ID A0A3Q2E4K5_CYPVA Unreviewed; 827 AA.
AC A0A3Q2E4K5;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 1.
DT 27-MAR-2024, entry version 25.
DE RecName: Full=3-hydroxy-3-methylglutaryl coenzyme A reductase {ECO:0000256|RuleBase:RU361219};
DE Short=HMG-CoA reductase {ECO:0000256|RuleBase:RU361219};
DE EC=1.1.1.34 {ECO:0000256|RuleBase:RU361219};
OS Cyprinodon variegatus (Sheepshead minnow).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Ovalentaria; Atherinomorphae; Cyprinodontiformes; Cyprinodontidae;
OC Cyprinodon.
OX NCBI_TaxID=28743 {ECO:0000313|Ensembl:ENSCVAP00000027107.1, ECO:0000313|Proteomes:UP000265020};
RN [1] {ECO:0000313|Ensembl:ENSCVAP00000027107.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00023562};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15991;
CC Evidence={ECO:0000256|ARBA:ARBA00023562};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000256|ARBA:ARBA00005084, ECO:0000256|RuleBase:RU361219}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000256|ARBA:ARBA00004477, ECO:0000256|RuleBase:RU361219}; Multi-
CC pass membrane protein {ECO:0000256|ARBA:ARBA00004477,
CC ECO:0000256|RuleBase:RU361219}. Membrane
CC {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004141}. Peroxisome membrane
CC {ECO:0000256|ARBA:ARBA00004585}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004585}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family.
CC {ECO:0000256|ARBA:ARBA00007661, ECO:0000256|RuleBase:RU361219}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; A0A3Q2E4K5; -.
DR Ensembl; ENSCVAT00000029766.1; ENSCVAP00000027107.1; ENSCVAG00000013227.1.
DR GeneTree; ENSGT00940000155305; -.
DR OMA; YIYVQFK; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000265020; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; HMGR, N-terminal domain; 1.
DR Gene3D; 3.30.70.420; Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain; 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; IPR004816; HMG_CoA_Rdtase_metazoan.
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 NCBIfam; TIGR00920; 2A060605; 1.
DR NCBIfam; TIGR00533; HMG_CoA_R_NADP; 1.
DR PANTHER; PTHR10572; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE; 1.
DR PANTHER; PTHR10572:SF24; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF82866; Multidrug efflux transporter AcrB transmembrane domain; 1.
DR SUPFAM; SSF55035; NAD-binding domain of HMG-CoA reductase; 1.
DR SUPFAM; SSF56542; Substrate-binding domain of HMG-CoA reductase; 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 {ECO:0000256|ARBA:ARBA00022824,
KW ECO:0000256|RuleBase:RU361219};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00023011};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU361219};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|RuleBase:RU361219};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|RuleBase:RU361219}; Peroxisome {ECO:0000256|ARBA:ARBA00023140};
KW Reference proteome {ECO:0000313|Proteomes:UP000265020};
KW Steroid biosynthesis {ECO:0000256|ARBA:ARBA00023011};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Sterol biosynthesis {ECO:0000256|ARBA:ARBA00023011};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023011};
KW Transmembrane {ECO:0000256|RuleBase:RU361219};
KW Transmembrane helix {ECO:0000256|RuleBase:RU361219}.
FT TRANSMEM 20..38
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT TRANSMEM 89..114
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT DOMAIN 60..217
FT /note="SSD"
FT /evidence="ECO:0000259|PROSITE:PS50156"
FT REGION 352..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 827 AA; 89228 MW; 72748520203AAF90 CRC64;
MLARLFRLHG LLVASHPWEV IVGTLAVTIC LMNMNSFSTS SQMCSWDNCP KVKEEVPSSD
IISLTITRCM AIIYIYFQFK NLLQLGSKYI LGIAGLFTVF SSFVFSTVVI HFFGKELTGL
NEALPFFLLL IDLSKACTLA KFALSSNSQE EVRENISKGM AILGPTFTLD ALVECLVIGV
GTMSGVPQLE IMCCFGCMSV LANYFVFMTF FPACVSLVLE LSRESREGRP IWQMSHLAHV
LAEEEDNKPN PVTQRVKIIM SLGLALVHGL TRLTAEHAAH NRTVEGPMER LESAGTVWPQ
KVTSVELEHV ITLSLALLLA VKYVFFEQAD TESSLSLRSP INAASQIQKP RAAEDCCRRD
QSAPKPQRSS TDVLATSACS SGGCGPELRS VEECLAILSD PQRGPKMLTD AEVMNLVSLS
KIQNYKLEGV LETPERGVAI RREMLSSKLP VSSALAYLPY KDYDYSKVMG ACCENVIGYM
PVPVGVAGPL LLDKQQFHVP MATTEGCLVA STNRGCRAIW LSGGCNSRIL ADSMTRGPVV
RLPSACRAAE VKIWLETSDG FSMVKEAFDE TSRFARLEKL LVSVAGRNLY VRFQSQTGDA
MGMNMLSKGT EQALSRLKQH FPDIEVLSVS GNYCTDKKSA AINWILGRGK SAVCEATIPA
KVVKEVLKSS TAALVDLNIS KNLVGSAMAG SIGGFNAHAA NIVAAIYIAC GQDPAQTVGS
SSCITQMEAA GPSGEDLYIS CTMPSIELGT VGGGTILPPQ QACLQMLGVT SPKQPGENAC
QLARVVCATV LAGELSLMAA LAAGHLVKSH MTHNRSVYLL FGVCLKN
//
