HMDH_XENLA
ID HMDH_XENLA Reviewed; 883 AA.
AC P20715;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE EC=1.1.1.34 {ECO:0000250|UniProtKB:P04035};
GN Name=hmgcr;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=2307680; DOI=10.1016/s0021-9258(19)39608-5;
RA Chen H., Shapiro D.J.;
RT "Nucleotide sequence and estrogen induction of Xenopus laevis 3-hydroxy-3-
RT methylglutaryl-coenzyme A reductase.";
RL J. Biol. Chem. 265:4622-4629(1990).
CC -!- FUNCTION: Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA
CC (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of
CC cholesterol and other isoprenoids, thus plays a critical role in
CC cellular cholesterol homeostasis. {ECO:0000250|UniProtKB:P04035}.
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:0000250|UniProtKB:P04035};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15991;
CC Evidence={ECO:0000250|UniProtKB:P04035};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC -!- SUBUNIT: Homotetramer. Homodimer. {ECO:0000250|UniProtKB:P04035}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P00347}. Peroxisome membrane
CC {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P00347}.
CC -!- INDUCTION: By estrogen; in male liver. {ECO:0000269|PubMed:2307680}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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 EMBL; M29258; AAA49740.1; -; mRNA.
DR PIR; A35728; A35728.
DR RefSeq; NP_001081280.1; NM_001087811.1.
DR AlphaFoldDB; P20715; -.
DR SMR; P20715; -.
DR DNASU; 397750; -.
DR GeneID; 397750; -.
DR KEGG; xla:397750; -.
DR CTD; 397750; -.
DR Xenbase; XB-GENE-5840728; hmgcr.L.
DR OrthoDB; 907394at2759; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000186698; Chromosome 1L.
DR Bgee; 397750; Expressed in testis and 19 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
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:0005778; C:peroxisomal membrane; ISS:UniProtKB.
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; -; 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; 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 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; TIGR00920; 2A060605; 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 Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Peroxisome; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..883
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114426"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 10..39
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 40..56
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 57..78
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 79..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 90..114
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 115..123
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 124..149
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 150..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 160..187
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 188..191
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 192..220
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 221..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 250..276
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 277..316
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TRANSMEM 317..341
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT TOPO_DOM 342..883
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P00347"
FT REGION 373..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 554
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 686
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 762
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 861
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 883 AA; 96720 MW; 53D6D1D9294A9A1F CRC64;
MLSRLFRMHG QFVASHPWEV IVGTVTLTIC MMSMNMFTGN DKICGWNYAC PKFEEDVLSS
DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG
LNEALPFFLL LIDLSKASAL AKFALSSNSQ DEVRDNIARG MAILGPTFTL EALVECLVIG
VGTMSGVRQL EIMCCFGCMS VLANYFAFMT FFPACVSLVL ELSRESREGR PIWQLSQFAS
VLEEEEDNKP NPVTQRVKMI MSLGLVLVHA HSRWISEPSS QNSTSISDHE VTTMLDDMMP
KRVEPSMPLW QFYLSRMVTM DVEQIITLGL ALLLAVKYIF FEQTETESTF SMKNPIISPV
AVQKKQIESC CRREPEQEKT VHVSTTEEAS SKEETEAVIK PLPLETSPKA KFIVGDSSPL
ELSPEDKNTM FDLPEEPRPL DECVRILKNP DKGAQYLTDA EVISLVNAKH IPAYKLETMM
ESPREGVAIR RQMLSDKLPQ RSALQSLPYK NYNYSLVMGA CCENVIGYMP IPVGVAGPLL
LNNKEYQVPM ATTEGCLVAS TNRGCRAIML GGGAKSRVLA DGMTRGPVVR LPTACDAAEV
KAWLDSAEGF KVIKDAFDST SRFARLGRLQ NCVAGRNLYI RFQSKTGDAM GMNMISKVTE
QALARLQEEF PDLHVLAVSG NYCTDKKPAA INWIEGRGKS VVCEAIIPAK VVREVLKSST
EALVEVNINK NFIGSAMAGS IGGYNAHAAN IVTAIYIACG QDAAQNVGSS NCITIMEATG
PTYEDLYISC TMPSIEIGTV GGGTNLAPQQ ACLQMLGVQG ASTETPGKNA CQLAQIVCST
VMAGELSLMA ALAAGHLVKS HMVHNRSKIN LQDLPGTCTK KAA
