CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002074
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 3-hydroxy-3-methylglutaryl-coenzyme A reductase 
Protein Synonyms/Alias
 HMG-CoA reductase 
Gene Name
 HMGCR 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
142SRASTLAKFALSSNSubiquitination[1, 2]
248VLEEEENKPNPVTQRubiquitination[1, 2]
288NSTADTSKVSLGLDEubiquitination[1, 2]
299GLDENVSKRIEPSVSubiquitination[1, 2]
362TSPVVTQKKVPDNCCubiquitination[1, 2]
363SPVVTQKKVPDNCCRubiquitination[1]
381MLVRNNQKCDSVEEEubiquitination[1]
396TGINRERKVEVIKPLubiquitination[1]
401ERKVEVIKPLVAETDubiquitination[1, 2]
460GNAEKGAKFLSDAEIubiquitination[1, 2]
474IIQLVNAKHIPAYKLubiquitination[1, 2]
480AKHIPAYKLETLMETubiquitination[1, 2]
502RRQLLSKKLSEPSSLubiquitination[1, 2]
553ACDSAEVKAWLETSEubiquitination[1]
566SEGFAVIKEAFDSTSubiquitination[1, 2]
580SRFARLQKLHTSIAGubiquitination[1, 2]
609MGMNMISKGTEKALSubiquitination[1, 2]
613MISKGTEKALSKLHEubiquitination[1]
617GTEKALSKLHEYFPEubiquitination[1]
639GNYCTDKKPAAINWIubiquitination[1]
651NWIEGRGKSVVCEAVubiquitination[1]
662CEAVIPAKVVREVLKubiquitination[1]
811LAAGHLVKSHMIHNRubiquitination[1]
820HMIHNRSKINLQDLQubiquitination[1]
832DLQGACTKKTA****ubiquitination[1]
833LQGACTKKTA*****ubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 61 218 SSD.
 REGION 340 449 Linker.
 REGION 450 888 Catalytic.
 MOTIF 75 78 INSIG-binding motif.
 ACT_SITE 559 559 Charge relay system.
 ACT_SITE 691 691 Charge relay system.
 ACT_SITE 767 767 Charge relay system.
 ACT_SITE 866 866 Proton donor.
 MOD_RES 872 872 Phosphoserine; by AMPK (By similarity).
 CARBOHYD 281 281 N-linked (GlcNAc...) (Potential).
 CARBOHYD 296 296 N-linked (GlcNAc...) (Potential).
 CARBOHYD 419 419 N-linked (GlcNAc...) (Potential).
 CARBOHYD 518 518 N-linked (GlcNAc...) (Potential).
 CARBOHYD 870 870 N-linked (GlcNAc...) (Potential).
 CROSSLNK 89 89 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 248 248 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 888 AA 
Protein Sequence
MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC PKFEEDVLSS 60
DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG 120
LNEALPFFLL LIDLSRASTL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG 180
VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR 240
VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTADTSKVS LGLDENVSKR 300
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL KNPITSPVVT 360
QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI KPLVAETDTP NRATFVVGNS 420
SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK 480
LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LLGGGASSRV LADGMTRGPV 540
VRLPRACDSA EVKAWLETSE GFAVIKEAFD STSRFARLQK LHTSIAGRNL YIRFQSRSGD 600
AMGMNMISKG TEKALSKLHE YFPEMQILAV SGNYCTDKKP AAINWIEGRG KSVVCEAVIP 660
AKVVREVLKT TTEAMIEVNI NKNLVGSAMA GSIGGYNAHA ANIVTAIYIA CGQDAAQNVG 720
SSNCITLMEA SGPTNEDLYI SCTMPSIEIG TVGGGTNLLP QQACLQMLGV QGACKDNPGE 780
NARQLARIVC GTVMAGELSL MAALAAGHLV KSHMIHNRSK INLQDLQGAC TKKTA 835 
Gene Ontology
 GO:0005789; C:endoplasmic reticulum membrane; TAS:UniProtKB.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
 GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:EC.
 GO:0042282; F:hydroxymethylglutaryl-CoA reductase activity; IDA:UniProtKB.
 GO:0070402; F:NADPH binding; IDA:UniProtKB.
 GO:0007568; P:aging; IEA:Compara.
 GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
 GO:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
 GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
 GO:0009790; P:embryo development; IEA:Compara.
 GO:0008299; P:isoprenoid biosynthetic process; IEA:Compara.
 GO:0045445; P:myoblast differentiation; IEA:Compara.
 GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Compara.
 GO:0043407; P:negative regulation of MAP kinase activity; IEA:Compara.
 GO:0010664; P:negative regulation of striated muscle cell apoptotic process; IEA:Compara.
 GO:0045908; P:negative regulation of vasodilation; IEA:Compara.
 GO:0061045; P:negative regulation of wound healing; IEA:Compara.
 GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Compara.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Compara.
 GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Compara.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0032874; P:positive regulation of stress-activated MAPK cascade; IEA:Compara.
 GO:0051262; P:protein tetramerization; IDA:UniProtKB.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0007584; P:response to nutrient; IEA:Compara.
 GO:0006743; P:ubiquinone metabolic process; IEA:Compara.
 GO:0008542; P:visual learning; IEA:Compara. 
Interpro
 IPR002202; HMG_CoA_Rdtase.
 IPR023074; HMG_CoA_Rdtase_cat.
 IPR023076; HMG_CoA_Rdtase_CS.
 IPR004554; HMG_CoA_Rdtase_eu_arc.
 IPR004816; HMG_CoA_Rdtase_metazoan.
 IPR023282; HMG_CoA_Rdtase_N.
 IPR009023; HMG_CoA_Rdtase_NAD(P)-bd.
 IPR009029; HMG_CoA_Rdtase_sub-bd.
 IPR000731; SSD. 
Pfam
 PF00368; HMG-CoA_red 
SMART
  
PROSITE
 PS00066; HMG_COA_REDUCTASE_1
 PS00318; HMG_COA_REDUCTASE_2
 PS01192; HMG_COA_REDUCTASE_3
 PS50065; HMG_COA_REDUCTASE_4
 PS50156; SSD 
PRINTS
 PR00071; HMGCOARDTASE.