_hydroxylase; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Endoplasmic reticulum; Iron; Isopeptide bond;
KW   Lipid synthesis; Membrane; NAD; Oxidoreductase; Steroid biosynthesis;
KW   Sterol biosynthesis; Transmembrane; Ubl conjugation.
FT   CHAIN         1    309       C-4 methylsterol oxidase.
FT                                /FTId=PRO_0000117039.
FT   TRANSMEM     56     76       Potential.
FT   MOTIF       160    164       Histidine box-1.
FT   MOTIF       173    177       Histidine box-2.
FT   MOTIF       257    263       Histidine box-3.
FT   CROSSLNK     96     96       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ubiquitin).
SQ   SEQUENCE   309 AA;  36479 MW;  E0422C416DD17794 CRC64;
     MSAVFNNATL SGLVQASTYS QTLQNVAHYQ PQLNFMEKYW AAWYSYMNND VLATGLMFFL
     LHEFMYFFRC LPWFIIDQIP YFRRWKLQPT KIPSAKEQLY CLKSVLLSHF LVEAIPIWTF
     HPMCEKLGIT VEVPFPSLKT MALEIGLFFV LEDTWHYWAH RLFHYGVFYK YIHKQHHRYA
     APFGLSAEYA HPAETLSLGF GTVGMPILYV MYTGKLHLFT LCVWITLRLF QAVDSHSGYD
     FPWSLNKIMP FWAGAEHHDL HHHYFIGNYA SSFRWWDYCL DTESGPEAKA SREERMKKRA
     ENNAQKKTN
//