3-hydroxy-3-methylglutaryl-coenzyme A reductase
Details
- Name
- 3-hydroxy-3-methylglutaryl-coenzyme A reductase
- Synonyms
- 1.1.1.34
- HMG-CoA reductase
- Gene Name
- HMGCR
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0001146|3-hydroxy-3-methylglutaryl-coenzyme A reductase MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
- Number of residues
- 888
- Molecular Weight
- 97475.155
- Theoretical pI
- 6.72
- GO Classification
- Functionscoenzyme binding / hydroxymethylglutaryl-CoA reductase (NADPH) activity / hydroxymethylglutaryl-CoA reductase activity / NADPH bindingProcessesaging / cellular lipid metabolic process / cholesterol biosynthetic process / coenzyme A metabolic process / isoprenoid biosynthetic process / myoblast differentiation / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of MAP kinase activity / negative regulation of striated muscle cell apoptotic process / negative regulation of vasodilation / negative regulation of wound healing / positive regulation of cardiac muscle cell apoptotic process / positive regulation of ERK1 and ERK2 cascade / positive regulation of skeletal muscle tissue development / positive regulation of smooth muscle cell proliferation / positive regulation of stress-activated MAPK cascade / protein tetramerization / response to ethanol / response to nutrient / small molecule metabolic process / sterol biosynthetic process / ubiquinone metabolic process / visual learningComponentsendoplasmic reticulum / endoplasmic reticulum membrane / integral component of membrane / peroxisomal membrane
- General Function
- Nadph binding
- Specific Function
- Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
- Pfam Domain Function
- Transmembrane Regions
- 10-39 57-78 90-114 124-149 160-187 192-220 315-339
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0010398|3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA GGAGCTTGCACCAAGAAGACAGCCTGA
- Chromosome Location
- 5
- Locus
- 5q13.3-q14
- External Identifiers
Resource Link UniProtKB ID P04035 UniProtKB Entry Name HMDH_HUMAN GenBank Protein ID 306865 GenBank Gene ID M11058 GenAtlas ID HMGCR HGNC ID HGNC:5006 - General References
- Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Brown MS, Goldstein JL: Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res. 1980 Jul;21(5):505-17. [Article]
- Sever N, Yang T, Brown MS, Goldstein JL, DeBose-Boyd RA: Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mol Cell. 2003 Jan;11(1):25-33. [Article]
- Leichner GS, Avner R, Harats D, Roitelman J: Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation. Mol Biol Cell. 2009 Jul;20(14):3330-41. doi: 10.1091/mbc.E08-09-0953. Epub 2009 May 20. [Article]
- Leichner GS, Avner R, Harats D, Roitelman J: Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein. J Biol Chem. 2011 Sep 16;286(37):32150-61. doi: 10.1074/jbc.M111.278036. Epub 2011 Jul 21. [Article]
- Stormo C, Kringen MK, Grimholt RM, Berg JP, Piehler AP: A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus. BMC Mol Biol. 2012 Sep 18;13:29. doi: 10.1186/1471-2199-13-29. [Article]
- Nickerson ML, Bosley AD, Weiss JS, Kostiha BN, Hirota Y, Brandt W, Esposito D, Kinoshita S, Wessjohann L, Morham SG, Andresson T, Kruth HS, Okano T, Dean M: The UBIAD1 prenyltransferase links menaquinone-4 [corrected] synthesis to cholesterol metabolic enzymes. Hum Mutat. 2013 Feb;34(2):317-29. doi: 10.1002/humu.22230. Epub 2012 Nov 27. [Article]
- Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
- Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [Article]
- Istvan ES, Deisenhofer J: Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. [Article]
- Sarver RW, Bills E, Bolton G, Bratton LD, Caspers NL, Dunbar JB, Harris MS, Hutchings RH, Kennedy RM, Larsen SD, Pavlovsky A, Pfefferkorn JA, Bainbridge G: Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Med Chem. 2008 Jul 10;51(13):3804-13. doi: 10.1021/jm7015057. Epub 2008 Jun 10. [Article]
- Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00227 Lovastatin approved, investigational yes inhibitor Details DB00439 Cerivastatin approved, withdrawn yes inhibitor Details DB00641 Simvastatin approved yes inhibitor Details DB01076 Atorvastatin approved yes inhibitor Details DB01098 Rosuvastatin approved yes inhibitor Details DB00157 NADH approved, nutraceutical unknown Details DB01992 Coenzyme A investigational, nutraceutical unknown Details DB03169 (S)-Hmg-Coa experimental unknown Details DB03461 Nicotinamide adenine dinucleotide phosphate experimental unknown Details DB04377 Meglutol experimental unknown Details DB04447 1,4-Dithiothreitol experimental unknown Details DB01095 Fluvastatin approved yes inhibitor Details DB00175 Pravastatin approved yes inhibitor Details DB05317 TAK-475 investigational unknown Details DB06693 Mevastatin experimental yes inhibitor Details DB08860 Pitavastatin approved yes inhibitor Details DB09270 Ubidecarenone approved, investigational, nutraceutical no substrate Details DB09061 Cannabidiol approved, investigational unknown stimulator Details DB14011 Nabiximols investigational unknown stimulator Details DB14009 Medical Cannabis experimental, investigational unknown inducer Details