##gff-version 3 P04035 UniProtKB Chain 1 888 . . . ID=PRO_0000114419;Note=3-hydroxy-3-methylglutaryl-coenzyme A reductase P04035 UniProtKB Topological domain 1 9 . . . Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 10 39 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 40 56 . . . Note=Lumenal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 57 78 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 79 89 . . . Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 90 114 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 115 123 . . . Note=Lumenal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 124 149 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 150 159 . . . Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 160 187 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 188 191 . . . Note=Lumenal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 192 220 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 221 248 . . . Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 249 275 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 276 314 . . . Note=Lumenal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Transmembrane 315 339 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Topological domain 340 888 . . . Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P00347 P04035 UniProtKB Domain 61 218 . . . Note=SSD;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00199 P04035 UniProtKB Motif 75 78 . . . Note=INSIG-binding motif;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Active site 559 559 . . . Note=Charge relay system;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:10698924,ECO:0000303|PubMed:11349148;Dbxref=PMID:10698924,PMID:11349148 P04035 UniProtKB Active site 691 691 . . . Note=Charge relay system;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:10698924,ECO:0000303|PubMed:11349148;Dbxref=PMID:10698924,PMID:11349148 P04035 UniProtKB Active site 767 767 . . . Note=Charge relay system;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:10698924,ECO:0000303|PubMed:11349148;Dbxref=PMID:10698924,PMID:11349148 P04035 UniProtKB Active site 866 866 . . . Note=Proton donor;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU10003 P04035 UniProtKB Binding site 565 571 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Binding site 626 628 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Binding site 653 661 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Binding site 720 722 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Binding site 865 866 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Binding site 870 871 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:11349148,ECO:0007744|PDB:1DQA;Dbxref=PMID:11349148 P04035 UniProtKB Modified residue 504 504 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 P04035 UniProtKB Modified residue 872 872 . . . Note=Phosphoserine;Ontology_term=ECO:0000250,ECO:0007744;evidence=ECO:0000250|UniProtKB:P00347,ECO:0007744|PubMed:24275569;Dbxref=PMID:24275569 P04035 UniProtKB Glycosylation 281 281 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00498 P04035 UniProtKB Glycosylation 296 296 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00498 P04035 UniProtKB Cross-link 89 89 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Cross-link 248 248 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Alternative sequence 1 1 . . . ID=VSP_046492;Note=In isoform 3. M->MQWMSHTRERDAGSKDSVATM;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:14702039;Dbxref=PMID:14702039 P04035 UniProtKB Alternative sequence 522 574 . . . ID=VSP_002207;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:15489334;Dbxref=PMID:15489334 P04035 UniProtKB Natural variant 443 443 . . . ID=VAR_088585;Note=In LGMDR28%3B likely pathogenic%3B decreased hydroxymethylglutaryl-CoA reductase (NADPH) activity to 1%25 of wild-type activity%3B decreased thermal stability. R->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 443 443 . . . ID=VAR_088586;Note=In LGMDR28%3B likely pathogenic. R->W;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 467 467 . . . ID=VAR_088587;Note=In LGMDR28%3B uncertain significance. I->M;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 508 508 . . . ID=VAR_088588;Note=In LGMDR28%3B uncertain significance. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 515 515 . . . ID=VAR_088589;Note=In LGMDR28%3B uncertain significance. R->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 546 546 . . . ID=VAR_088590;Note=In LGMDR28%3B uncertain significance. L->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 623 623 . . . ID=VAR_088591;Note=In LGMDR28%3B likely pathogenic%3B decreased hydroxymethylglutaryl-CoA reductase (NADPH) activity to 50%25 of wild-type activity. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 638 638 . . . ID=VAR_011954;Note=I->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10391209;Dbxref=dbSNP:rs5908,PMID:10391209 P04035 UniProtKB Natural variant 792 792 . . . ID=VAR_088592;Note=In LGMDR28%3B likely pathogenic%3B decreased hydroxymethylglutaryl-CoA reductase (NADPH) activity to 25%25 of wild-type activity. Y->C;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:37167966;Dbxref=PMID:37167966 P04035 UniProtKB Natural variant 822 822 . . . ID=VAR_088593;Note=In LGMDR28%3B likely pathogenic%3B decreased hydroxymethylglutaryl-CoA reductase (NADPH) activity%3B reduced Vmax for hydroxymethylglutaryl-CoA reductase (NADPH) activity%3B has very low affinity for pravastatin. G->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:36745799;Dbxref=PMID:36745799 P04035 UniProtKB Mutagenesis 75 77 . . . Note=Reduced sterol-mediated release from the ER. Not deglycosylated in response to sterols. YIY->AIA;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Mutagenesis 89 89 . . . Note=Abolishes sterol-mediated ubiquitination and degradation%3B when associated with R-248. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Mutagenesis 248 248 . . . Note=Abolishes sterol-mediated ubiquitination and degradation%3B when associated with R-89. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19458199;Dbxref=PMID:19458199 P04035 UniProtKB Mutagenesis 807 807 . . . Note=Does not affect hydroxymethylglutaryl-CoA reductase activity. G->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21357570;Dbxref=PMID:21357570 P04035 UniProtKB Helix 445 453 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Turn 455 457 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 458 460 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 464 472 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 474 476 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CDA P04035 UniProtKB Helix 478 480 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 481 484 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 485 487 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 488 502 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 503 505 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 508 511 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 515 517 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1DQ9 P04035 UniProtKB Helix 519 521 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Turn 522 525 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 528 546 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 549 556 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 562 575 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 579 590 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 593 595 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 599 610 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 612 623 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 635 639 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 642 650 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 657 674 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 679 683 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 686 688 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1DQA P04035 UniProtKB Helix 695 700 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 703 712 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 714 719 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 721 723 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 725 736 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 738 742 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 746 752 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 753 763 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 768 770 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 771 774 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 777 785 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 790 800 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 804 806 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 807 810 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 812 820 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Beta strand 828 830 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 833 859 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2R4F P04035 UniProtKB Helix 862 869 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1DQA