ERG_META2
ID ERG_META2 Reviewed; 427 AA.
AC G4SW86;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Delta(14)-sterol reductase {ECO:0000303|PubMed:25307054, ECO:0000312|EMBL:CCE23001.1};
DE EC=1.3.1.70 {ECO:0000269|PubMed:25307054, ECO:0000312|EMBL:CCE23001.1};
DE AltName: Full=C-14 sterol reductase {ECO:0000305};
DE Short=C14SR {ECO:0000303|PubMed:25307054};
DE AltName: Full=MaSR1 {ECO:0000303|PubMed:25307054};
DE AltName: Full=Sterol C14-reductase {ECO:0000305};
GN Name=erg {ECO:0000312|EMBL:CCE23001.1};
GN OrderedLocusNames=MEALZ_1312 {ECO:0000312|EMBL:CCE23001.1};
OS Methylotuvimicrobium alcaliphilum (strain DSM 19304 / NCIMB 14124 / VKM
OS B-2133 / 20Z) (Methylomicrobium alcaliphilum).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Methylococcales;
OC Methylococcaceae; Methylotuvimicrobium.
OX NCBI_TaxID=1091494 {ECO:0000312|EMBL:CCE23001.1};
RN [1] {ECO:0000312|EMBL:CCE23001.1, ECO:0000312|Proteomes:UP000008315}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 19304 / NCIMB 14124 / VKM B-2133 / 20Z
RC {ECO:0000312|Proteomes:UP000008315};
RX PubMed=22207753; DOI=10.1128/jb.06392-11;
RA Vuilleumier S., Khmelenina V.N., Bringel F., Reshetnikov A.S., Lajus A.,
RA Mangenot S., Rouy Z., Op den Camp H.J., Jetten M.S., Dispirito A.A.,
RA Dunfield P., Klotz M.G., Semrau J.D., Stein L.Y., Barbe V., Medigue C.,
RA Trotsenko Y.A., Kalyuzhnaya M.G.;
RT "Genome sequence of the haloalkaliphilic methanotrophic bacterium
RT Methylomicrobium alcaliphilum 20Z.";
RL J. Bacteriol. 194:551-552(2012).
RN [2] {ECO:0007744|PDB:4QUV}
RP X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) IN COMPLEX WITH NADPH, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF
RP TYR-241; TRP-352; ASN-359; TYR-360; ASP-363; ARG-395; LYS-406; TYR-407 AND
RP TYR-414.
RC STRAIN=DSM 19304 / NCIMB 14124 / VKM B-2133 / 20Z
RC {ECO:0000303|PubMed:25307054};
RX PubMed=25307054; DOI=10.1038/nature13797;
RA Li X., Roberti R., Blobel G.;
RT "Structure of an integral membrane sterol reductase from Methylomicrobium
RT alcaliphilum.";
RL Nature 517:104-107(2015).
CC -!- FUNCTION: Reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-
CC 8,14,24-trienol to produce 4,4-dimethyl-cholesta-8,24-dienol.
CC Complements the deletion of the Delta(14)-sterol reductase gene ERG24
CC in yeast. {ECO:0000269|PubMed:25307054}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000269|PubMed:25307054};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:25307054}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:25307054}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; FO082060; CCE23001.1; -; Genomic_DNA.
DR RefSeq; WP_014147797.1; NC_016112.1.
DR PDB; 4QUV; X-ray; 2.74 A; A/B=1-427.
DR PDBsum; 4QUV; -.
DR AlphaFoldDB; G4SW86; -.
DR SMR; G4SW86; -.
DR STRING; 1091494.MEALZ_1312; -.
DR EnsemblBacteria; CCE23001; CCE23001; MEALZ_1312.
DR KEGG; mah:MEALZ_1312; -.
DR PATRIC; fig|271065.3.peg.1336; -.
DR HOGENOM; CLU_015631_0_3_6; -.
DR OMA; GWIILNC; -.
DR OrthoDB; 1171996at2; -.
DR BRENDA; 1.3.1.70; 8056.
DR Proteomes; UP000008315; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016126; P:sterol biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Lipid biosynthesis;
KW Lipid metabolism; Membrane; NADP; Nucleotide-binding; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..427
FT /note="Delta(14)-sterol reductase"
FT /id="PRO_0000436618"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 47..70
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 92..110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 132..141
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 163..197
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 219..226
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 248..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 284..291
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 313..356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 378
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25307054"
FT TOPO_DOM 400..427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:25307054"
FT BINDING 319
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 323
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 347
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 352
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 359..360
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 399
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 403..407
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT BINDING 414
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:25307054,
FT ECO:0007744|PDB:4QUV"
FT MUTAGEN 241
FT /note="Y->F: Loss of catalytic activity; when associated
FT with A-363."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 352
FT /note="W->A: Loss of catalytic activity; when associated
FT with A-414."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 359
FT /note="N->A: Loss of catalytic activity; when associated
FT with A-360."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 360
FT /note="Y->A: Loss of catalytic activity; when associated
FT with A-359."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 363
FT /note="D->A: Loss of catalytic activity; when associated
FT with F-241."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 395
FT /note="R->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 406
FT /note="K->A: Loss of catalytic activity; when associated
FT with A-407."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 407
FT /note="Y->A: Loss of catalytic activity; when associated
FT with A-406."
FT /evidence="ECO:0000269|PubMed:25307054"
FT MUTAGEN 414
FT /note="Y->A: Loss of catalytic activity; when associated
FT with A-352."
FT /evidence="ECO:0000269|PubMed:25307054"
FT HELIX 24..45
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 56..63
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 71..90
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:4QUV"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 113..129
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 142..163
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 196..224
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 229..247
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 250..254
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 265..272
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 281..287
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 295..323
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:4QUV"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 344..347
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 358..371
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:4QUV"
FT HELIX 383..417
FT /evidence="ECO:0007829|PDB:4QUV"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:4QUV"
SQ SEQUENCE 427 AA; 49418 MW; 5F0862CDBC6863F5 CRC64;
MSEQESRDNA AVDAVRQKYG FGFSWLVLMI ALPPLVYYLW ICVTYYQGEL VFTSDAAAWR
RFWSHVAPPT WHAAGLYAAW FLGQAALQVW APGPTVQGMK LPDGSRLDYR MNGIFSFLFT
LAVVFGLVTM GWLDATVLYD QLGPLLTVVN IFTFVFAGFL YFWGLNGKQW ERPTGRPFYD
YFMGTALNPR IGSLDLKLFC EARPGMIFWL LMNLSMAAKQ YELHGTVTVP MLLVVGFQSF
YLIDYFIHEE AVLTTWDIKH EKFGWMLCWG DLVWLPFTYT LQAQYLVHHT HDLPVWGIIA
IVALNLAGYA IFRGANIQKH HFRRDPNRIV WGKPAKYIKT KQGSLLLTSG WWGIARHMNY
FGDLMIALSW CLPAAFGSPI PYFHIVYFTI LLLHREKRDD AMCLAKYGED WLQYRKKVPW
RIVPKIY
