HMDH_AGRIP
ID HMDH_AGRIP Reviewed; 833 AA.
AC O76819;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE EC=1.1.1.34;
GN Name=HMGR;
OS Agrotis ipsilon (Black cutworm moth).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Noctuoidea;
OC Noctuidae; Noctuinae; Noctuini; Agrotis.
OX NCBI_TaxID=56364;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10971716; DOI=10.1046/j.1365-2583.2000.00200.x;
RA Duportets L., Belles X., Rossignol F., Couillaud F.;
RT "Molecular cloning and structural analysis of 3-hydroxy-3-methylglutaryl
RT coenzyme A reductase of the moth Agrotis ipsilon.";
RL Insect Mol. Biol. 9:385-392(2000).
CC -!- FUNCTION: Synthesis of mevalonate for the production of non-sterol
CC isoprenoids, which are essential for growth differentiation.
CC {ECO:0000250}.
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 -!- ACTIVITY REGULATION: The activity of HMG-CoA-reductase is suppressed by
CC exogenous mevalonate.
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; AJ009675; CAA08775.1; -; mRNA.
DR AlphaFoldDB; O76819; -.
DR SMR; O76819; -.
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: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; 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; 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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Glycoprotein; Isoprene biosynthesis; Membrane; NADP;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..833
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114429"
FT TRANSMEM 10..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 322..419
FT /note="Linker"
FT REGION 347..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 420..833
FT /note="Catalytic"
FT COMPBIAS 350..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 504
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 635
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 711
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 809
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 680
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 715
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 720
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 813
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 825
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 833 AA; 89790 MW; 7E9ADD4B4439A035 CRC64;
MKVWGAHGEF CARHQWEVIV ATLALLACAA SVERNGPGNR SEHCAGWARA CPGLEAEYQA
ADAVIMTFVR CAALLYAYYQ ISNLHKIASK YLLIIAGVFS TFASFIFTSA VASLFWSELA
SIKDAPFLFL LVADVARGAR MAKAGWSAGE DQGKRVGRAL ALLGPTATLD TLLAVLLVGV
GALSGVPRLE HMCTFACLAL LVDYLVFVTF YPACLSLVAD FASGRKEMSP DSPFSEADLK
PNPVVQRVKM IMAAGLLCVH LTSRWPWSSD NGIIEGPTDT LTPTSNDNIL LHSYVKWFSV
SADYIVIATL LCALIIKFVF FEEQRNWVID MNDMTVKEVV QEQARSKPKF SVGDDSNSEV
STQTEGVLED EWPTLSPSSS AAKLNSKKRP MAECLEIYRS EGACVSLSDE EVVMLVEQSH
IPLHRLEAVL GDPLRGVRLR RKVVGARFQT ELAIKQLPYL NYDYSKVLNA CCENVIGYVG
VPVGYAGPLV VDGKPYMIPM ATTEGALVAS TNRGAKAIGI RGVTSVVEDV GMTRAPAIKL
PNVVRAHECR QWIDNKDNYA VIKEAFDSTS RFARLQEIHI GVDGATLYLR FRATTGDAMG
MNMVSKGAEN ALKLLKNYFP DMEVISLSGN YCSDKKAAAI NWVKGRGKRV VCETTITSDS
LRTIFKTDAK TLARCNKIKN LSGSALAGSI GGNNAHAANM VTAIYIATGQ DPAQNVTSSN
CSTNMEVCGE NGEDLYVTCT MPSLEVGTVG GGTILTGQGA CLDILGVKGA GARPAENSAR
LASLICATVL AGELSLMAAL VNSDLVKSHM RHNRSTVNVQ VQAENITLKV PTL
