HMDH_ASPTE
ID HMDH_ASPTE Reviewed; 1048 AA.
AC Q9Y7D2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 125.
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};
OS Aspergillus terreus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=33178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 20542 / MF4845;
RX PubMed=10334994; DOI=10.1126/science.284.5418.1368;
RA Kennedy J., Auclair K., Kendrew S.G., Park C., Vederas J.C.,
RA Hutchinson C.R.;
RT "Modulation of polyketide synthase activity by accessory proteins during
RT lovastatin biosynthesis.";
RL Science 284:1368-1372(1999).
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34556.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF141925; AAD34556.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; Q9Y7D2; -.
DR SMR; Q9Y7D2; -.
DR VEuPathDB; FungiDB:ATEG_09965; -.
DR UniPathway; UPA00058; UER00103.
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; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..1048
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114451"
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 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; 112451 MW; 8B7B3098ADA24BDE CRC64;
MDPVVRKPDP GGVQHRVTKA LRAIVGHACR HPIHTLLVTA LTAATTHLHV LEGTYQATHR
GLAPWAKETP LNVQSFLWGS RTVSLGEASA WKWQIDDRPK VPEDGQSDFH WALVTLDLPG
ASVDASIPFL SNTLSGFLGA EQTTPTPDSS PSPDHSALTF RVPYSQLDGF LQAVEIIPSE
KEDDSWRLRS PREEGSPRSL GHWLGSSWLS FLHRVHHAET VDLVIIGLSY LAMNMTVVSL
FRVMRHLGSR FWLAASVLLS GAFAFVLGLG ITTTCDVPVD MLLLFEGIPY LVLTVGFEKP
IQLTRAVLCV SEELWGGGQR QVPNGASSDD SRQNQLIPNI IQLAVDREGW YIVRSYLLEI
GALALGAVLR PKDSLGHFCF LAAWTLLIDA VLLFTFYATI LCVKLEITRI RSPGGLGQVN
AKHPSGIFGH KVKSTNITWW KLLTVGGFVL CHFLQLSPFF YRVMGEYMAN GTLPPTAVSP
FKEAANGLNE IYLTARVEGF ETRVTVLPPL QYVLESAGFN ISATKRSTFD GVLDGLESPL
GRLCLMGALV VSLVLNNHLI HAARWHAWPQ ARESAVPDGS YLSVPCSATA PEVCTRPPEE
TEALLKSNQA ESLTDDELVE LCLRGKIAGY SLEKTLERIA AGSSRSVTRL EAFTRAVRIR
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 GVRGAHSTEP GANARRLARI VAAAVLAGEL
STCAALAAGH LVNAHMQHNR SAGATVKK
