Protein: 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 (P12684)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Function: HMG-CoA reductase; part of the first module of ergosterol biosynthesis pathway constitutes by the early steps of the pathway, conserved across all eukaryotes, and which results in the formation of mevalonate from acetyl-coenzyme A (acetyl-CoA). HMG1 and HMG2 catalyze the reduction of hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate that is the rate- limiting step within the first mosule. The first module starts with the action of the cytosolic acetyl-CoA acetyltransferase ERG10 that catalyzes the formation of acetoacetyl- CoA. The hydroxymethylglutaryl-CoA synthase ERG13 then condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA. The rate-limiting step of the early module is the reduction to mevalonate by the 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductases HMG1 and HMG2 which are derived from a single ancestral HMGR gene by gene duplication
Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Nucleus envelope
Sequence: MSLPLKTIVHLVKPFACTARFSARYPIHVIVVAVLLSAAAYLSVTQSYLNEWKLDSNQYSTYLSIKPDELFEKCTHYYRSPVSDTWKLLSSKEAADIYTPFHYYLSTISFQSKDNSTTLPSLDDVIYSVDHTRYLLSEEPKIPTELVSENGTKWRLRNNSNFILDLHNIYRNMVKQFSNKTSEFDQFDLFIILAAYLTLFYTLCCLFNDMRKIGSKFWLSFSALSNSACALYLSLYTTHSLLKKPASLLSLVIGLPFIVVIIGFKHKVRLAAFSLQKFHRISIDKKITVSNIIYEAMFQEGAYLIRDYLFYISSFIGCAIYARHLPGLVNFCILSTFMLVFDLLLSATFYSAILSMKLEINIIHRSTVIRQTLEEDGVVPTTADIIYKDETASEPHFLRSNVAIILGKASVIGLLLLINLYVFTDKLNATILNTVYFDSTIYSLPNFINYKDIGNLSNQVIISVLPKQYYTPLKKYHQIEDSVLLIIDSVSNAIRDQFISKLLFFAFAVSISINVYLLNAAKIHTGYMNFQPQSNKIDDLVVQQKSATIEFSETRSMPASSGLETPVTAKDIIISEEIQNNECVYALSSQDEPIRPLSNLVELMEKEQLKNMNNTEVSNLVVNGKLPLYSLEKKLEDTTRAVLVRRKALSTLAESPILVSEKLPFRNYDYDRVFGACCENVIGYMPIPVGVIGPLIIDGTSYHIPMATTEGCLVASAMRGCKAINAGGGATTVLTKDGMTRGPVVRFPTLIRSGACKIWLDSEEGQNSIKKAFNSTSRFARLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNYCTDKKPAAINWIEGRGKSVVAEATIPGDVVKSVLKSDVSALVELNISKNLVGSAMAGSVGGFNAHAANLVTALFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVGTIGGGTVLEPQGAMLDLLGVRGPHPTEPGANARQLARIIACAVLAGELSLCSALAAGHLVQSHMTHNRKTNKANELPQPSNKGPPCKTSALL
InterPro domains: - IPR023076: Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site (conserved_site) [797-1019]
- IPR025583: HMG-CoA reductase, N-terminal domain (domain) [10-159]
- IPR023282: Hydroxymethylglutaryl-CoA reductase, N-terminal (homologous_superfamily) [601-687]
- IPR009029: Hydroxymethylglutaryl-CoA reductase, class I/II, substrate-binding domain superfamily (homologous_superfamily) [598-1011]
- IPR009023: Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain superfamily (homologous_superfamily) [738-856]
- IPR023074: Hydroxymethylglutaryl-CoA reductase, class I/II, catalytic domain superfamily (homologous_superfamily) [688-1016]
- IPR000731: Sterol-sensing domain (domain) [188-356]
- IPR053958: HMGCR/SNAP/NPC1-like, sterol-sensing domain (domain) [213-361]
- IPR004554: Hydroxymethylglutaryl-CoA reductase, eukaryotic/archaeal type (family) [612-1021]
- IPR002202: Hydroxymethylglutaryl-CoA reductase, class I/II (family) [211-1024]
Interaction partners: - 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
- Hydroxymethylglutaryl-CoA synthase
- Mevalonate kinase
- ERAD-associated E3 ubiquitin-protein ligase HRD1
- Protein NSG1
- Squalene epoxidase ERG1
- Squalene synthase ERG9
- Isopentenyl-diphosphate delta-isomerase
- Farnesyl pyrophosphate synthase
- Cell division control protein 48
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0005515 (protein binding), GO:0016491 (oxidoreductase activity), GO:0016614 (oxidoreductase activity, acting on CH-OH group of donors), GO:0016616 (oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0044238 (primary metabolic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0019637 (organophosphate metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006066 (alcohol metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901135 (carbohydrate derivative metabolic process), GO:0035383 (thioester metabolic process), GO:0006793 (phosphorus metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006629 (lipid metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0055086 (nucleobase-containing small molecule metabolic process), GO:0044107 (cellular alcohol metabolic process), GO:0043603 (amide metabolic process), GO:0006790 (sulfur compound metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0006753 (nucleoside phosphate metabolic process), GO:0006720 (isoprenoid metabolic process), GO:0008202 (steroid metabolic process), GO:0006644 (phospholipid metabolic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0006796 (phosphate-containing compound metabolic process), GO:0072521 (purine-containing compound metabolic process), GO:0046165 (alcohol biosynthetic process), GO:0016128 (phytosteroid metabolic process), GO:0016125 (sterol metabolic process), GO:1902652 (secondary alcohol metabolic process), GO:0008204 (ergosterol metabolic process), GO:0006637 (acyl-CoA metabolic process), GO:0097384 (cellular lipid biosynthetic process), GO:0019693 (ribose phosphate metabolic process), GO:0090407 (organophosphate biosynthetic process), GO:0044108 (cellular alcohol biosynthetic process), GO:0008299 (isoprenoid biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0006696 (ergosterol biosynthetic process), GO:0009117 (nucleotide metabolic process), GO:0009240 (isopentenyl diphosphate biosynthetic process), GO:0006694 (steroid biosynthetic process), GO:0034032 (purine nucleoside bisphosphate metabolic process), GO:0016126 (sterol biosynthetic process), GO:0016129 (phytosteroid biosynthetic process), GO:0006084 (acetyl-CoA metabolic process), GO:1902653 (secondary alcohol biosynthetic process), GO:0033865 (nucleoside bisphosphate metabolic process), GO:0009259 (ribonucleotide metabolic process), GO:0008654 (phospholipid biosynthetic process), GO:0046490 (isopentenyl diphosphate metabolic process), GO:0006163 (purine nucleotide metabolic process), GO:0009150 (purine ribonucleotide metabolic process), GO:0033875 (ribonucleoside bisphosphate metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0034399 (nuclear periphery), GO:0031984 (organelle subcompartment), GO:0140535 (intracellular protein-containing complex), GO:0031975 (envelope), GO:1902494 (catalytic complex), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0000502 (proteasome complex), GO:1905368 (peptidase complex), GO:0043229 (intracellular organelle), GO:0098827 (endoplasmic reticulum subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0005635 (nuclear envelope), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005789 (endoplasmic reticulum membrane), GO:0070013 (intracellular organelle lumen), GO:1905369 (endopeptidase complex), GO:0005634 (nucleus), GO:0031981 (nuclear lumen)