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Database: UniProt
Entry: P04035
LinkDB: P04035
Original site: P04035 
ID   HMDH_HUMAN              Reviewed;         888 AA.
AC   P04035; B7Z3Y9; Q8N190;
DT   01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1986, sequence version 1.
DT   02-JUN-2021, entry version 234.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34 {ECO:0000269|PubMed:21357570, ECO:0000269|PubMed:2991281, ECO:0000269|PubMed:6995544};
GN   Name=HMGCR {ECO:0000312|HGNC:HGNC:5006};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=2991281;
RA   Luskey K.L., Stevens B.;
RT   "Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains
RT   responsible for catalytic activity and sterol-regulated degradation.";
RL   J. Biol. Chem. 260:10271-10277(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Nakajima T., Iwaki K., Hamakubo T., Kodama T., Emi M.;
RT   "Human HMG-CoA reductase gene.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D.,
RA   Toth E.J., Nickerson D.A.;
RL   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Blood;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=6995544;
RA   Brown M.S., Goldstein J.L.;
RT   "Multivalent feedback regulation of HMG CoA reductase, a control mechanism
RT   coordinating isoprenoid synthesis and cell growth.";
RL   J. Lipid Res. 21:505-517(1980).
RN   [8]
RP   INTERACTION WITH INSIG1, AND UBIQUITINATION.
RX   PubMed=12535518; DOI=10.1016/s1097-2765(02)00822-5;
RA   Sever N., Yang T., Brown M.S., Goldstein J.L., DeBose-Boyd R.A.;
RT   "Accelerated degradation of HMG CoA reductase mediated by binding of insig-
RT   1 to its sterol-sensing domain.";
RL   Mol. Cell 11:25-33(2003).
RN   [9]
RP   SUBCELLULAR LOCATION.
RX   PubMed=17180682; DOI=10.1007/s00418-006-0254-6;
RA   Kovacs W.J., Tape K.N., Shackelford J.E., Duan X., Kasumov T.,
RA   Kelleher J.K., Brunengraber H., Krisans S.K.;
RT   "Localization of the pre-squalene segment of the isoprenoid biosynthetic
RT   pathway in mammalian peroxisomes.";
RL   Histochem. Cell Biol. 127:273-290(2007).
RN   [10]
RP   INTERACTION WITH INSIG1, UBIQUITINATION AT LYS-89 AND LYS-248,
RP   GLYCOSYLATION, AND MUTAGENESIS OF 75-TYR--TYR-77; LYS-89 AND LYS-248.
RX   PubMed=19458199; DOI=10.1091/mbc.e08-09-0953;
RA   Leichner G.S., Avner R., Harats D., Roitelman J.;
RT   "Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic
RT   reticulum proteins, en route to proteasomal degradation.";
RL   Mol. Biol. Cell 20:3330-3341(2009).
RN   [11]
RP   UBIQUITINATION.
RX   PubMed=21778231; DOI=10.1074/jbc.m111.278036;
RA   Leichner G.S., Avner R., Harats D., Roitelman J.;
RT   "Metabolically regulated endoplasmic reticulum-associated degradation of 3-
RT   hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a
RT   geranylgeranylated protein.";
RL   J. Biol. Chem. 286:32150-32161(2011).
RN   [12]
RP   CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP   GLY-807.
RX   PubMed=21357570; DOI=10.1194/jlr.m011817;
RA   Cuccioloni M., Mozzicafreddo M., Spina M., Tran C.N., Falconi M.,
RA   Eleuteri A.M., Angeletti M.;
RT   "Epigallocatechin-3-gallate potently inhibits the in vitro activity of
RT   hydroxy-3-methyl-glutaryl-CoA reductase.";
RL   J. Lipid Res. 52:897-907(2011).
RN   [13]
RP   UBIQUITINATION.
RX   PubMed=22143767; DOI=10.1073/pnas.1112831108;
RA   Jo Y., Lee P.C., Sguigna P.V., DeBose-Boyd R.A.;
RT   "Sterol-induced degradation of HMG CoA reductase depends on interplay of
RT   two Insigs and two ubiquitin ligases, gp78 and Trc8.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:20503-20508(2011).
RN   [14]
RP   TISSUE SPECIFICITY (ISOFORMS 1; 2 AND 3), AND ALTERNATIVE SPLICING.
RX   PubMed=22989091; DOI=10.1186/1471-2199-13-29;
RA   Stormo C., Kringen M.K., Grimholt R.M., Berg J.P., Piehler A.P.;
RT   "A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice
RT   variant with an alternative exon 1 potentially encoding an extended N-
RT   terminus.";
RL   BMC Mol. Biol. 13:29-29(2012).
RN   [15]
RP   INTERACTION WITH UBIAD1.
RX   PubMed=23169578; DOI=10.1002/humu.22230;
RA   Nickerson M.L., Bosley A.D., Weiss J.S., Kostiha B.N., Hirota Y.,
RA   Brandt W., Esposito D., Kinoshita S., Wessjohann L., Morham S.G.,
RA   Andresson T., Kruth H.S., Okano T., Dean M.;
RT   "The UBIAD1 prenyltransferase links menaquione-4 synthesis to cholesterol
RT   metabolic enzymes.";
RL   Hum. Mutat. 34:317-329(2013).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-504, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888, AND SUBUNIT.
RX   PubMed=10698924; DOI=10.1093/emboj/19.5.819;
RA   Istvan E.S., Palnitkar M., Buchanan S.K., Deisenhofer J.;
RT   "Crystal structure of the catalytic portion of human HMG-CoA reductase:
RT   insights into regulation of activity and catalysis.";
RL   EMBO J. 19:819-830(2000).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888 IN COMPLEX WITH COENZYME A
RP   AND NADP.
RX   PubMed=11349148; DOI=10.1126/science.1059344;
RA   Istvan E.S., Deisenhofer J.;
RT   "Structural mechanism for statin inhibition of HMG-CoA reductase.";
RL   Science 292:1160-1164(2001).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 441-875 IN COMPLEX WITH
RP   STATIN-BASED INHIBITORS.
RX   PubMed=18540668; DOI=10.1021/jm7015057;
RA   Sarver R.W., Bills E., Bolton G., Bratton L.D., Caspers N.L., Dunbar J.B.,
RA   Harris M.S., Hutchings R.H., Kennedy R.M., Larsen S.D., Pavlovsky A.,
RA   Pfefferkorn J.A., Bainbridge G.;
RT   "Thermodynamic and structure guided design of statin based inhibitors of 3-
RT   hydroxy-3-methylglutaryl coenzyme A reductase.";
RL   J. Med. Chem. 51:3804-3813(2008).
RN   [21]
RP   VARIANT VAL-638.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [22]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
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 (PubMed:2991281, PubMed:21357570,
CC       PubMed:6995544). HMGCR is the main target of statins, a class of
CC       cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668).
CC       {ECO:0000269|PubMed:11349148, ECO:0000269|PubMed:18540668,
CC       ECO:0000269|PubMed:21357570, ECO:0000269|PubMed:2991281,
CC       ECO:0000269|PubMed:6995544}.
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:0000269|PubMed:21357570, ECO:0000269|PubMed:2991281,
CC         ECO:0000269|PubMed:6995544};
CC   -!- ACTIVITY REGULATION: Regulated by a negative feedback mechanism through
CC       sterols and non-sterol metabolites derived from mevalonate
CC       (PubMed:6995544). Phosphorylation at Ser-872 down-regulates the
CC       catalytic activity (By similarity). Inhibited by statins, a class of
CC       hypolipidemic agents used as pharmaceuticals to lower cholesterol
CC       levels in individuals at risk from cardiovascular disease due to
CC       hypercholesterolemia (PubMed:11349148, PubMed:18540668). Inhibition of
CC       HMGCR in the liver stimulates the LDL-receptors, which results in an
CC       increased clearance of LDL from the bloodstream and a decrease in blood
CC       cholesterol levels (PubMed:11349148, PubMed:18540668). The first
CC       results can be seen after one week of statin use and the effect is
CC       maximal after four to six weeks (PubMed:11349148, PubMed:18540668).
CC       {ECO:0000250|UniProtKB:P00347, ECO:0000269|PubMed:11349148,
CC       ECO:0000269|PubMed:18540668, ECO:0000303|PubMed:6995544}.
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SUBUNIT: Homotetramer (PubMed:10698924). Homodimer (PubMed:10698924).
CC       Interacts (via its SSD) with INSIG1; the interaction, accelerated by
CC       sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its
CC       ubiquitination by the sterol-mediated ERAD pathway (PubMed:12535518,
CC       PubMed:19458199). Interacts with UBIAD1 (PubMed:23169578).
CC       {ECO:0000269|PubMed:10698924, ECO:0000269|PubMed:11349148,
CC       ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:19458199,
CC       ECO:0000269|PubMed:23169578}.
CC   -!- INTERACTION:
CC       P04035; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-465513, EBI-2819725;
CC       P04035; Q9Y5Z9-1: UBIAD1; NbExp=5; IntAct=EBI-465513, EBI-6621921;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:17180682, ECO:0000305|PubMed:2991281}; Multi-pass
CC       membrane protein {ECO:0000250|UniProtKB:P00347}. Peroxisome membrane
CC       {ECO:0000269|PubMed:17180682}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P00347}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=HMGCR-1a {ECO:0000303|PubMed:22989091};
CC         IsoId=P04035-1; Sequence=Displayed;
CC       Name=2; Synonyms=HMGCR-1c {ECO:0000303|PubMed:22989091};
CC         IsoId=P04035-2; Sequence=VSP_002207;
CC       Name=3; Synonyms=HMGCR-1b {ECO:0000303|PubMed:22989091};
CC         IsoId=P04035-3; Sequence=VSP_046492;
CC   -!- TISSUE SPECIFICITY: [Isoform 1]: Ubiquitously expressed with the
CC       highest levels in the cerebellum, fetal brain, testis, skin and adrenal
CC       gland. {ECO:0000269|PubMed:22989091}.
CC   -!- TISSUE SPECIFICITY: [Isoform 2]: Detected in the cerebellum, fetal
CC       brain, testis and adrenal gland. {ECO:0000269|PubMed:22989091}.
CC   -!- TISSUE SPECIFICITY: [Isoform 3]: Low abundance except in skin,
CC       esophagus, and uterine cervix. {ECO:0000269|PubMed:22989091}.
CC   -!- PTM: N-glycosylated. Deglycosylated by NGLY1 on release from the
CC       endoplasmic reticulum (ER) in a sterol-mediated manner.
CC       {ECO:0000269|PubMed:19458199}.
CC   -!- PTM: Undergoes sterol-mediated ubiquitination and ER-associated
CC       degradation (ERAD) (PubMed:12535518, PubMed:19458199, PubMed:21778231).
CC       Accumulation of sterols in the endoplasmic reticulum (ER) membrane,
CC       triggers binding of the reductase to the ER membrane protein INSIG1 or
CC       INSIG2 (PubMed:12535518, PubMed:19458199, PubMed:21778231,
CC       PubMed:22143767). The INSIG1 binding leads to the recruitment of the
CC       ubiquitin ligase, AMFR/gp78, RNF139 or RNF145, initiating
CC       ubiquitination of the reductase (PubMed:12535518, PubMed:19458199,
CC       PubMed:21778231). The ubiquitinated reductase is then extracted from
CC       the ER membrane and delivered to cytosolic 26S proteosomes by a
CC       mechanism probably mediated by the ATPase Valosin-containing protein
CC       VCP/p97 (PubMed:12535518, PubMed:19458199, PubMed:21778231). The
CC       INSIG2-binding leads to the recruitment of the ubiquitin ligase RNF139,
CC       initiating ubiquitination of the reductase (PubMed:22143767). Lys-248
CC       is the main site of ubiquitination (PubMed:19458199). Ubiquitination is
CC       enhanced by the presence of a geranylgeranylated protein
CC       (PubMed:21778231). {ECO:0000269|PubMed:12535518,
CC       ECO:0000269|PubMed:19458199, ECO:0000269|PubMed:21778231,
CC       ECO:0000269|PubMed:22143767}.
CC   -!- PTM: Phosphorylated. Phosphorylation at Ser-872 reduces the catalytic
CC       activity. {ECO:0000250|UniProtKB:P00347}.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAH12375.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M11058; AAA52679.1; -; mRNA.
DR   EMBL; AF273765; AAG21343.1; -; Genomic_DNA.
DR   EMBL; AF273754; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273755; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273756; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273757; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273758; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273759; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273760; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273761; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273762; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273763; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AF273764; AAG21343.1; JOINED; Genomic_DNA.
DR   EMBL; AY321356; AAP72015.1; -; Genomic_DNA.
DR   EMBL; AK296499; BAH12375.1; ALT_FRAME; mRNA.
DR   EMBL; AC008897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC033692; AAH33692.1; -; mRNA.
DR   CCDS; CCDS4027.1; -. [P04035-1]
DR   CCDS; CCDS47234.1; -. [P04035-2]
DR   PIR; A00356; RDHUE.
DR   RefSeq; NP_000850.1; NM_000859.2. [P04035-1]
DR   RefSeq; NP_001124468.1; NM_001130996.1. [P04035-2]
DR   RefSeq; XP_011541659.1; XM_011543357.1. [P04035-3]
DR   RefSeq; XP_011541660.1; XM_011543358.1. [P04035-1]
DR   PDB; 1DQ8; X-ray; 2.10 A; A/B/C/D=426-888.
DR   PDB; 1DQ9; X-ray; 2.80 A; A/B/C/D=426-888.
DR   PDB; 1DQA; X-ray; 2.00 A; A/B/C/D=426-888.
DR   PDB; 1HW8; X-ray; 2.10 A; A/B/C/D=426-888.
DR   PDB; 1HW9; X-ray; 2.33 A; A/B/C/D=426-888.
DR   PDB; 1HWI; X-ray; 2.30 A; A/B/C/D=426-888.
DR   PDB; 1HWJ; X-ray; 2.26 A; A/B/C/D=426-888.
DR   PDB; 1HWK; X-ray; 2.22 A; A/B/C/D=426-888.
DR   PDB; 1HWL; X-ray; 2.10 A; A/B/C/D=426-888.
DR   PDB; 2Q1L; X-ray; 2.05 A; A/B/C/D=441-875.
DR   PDB; 2Q6B; X-ray; 2.00 A; A/B/C/D=441-875.
DR   PDB; 2Q6C; X-ray; 2.00 A; A/B/C/D=441-875.
DR   PDB; 2R4F; X-ray; 1.70 A; A/B/C/D=441-875.
DR   PDB; 3BGL; X-ray; 2.23 A; A/B/C/D=441-875.
DR   PDB; 3CCT; X-ray; 2.12 A; A/B/C/D=441-875.
DR   PDB; 3CCW; X-ray; 2.10 A; A/B/C/D=441-875.
DR   PDB; 3CCZ; X-ray; 1.70 A; A/B/C/D=441-875.
DR   PDB; 3CD0; X-ray; 2.40 A; A/B/C/D=441-875.
DR   PDB; 3CD5; X-ray; 2.39 A; A/B/C/D=441-875.
DR   PDB; 3CD7; X-ray; 2.05 A; A/B/C/D=441-875.
DR   PDB; 3CDA; X-ray; 2.07 A; A/B/C/D=441-875.
DR   PDB; 3CDB; X-ray; 2.30 A; A/B/C/D=441-875.
DR   PDBsum; 1DQ8; -.
DR   PDBsum; 1DQ9; -.
DR   PDBsum; 1DQA; -.
DR   PDBsum; 1HW8; -.
DR   PDBsum; 1HW9; -.
DR   PDBsum; 1HWI; -.
DR   PDBsum; 1HWJ; -.
DR   PDBsum; 1HWK; -.
DR   PDBsum; 1HWL; -.
DR   PDBsum; 2Q1L; -.
DR   PDBsum; 2Q6B; -.
DR   PDBsum; 2Q6C; -.
DR   PDBsum; 2R4F; -.
DR   PDBsum; 3BGL; -.
DR   PDBsum; 3CCT; -.
DR   PDBsum; 3CCW; -.
DR   PDBsum; 3CCZ; -.
DR   PDBsum; 3CD0; -.
DR   PDBsum; 3CD5; -.
DR   PDBsum; 3CD7; -.
DR   PDBsum; 3CDA; -.
DR   PDBsum; 3CDB; -.
DR   SMR; P04035; -.
DR   BioGRID; 109399; 88.
DR   ELM; P04035; -.
DR   IntAct; P04035; 18.
DR   STRING; 9606.ENSP00000287936; -.
DR   BindingDB; P04035; -.
DR   ChEMBL; CHEMBL402; -.
DR   DrugBank; DB03169; (S)-Hmg-Coa.
DR   DrugBank; DB04447; 1,4-Dithiothreitol.
DR   DrugBank; DB01076; Atorvastatin.
DR   DrugBank; DB09061; Cannabidiol.
DR   DrugBank; DB00439; Cerivastatin.
DR   DrugBank; DB01992; Coenzyme A.
DR   DrugBank; DB01095; Fluvastatin.
DR   DrugBank; DB00227; Lovastatin.
DR   DrugBank; DB14009; Medical Cannabis.
DR   DrugBank; DB04377; Meglutol.
DR   DrugBank; DB06693; Mevastatin.
DR   DrugBank; DB14011; Nabiximols.
DR   DrugBank; DB00157; NADH.
DR   DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR   DrugBank; DB08860; Pitavastatin.
DR   DrugBank; DB00175; Pravastatin.
DR   DrugBank; DB01098; Rosuvastatin.
DR   DrugBank; DB00641; Simvastatin.
DR   DrugBank; DB05317; TAK-475.
DR   DrugBank; DB09270; Ubidecarenone.
DR   DrugCentral; P04035; -.
DR   GuidetoPHARMACOLOGY; 639; -.
DR   SwissLipids; SLP:000001246; -.
DR   TCDB; 2.A.6.6.5; the resistance-nodulation-cell division (rnd) superfamily.
DR   GlyConnect; 983; 3 N-Linked glycans (1 site).
DR   GlyGen; P04035; 5 sites.
DR   iPTMnet; P04035; -.
DR   MetOSite; P04035; -.
DR   PhosphoSitePlus; P04035; -.
DR   SwissPalm; P04035; -.
DR   BioMuta; HMGCR; -.
DR   DMDM; 123343; -.
DR   EPD; P04035; -.
DR   jPOST; P04035; -.
DR   MassIVE; P04035; -.
DR   MaxQB; P04035; -.
DR   PaxDb; P04035; -.
DR   PeptideAtlas; P04035; -.
DR   PRIDE; P04035; -.
DR   ProteomicsDB; 51634; -. [P04035-1]
DR   ProteomicsDB; 51635; -. [P04035-2]
DR   Antibodypedia; 24380; 341 antibodies.
DR   DNASU; 3156; -.
DR   Ensembl; ENST00000287936; ENSP00000287936; ENSG00000113161. [P04035-1]
DR   Ensembl; ENST00000343975; ENSP00000340816; ENSG00000113161. [P04035-2]
DR   Ensembl; ENST00000511206; ENSP00000426745; ENSG00000113161. [P04035-1]
DR   Ensembl; ENST00000680940; ENSP00000505561; ENSG00000113161. [P04035-1]
DR   Ensembl; ENST00000681271; ENSP00000505805; ENSG00000113161. [P04035-1]
DR   Ensembl; ENST00000681410; ENSP00000506232; ENSG00000113161. [P04035-1]
DR   GeneID; 3156; -.
DR   KEGG; hsa:3156; -.
DR   UCSC; uc003kdp.4; human. [P04035-1]
DR   CTD; 3156; -.
DR   DisGeNET; 3156; -.
DR   GeneCards; HMGCR; -.
DR   HGNC; HGNC:5006; HMGCR.
DR   HPA; ENSG00000113161; Low tissue specificity.
DR   MIM; 142910; gene+phenotype.
DR   neXtProt; NX_P04035; -.
DR   OpenTargets; ENSG00000113161; -.
DR   PharmGKB; PA189; -.
DR   VEuPathDB; HostDB:ENSG00000113161.15; -.
DR   eggNOG; KOG2480; Eukaryota.
DR   GeneTree; ENSGT00940000155305; -.
DR   HOGENOM; CLU_001734_0_1_1; -.
DR   InParanoid; P04035; -.
DR   OMA; CENVLGY; -.
DR   OrthoDB; 907394at2759; -.
DR   PhylomeDB; P04035; -.
DR   TreeFam; TF105362; -.
DR   BioCyc; MetaCyc:HS03652-MONOMER; -.
DR   BRENDA; 1.1.1.34; 2681.
DR   PathwayCommons; P04035; -.
DR   Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR   Reactome; R-HSA-1989781; PPARA activates gene expression. [P04035-1]
DR   Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). [P04035-1]
DR   Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR   SABIO-RK; P04035; -.
DR   SIGNOR; P04035; -.
DR   UniPathway; UPA00058; UER00103.
DR   BioGRID-ORCS; 3156; 623 hits in 996 CRISPR screens.
DR   ChiTaRS; HMGCR; human.
DR   EvolutionaryTrace; P04035; -.
DR   GeneWiki; HMG-CoA_reductase; -.
DR   GenomeRNAi; 3156; -.
DR   Pharos; P04035; Tclin.
DR   PRO; PR:P04035; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P04035; protein.
DR   Bgee; ENSG00000113161; Expressed in adrenal tissue and 238 other tissues.
DR   ExpressionAtlas; P04035; baseline and differential.
DR   Genevisible; P04035; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR   GO; GO:0120225; F:coenzyme A binding; IDA:UniProtKB.
DR   GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IDA:UniProtKB.
DR   GO; GO:0042282; F:hydroxymethylglutaryl-CoA reductase activity; IDA:UniProtKB.
DR   GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IDA:CACAO.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR   GO; GO:1900222; P:negative regulation of amyloid-beta clearance; ISS:ARUK-UCL.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:ARUK-UCL.
DR   GO; GO:0050709; P:negative regulation of protein secretion; ISS:ARUK-UCL.
DR   GO; GO:0007399; P:nervous system development; TAS:Reactome.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; TAS:Reactome.
DR   GO; GO:0019222; P:regulation of metabolic process; TAS:Reactome.
DR   GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
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   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cholesterol biosynthesis;
KW   Cholesterol metabolism; Endoplasmic reticulum; Glycoprotein;
KW   Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW   Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   CHAIN           1..888
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114419"
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..248
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P00347"
FT   TRANSMEM        249..275
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P00347"
FT   TOPO_DOM        276..314
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:P00347"
FT   TRANSMEM        315..339
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P00347"
FT   TOPO_DOM        340..888
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P00347"
FT   DOMAIN          61..218
FT                   /note="SSD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT   NP_BIND         626..628
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   NP_BIND         653..661
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   NP_BIND         870..871
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   REGION          565..571
FT                   /note="Coenzyme A binding"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   REGION          720..722
FT                   /note="Coenzyme A binding"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   REGION          865..866
FT                   /note="Coenzyme A binding"
FT                   /evidence="ECO:0000269|PubMed:11349148,
FT                   ECO:0007744|PDB:1DQA"
FT   MOTIF           75..78
FT                   /note="INSIG-binding motif"
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   ACT_SITE        559
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000303|PubMed:10698924,
FT                   ECO:0000303|PubMed:11349148"
FT   ACT_SITE        691
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000303|PubMed:10698924,
FT                   ECO:0000303|PubMed:11349148"
FT   ACT_SITE        767
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000303|PubMed:10698924,
FT                   ECO:0000303|PubMed:11349148"
FT   ACT_SITE        866
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT   MOD_RES         504
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         872
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00347,
FT                   ECO:0007744|PubMed:24275569"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CROSSLNK        89
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   CROSSLNK        248
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   VAR_SEQ         1
FT                   /note="M -> MQWMSHTRERDAGSKDSVATM (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046492"
FT   VAR_SEQ         522..574
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_002207"
FT   VARIANT         638
FT                   /note="I -> V (in dbSNP:rs5908)"
FT                   /evidence="ECO:0000269|PubMed:10391209"
FT                   /id="VAR_011954"
FT   MUTAGEN         75..77
FT                   /note="YIY->AIA: Reduced sterol-mediated release from the
FT                   ER. Not deglycosylated in response to sterols."
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   MUTAGEN         89
FT                   /note="K->R: Abolishes sterol-mediated ubiquitination and
FT                   degradation; when associated with R-248."
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   MUTAGEN         248
FT                   /note="K->R: Abolishes sterol-mediated ubiquitination and
FT                   degradation; when associated with R-89."
FT                   /evidence="ECO:0000269|PubMed:19458199"
FT   MUTAGEN         807
FT                   /note="G->D: Does not affect hydroxymethylglutaryl-CoA
FT                   reductase activity."
FT                   /evidence="ECO:0000269|PubMed:21357570"
FT   HELIX           445..453
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   TURN            455..457
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           458..460
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           464..472
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          474..476
FT                   /evidence="ECO:0007829|PDB:3CDA"
FT   HELIX           478..480
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           481..484
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          485..487
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           488..502
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          503..505
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           508..511
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          515..517
FT                   /evidence="ECO:0007829|PDB:1DQ9"
FT   HELIX           519..521
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   TURN            522..525
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          528..546
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          549..556
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           562..575
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          579..590
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          593..595
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           599..610
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           612..623
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          635..639
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          642..650
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           657..674
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          679..683
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          686..688
FT                   /evidence="ECO:0007829|PDB:1DQA"
FT   HELIX           695..700
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          703..712
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           714..719
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          721..723
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           725..736
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           738..742
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          746..752
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           753..763
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           768..770
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           771..774
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          777..785
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          790..800
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          804..806
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           807..810
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           812..820
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   STRAND          828..830
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           833..859
FT                   /evidence="ECO:0007829|PDB:2R4F"
FT   HELIX           862..869
FT                   /evidence="ECO:0007829|PDB:1DQA"
SQ   SEQUENCE   888 AA;  97476 MW;  49B610DCCCFA26B6 CRC64;
     MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC PKFEEDVLSS
     DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG
     LNEALPFFLL LIDLSRASTL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG
     VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR
     VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTADTSKVS LGLDENVSKR
     IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL KNPITSPVVT
     QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI KPLVAETDTP NRATFVVGNS
     SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK
     LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LVMGACCENV IGYMPIPVGV
     AGPLCLDEKE FQVPMATTEG CLVASTNRGC RAIGLGGGAS SRVLADGMTR GPVVRLPRAC
     DSAEVKAWLE TSEGFAVIKE AFDSTSRFAR LQKLHTSIAG RNLYIRFQSR SGDAMGMNMI
     SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE GRGKSVVCEA VIPAKVVREV
     LKTTTEAMIE VNINKNLVGS AMAGSIGGYN AHAANIVTAI YIACGQDAAQ NVGSSNCITL
     MEASGPTNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM LGVQGACKDN PGENARQLAR
     IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GACTKKTA
//
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