LOCUS NP_000850 888 aa linear PRI 13-NOV-2008
DEFINITION 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1 [Homo
sapiens].
ACCESSION NP_000850
VERSION NP_000850.1 GI:4557643
DBSOURCE REFSEQ: accession NM_000859.2
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 888)
AUTHORS Burkhardt,R., Kenny,E.E., Lowe,J.K., Birkeland,A., Josowitz,R.,
Noel,M., Salit,J., Maller,J.B., Pe'er,I., Daly,M.J., Altshuler,D.,
Stoffel,M., Friedman,J.M. and Breslow,J.L.
TITLE Common SNPs in HMGCR in micronesians and whites associated with
LDL-cholesterol levels affect alternative splicing of exon13
JOURNAL Arterioscler. Thromb. Vasc. Biol. 28 (11), 2078-2084 (2008)
PUBMED 18802019
REMARK GeneRIF: Genome-wide association study of gene-disease association.
(HuGE Navigator)
REFERENCE 2 (residues 1 to 888)
AUTHORS Hosgood,H.D. III, Menashe,I., Shen,M., Yeager,M., Yuenger,J.,
Rajaraman,P., He,X., Chatterjee,N., Caporaso,N.E., Zhu,Y.,
Chanock,S.J., Zheng,T. and Lan,Q.
TITLE Pathway-based evaluation of 380 candidate genes and lung cancer
susceptibility suggests the importance of the cell cycle pathway
JOURNAL Carcinogenesis 29 (10), 1938-1943 (2008)
PUBMED 18676680
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
REFERENCE 3 (residues 1 to 888)
AUTHORS Donnelly,L.A., Doney,A.S., Dannfald,J., Whitley,A.L., Lang,C.C.,
Morris,A.D., Donnan,P.T. and Palmer,C.N.
TITLE A paucimorphic variant in the HMG-CoA reductase gene is associated
with lipid-lowering response to statin treatment in diabetes: a
GoDARTS study
JOURNAL Pharmacogenet. Genomics (2008) In press
PUBMED 18815589
REMARK GeneRIF: Observational study of gene-disease association,
gene-environment interaction, and pharmacogenomic / toxicogenomic.
(HuGE Navigator)
Publication Status: Available-Online prior to print
REFERENCE 4 (residues 1 to 888)
AUTHORS Knouff,C.W., Lim,N., Song,K., Yuan,X., Walker,M.C., Townsend,R.,
Waeber,G., Matthews,P.M., Vollenweider,P., Waterworth,D.M. and
Mooser,V.
TITLE Pharmacological effects of lipid-lowering drugs recapitulate with a
larger amplitude the phenotypic effects of common variants within
their target genes
JOURNAL Pharmacogenet. Genomics (2008) In press
PUBMED 18787507
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
Publication Status: Available-Online prior to print
REFERENCE 5 (residues 1 to 888)
AUTHORS Lu,Y., Dolle,M.E., Imholz,S., Slot,R.V., Verschuren,W.M.,
Wijmenga,C., Feskens,E.J. and Boer,J.M.
TITLE Multiple genetic variants along candidate pathways influence plasma
high-density lipoprotein cholesterol concentrations
JOURNAL J. Lipid Res. (2008) In press
PUBMED 18660489
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
Publication Status: Available-Online prior to print
REFERENCE 6 (residues 1 to 888)
AUTHORS Hodge,V.J., Gould,S.J., Subramani,S., Moser,H.W. and Krisans,S.K.
TITLE Normal cholesterol synthesis in human cells requires functional
peroxisomes
JOURNAL Biochem. Biophys. Res. Commun. 181 (2), 537-541 (1991)
PUBMED 1755834
REFERENCE 7 (residues 1 to 888)
AUTHORS Ramharack,R., Tam,S.P. and Deeley,R.G.
TITLE Characterization of three distinct size classes of human
3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA: expression of
the transcripts in hepatic and nonhepatic cells
JOURNAL DNA Cell Biol. 9 (9), 677-690 (1990)
PUBMED 1979742
REFERENCE 8 (residues 1 to 888)
AUTHORS Clarke,P.R. and Hardie,D.G.
TITLE Regulation of HMG-CoA reductase: identification of the site
phosphorylated by the AMP-activated protein kinase in vitro and in
intact rat liver
JOURNAL EMBO J. 9 (8), 2439-2446 (1990)
PUBMED 2369897
REFERENCE 9 (sites)
AUTHORS Clarke,P.R. and Hardie,D.G.
TITLE Regulation of HMG-CoA reductase: identification of the site
phosphorylated by the AMP-activated protein kinase in vitro and in
intact rat liver
JOURNAL EMBO J. 9 (8), 2439-2446 (1990)
PUBMED 2369897
REFERENCE 10 (residues 1 to 888)
AUTHORS Luskey,K.L. and Stevens,B.
TITLE Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved
domains responsible for catalytic activity and sterol-regulated
degradation
JOURNAL J. Biol. Chem. 260 (18), 10271-10277 (1985)
PUBMED 2991281
REFERENCE 11 (residues 1 to 888)
AUTHORS Humphries,S.E., Tata,F., Henry,I., Barichard,F., Holm,M., Junien,C.
and Williamson,R.
TITLE The isolation, characterisation, and chromosomal assignment of the
gene for human 3-hydroxy-3-methylglutaryl coenzyme A reductase,
(HMG-CoA reductase)
JOURNAL Hum. Genet. 71 (3), 254-258 (1985)
PUBMED 2998972
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from M62627.1, BC033692.1, M11058.1,
CN278665.1 and AA648735.1.
Summary: HMG-CoA reductase is the rate-limiting enzyme for
cholesterol synthesis and is regulated via a negative feedback
mechanism mediated by sterols and non-sterol metabolites derived
from mevalonate, the product of the reaction catalyzed by
reductase. Normally in mammalian cells this enzyme is suppressed by
cholesterol derived from the internalization and degradation of low
density lipoprotein (LDL) via the LDL receptor. Competitive
inhibitors of the reductase induce the expression of LDL receptors
in the liver, which in turn increases the catabolism of plasma LDL
and lowers the plasma concentration of cholesterol, an important
determinant of atherosclerosis. Alternatively spliced transcript
variants encoding different isoforms have been found for this gene.
[provided by RefSeq].
Transcript Variant: This variant (1) encodes the longer isoform
(1).
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the
Entrez Gene record to access additional publications.
FEATURES Location/Qualifiers
source 1..888
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="5"
/map="5q13.3-q14"
Protein 1..888
/product="3-hydroxy-3-methylglutaryl-Coenzyme A reductase
isoform 1"
/EC_number="1.1.1.34"
/note="hydroxymethylglutaryl-CoA reductase;
3-hydroxy-3-methylglutaryl CoA reductase (NADPH)"
/calculated_mol_wt=97345
Site 872
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[8]
/db_xref="HPRD:03382"
CDS 1..888
/gene="HMGCR"
/coded_by="NM_000859.2:157..2823"
/note="isoform 1 is encoded by transcript variant 1"
/db_xref="CCDS:CCDS4027.1"
/db_xref="GeneID:3156"
/db_xref="HGNC:5006"
/db_xref="HPRD:00836"
/db_xref="MIM:142910"
ORIGIN
1 mlsrlfrmhg lfvashpwev ivgtvtltic mmsmnmftgn nkicgwnyec pkfeedvlss
61 diiiltitrc iailyiyfqf qnlrqlgsky ilgiaglfti fssfvfstvv ihfldkeltg
121 lnealpffll lidlsrastl akfalssnsq devreniarg mailgptftl dalveclvig
181 vgtmsgvrql eimccfgcms vlanyfvfmt ffpacvslvl elsresregr piwqlshfar
241 vleeeenkpn pvtqrvkmim slglvlvhah srwiadpspq nstadtskvs lgldenvskr
301 iepsvslwqf ylskmismdi eqvitlslal llavkyiffe qtetestlsl knpitspvvt
361 qkkvpdnccr repmlvrnnq kcdsveeetg inrerkvevi kplvaetdtp nratfvvgns
421 slldtssvlv tqepeielpr eprpneeclq ilgnaekgak flsdaeiiql vnakhipayk
481 letlmether gvsirrqlls kklsepsslq ylpyrdynys lvmgaccenv igympipvgv
541 agplcldeke fqvpmatteg clvastnrgc raiglgggas srvladgmtr gpvvrlprac
601 dsaevkawle tsegfavike afdstsrfar lqklhtsiag rnlyirfqsr sgdamgmnmi
661 skgtekalsk lheyfpemqi lavsgnyctd kkpaainwie grgksvvcea vipakvvrev
721 lkttteamie vninknlvgs amagsiggyn ahaanivtai yiacgqdaaq nvgssncitl
781 measgptned lyisctmpsi eigtvgggtn llpqqaclqm lgvqgackdn pgenarqlar
841 ivcgtvmage lslmaalaag hlvkshmihn rskinlqdlq gactkkta
//