HMDH_ASPTN
ID HMDH_ASPTN Reviewed; 1048 AA.
AC Q0C8L9;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000250|UniProtKB:Q4WHZ1};
DE Short=HMG-CoA reductase {ECO:0000250|UniProtKB:Q4WHZ1};
DE EC=1.1.1.34 {ECO:0000250|UniProtKB:Q4WHZ1};
GN ORFNames=ATEG_09965;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: HMG-CoA reductase; part of the first module of ergosterol
CC biosynthesis pathway that includes the early steps of the pathway,
CC conserved across all eukaryotes, and which results in the formation of
CC mevalonate from acetyl-coenzyme A (acetyl-CoA) (By similarity). In this
CC module, the cytosolic acetyl-CoA acetyltransferase catalyzes the
CC formation of acetoacetyl-CoA (By similarity). The
CC hydroxymethylglutaryl-CoA synthase then condenses acetyl-CoA with
CC acetoacetyl-CoA to form HMG-CoA (By similarity). The rate-limiting step
CC of the early module is the reduction to mevalonate by the 3-hydroxy-3-
CC methylglutaryl-coenzyme A (HMG-CoA) reductase (By similarity).
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10003};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; CH476609; EAU29414.1; -; Genomic_DNA.
DR RefSeq; XP_001209267.1; XM_001209267.1.
DR AlphaFoldDB; Q0C8L9; -.
DR SMR; Q0C8L9; -.
DR STRING; 341663.Q0C8L9; -.
DR PRIDE; Q0C8L9; -.
DR EnsemblFungi; EAU29414; EAU29414; ATEG_09965.
DR GeneID; 4319611; -.
DR VEuPathDB; FungiDB:ATEG_09965; -.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_0_0_1; -.
DR OMA; CVKLEIT; -.
DR OrthoDB; 907394at2759; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; -; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR025583; HMG-CoA_N_dom.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR023282; HMG_CoA_Rdtase_N.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF13323; HPIH; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS01192; HMG_COA_REDUCTASE_3; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
DR PROSITE; PS50156; SSD; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1048
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000283711"
FT TOPO_DOM 1..32
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 54..220
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 242..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..276
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..377
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..542
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 543..563
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 564..1048
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT DOMAIN 222..403
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT ACT_SITE 729
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 863
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 939
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1035
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 735..741
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 796..798
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 823..831
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 892..894
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1034..1035
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1039..1040
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 520
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1048 AA; 112181 MW; D7A3A8FF88A42B06 CRC64;
MDPVVKKPSP GGVQHRVTKG LRAIVGHACR HPIHTLLVTA LTAATTHLHV LEGTYQAAHR
GLAPWAKETP LNVQSFLCGS RTVTLGEASA WRWQIDDRPK VSEDGQSDFH WALVTLDLPG
ASVDASIPFL SNTLSEFLGA EQITPTPDSS PSPDHSALTF RVPYSQLDGF LQAVEIIPSE
KEDDSWRLRS PREEGSPTSL GHWVGSSWLS FLHRVKHAET VDLVIIGLSY LAMNMTVVSL
FRVMRQLGSR FWLATSVLLS GAFAFVLGLG ITTTCDVPVD MLLLFEGIPY LVLTVGFEKP
IQLTRAVLCV SEELRGGWQR PVPNGASSDD SRQSQLIPNI IQLAVDREGW YIVRSYLLEI
GALALGAVLR PNDSLGHFCF LAAWTLLIDA ILLFTFYATI LCVKLEITRI RSPGGLGQVN
AKHPSGIFGH KVKSTNITWW KLLTVGGFVL CHFLQLSPFF YRVMGEYMAN GTLPPTAVSP
FKEAANGLNE IYLTARVEGF ETRVTVLPPL QYALESAGFN ISATKRSTFD GVLDGLESPL
GRLCLMGALV VSLVLNNHLI HAARWHAWPQ ARESAVPDGS SLSVPCSATA PEVCTRPPEE
TEALLKSNQA ESLTDDELVE LCLRGKIAGY SLEKTLERIA AGSSCSVTRL DAFTRAVRIR
RAAVSKTPST QNLCSGLAES LLPYRDYNYE LVHGACCENV VGYLPLPLGV AGPMVIDGQA
LFIPMATTEG VLVASASRGC KAINAGGGAT TMLKGDGMTR GPCLRFPSAQ RAAEAQRWVE
SPLGHEVLAA AFNATSRFAR LQTLTVAQAG IYLYIRFRTT TGDAMGMNMI SKGVEKALEA
MAAEGGFPDM HTVTLSGNFC SDKKSAAINW IGGRGKSVIA EATIPAETVR QVLKTDVDAL
VELNTAKNLV GSAMAGSLGG FNAHASNLVQ AVFLATGQDP AQNVESSSCI TTMKNIDGNL
HIAVSMPSME VGTIGGGTIL EAQGAMLDLL GVRGAHATEP GANARRLARI VAAAVLAGEL
STCAALAAGH LVNAHMQHNR SAGATVKK
