ID D2H687_AILME Unreviewed; 888 AA.
AC D2H687;
DT 09-FEB-2010, integrated into UniProtKB/TrEMBL.
DT 09-FEB-2010, sequence version 1.
DT 27-MAR-2024, entry version 81.
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};
DE Flags: Fragment;
GN ORFNames=PANDA_005466 {ECO:0000313|EMBL:EFB14988.1};
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646 {ECO:0000313|EMBL:EFB14988.1};
RN [1] {ECO:0000313|EMBL:EFB14988.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
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}.
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DR EMBL; GL192524; EFB14988.1; -; Genomic_DNA.
DR RefSeq; XP_002917256.1; XM_002917210.3.
DR AlphaFoldDB; D2H687; -.
DR STRING; 9646.ENSAMEP00000000725; -.
DR GeneID; 100464316; -.
DR KEGG; aml:100464316; -.
DR CTD; 3156; -.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_0_1_1; -.
DR InParanoid; D2H687; -.
DR OMA; DCHIAMD; -.
DR OrthoDB; 816560at2759; -.
DR TreeFam; TF105362; -.
DR UniPathway; UPA00058; UER00103.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0120225; F:coenzyme A binding; IEA:Ensembl.
DR GO; GO:0030695; F:GTPase regulator activity; IEA:Ensembl.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0070402; F:NADPH binding; IEA:Ensembl.
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 GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IEA:Ensembl.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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 Cholesterol biosynthesis {ECO:0000256|ARBA:ARBA00022778};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022778};
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824,
KW ECO:0000256|RuleBase:RU361219};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022955};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00022955};
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 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|RuleBase:RU361219};
KW Transmembrane helix {ECO:0000256|RuleBase:RU361219}.
FT TRANSMEM 20..37
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT TRANSMEM 57..78
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT TRANSMEM 90..113
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT TRANSMEM 157..182
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT TRANSMEM 202..220
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361219"
FT DOMAIN 61..218
FT /note="SSD"
FT /evidence="ECO:0000259|PROSITE:PS50156"
FT NON_TER 888
FT /evidence="ECO:0000313|EMBL:EFB14988.1"
SQ SEQUENCE 888 AA; 97573 MW; 30A3C0F607F7D4E1 CRC64;
MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN DKICGWNYEC PKFEEDVLSS
DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG
LNEALPFFLL LIDLSRASAL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG
VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR
VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTAENSKVS LGLDENVSKR
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QAETESTLSL KNPITAPVAT
PKKVPDDCCR REPILVRNSQ QVHAAEEETR IKRERKVEVI KPVVAETDTP NRATFVVGDS
SSLDTSLELE TQEPEIELPM EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK
LETLMETHER GVSIRRQLLS RKLPEPSSLQ YLPYRDYNYS LVMGACCENV IGYMPIPVGV
AGPLRLDGKE FQVPMATTEG CLVASTNRGC RAIGLGGGAS SRILADGMTR GPVVRLPRAC
DSAEVKAWLE TPEGFTVMKE AFDSTSRFAR LQKLHMSMAG RNLYIRFQSR SGDAMGMNMI
SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE GRGKSVVCEA VIPAKVVREV
LKTTTEAMIE VNINKNLVGS AMAGSIGGYN AHAANIVTAI YIACGQDAAQ NVGSSNCITL
MEASGPTNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM LGVQGACKDN PGENARQLAR
IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GTCTKKAA
//
