ID A0A2K5YAY7_MANLE Unreviewed; 835 AA.
AC A0A2K5YAY7;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 28.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000256|ARBA:ARBA00016920};
DE EC=1.1.1.34 {ECO:0000256|ARBA:ARBA00012999};
GN Name=HMGCR {ECO:0000313|Ensembl:ENSMLEP00000012718.1};
OS Mandrillus leucophaeus (Drill) (Papio leucophaeus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Mandrillus.
OX NCBI_TaxID=9568 {ECO:0000313|Ensembl:ENSMLEP00000012718.1, ECO:0000313|Proteomes:UP000233140};
RN [1] {ECO:0000313|Ensembl:ENSMLEP00000012718.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000256|ARBA:ARBA00004477}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004477}. 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}.
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 RefSeq; XP_011851918.1; XM_011996528.1.
DR AlphaFoldDB; A0A2K5YAY7; -.
DR Ensembl; ENSMLET00000036153.1; ENSMLEP00000012718.1; ENSMLEG00000030530.1.
DR GeneID; 105551327; -.
DR CTD; 3156; -.
DR GeneTree; ENSGT00940000155305; -.
DR OMA; GFAVMKE; -.
DR OrthoDB; 816560at2759; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000233140; 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 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; 2.
DR PROSITE; PS50156; SSD; 1.
PE 3: Inferred from homology;
KW Cholesterol biosynthesis {ECO:0000256|ARBA:ARBA00022778};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022778};
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022955};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00022955};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Peroxisome {ECO:0000256|ARBA:ARBA00023140};
KW Reference proteome {ECO:0000313|Proteomes:UP000233140};
KW Steroid biosynthesis {ECO:0000256|ARBA:ARBA00022955};
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|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT TRANSMEM 20..37
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 57..78
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 90..113
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 157..182
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 202..220
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 61..218
FT /note="SSD"
FT /evidence="ECO:0000259|PROSITE:PS50156"
SQ SEQUENCE 835 AA; 91815 MW; E1043722DDA4742C CRC64;
MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC PKFEEDVLSS
DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG
LNEALPFFLL LIDLSRASAL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG
VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR
VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTADTSKVS LGLDENVSKR
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QAETESTLSL KNPITSPVVT
QKKVPDNCCR REPVLVRNNQ KCDSIEEETG INRERKVEVI KPLVAETDTP NKATFVVGNS
SLLDTSSVLV TQEPEIELPG EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK
LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LLGGGASSRV LADGMTRGPV
VRLPRACDSA EVKAWLETSE GFAVIKEAFD STSRFARLQK LHTSIAGRNL YIRFQSRSGD
AMGMNMISKG TEKALSKLHE YFPEMQILAV SGNYCTDKKP AAINWIEGRG KSVVCEAVIP
AKVVREVLKT TTEAMIEVNI NKNLVGSAMA GSIGGYNAHA ANIVTAIYIA CGQDAAQNVG
SSNCITLMEA SGPTNEDLYI SCTMPSIEIG TVGGGTNLLP QQACLQMLGV QGACKDNPGE
NARQLARIVC GTVMAGELSL MAALAAGHLV KSHMIHNRSK INLQDLQGAC TKKTA
//
