P12684 · HMDH2_YEAST
- Protein3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
- GeneHMG2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1045 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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) (PubMed:3065625, PubMed:3526336).
HMG1 and HMG2 catalyze the reduction of hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate that is the rate-limiting step within the first mosule (PubMed:3526336).
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 (PubMed:32679672).
HMG1 and HMG2 catalyze the reduction of hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate that is the rate-limiting step within the first mosule (PubMed:3526336).
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 (PubMed:32679672).
Miscellaneous
Present with 149 molecules/cell in log phase SD medium.
Catalytic activity
- (R)-mevalonate + CoA + 2 NADP+ = (3S)-hydroxy-3-methylglutaryl-CoA + 2 H+ + 2 NADPHThis reaction proceeds in the backward direction.
Pathway
Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 710 | Charge relay system | ||||
Sequence: E | ||||||
Binding site | 716-722 | CoA (UniProtKB | ChEBI) | ||||
Sequence: SAMRGCK | ||||||
Binding site | 777-779 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SRF | ||||||
Binding site | 804-812 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: DAMGMNMIS | ||||||
Active site | 844 | Charge relay system | ||||
Sequence: K | ||||||
Binding site | 873-875 | CoA (UniProtKB | ChEBI) | ||||
Sequence: VLK | ||||||
Active site | 920 | Charge relay system | ||||
Sequence: D | ||||||
Binding site | 1015-1016 | CoA (UniProtKB | ChEBI) | ||||
Sequence: SH | ||||||
Active site | 1016 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 1020-1021 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: NR |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | nuclear envelope | |
Cellular Component | nuclear periphery | |
Cellular Component | peroxisomal membrane | |
Cellular Component | proteasome complex | |
Molecular Function | hydroxymethylglutaryl-CoA reductase (NADPH) activity | |
Biological Process | coenzyme A metabolic process | |
Biological Process | ergosterol biosynthetic process | |
Biological Process | isoprenoid biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
- EC number
- Short namesHMG-CoA reductase 2
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP12684
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-24 | Cytoplasmic | ||||
Sequence: MSLPLKTIVHLVKPFACTARFSAR | ||||||
Transmembrane | 25-45 | Helical | ||||
Sequence: YPIHVIVVAVLLSAAAYLSVT | ||||||
Topological domain | 46-186 | Lumenal | ||||
Sequence: QSYLNEWKLDSNQYSTYLSIKPDELFEKCTHYYRSPVSDTWKLLSSKEAADIYTPFHYYLSTISFQSKDNSTTLPSLDDVIYSVDHTRYLLSEEPKIPTELVSENGTKWRLRNNSNFILDLHNIYRNMVKQFSNKTSEFDQ | ||||||
Transmembrane | 187-207 | Helical | ||||
Sequence: FDLFIILAAYLTLFYTLCCLF | ||||||
Topological domain | 208-216 | Cytoplasmic | ||||
Sequence: NDMRKIGSK | ||||||
Transmembrane | 217-237 | Helical | ||||
Sequence: FWLSFSALSNSACALYLSLYT | ||||||
Topological domain | 238-243 | Lumenal | ||||
Sequence: THSLLK | ||||||
Transmembrane | 244-264 | Helical | ||||
Sequence: KPASLLSLVIGLPFIVVIIGF | ||||||
Topological domain | 265-301 | Cytoplasmic | ||||
Sequence: KHKVRLAAFSLQKFHRISIDKKITVSNIIYEAMFQEG | ||||||
Transmembrane | 302-322 | Helical | ||||
Sequence: AYLIRDYLFYISSFIGCAIYA | ||||||
Topological domain | 323-324 | Lumenal | ||||
Sequence: RH | ||||||
Transmembrane | 325-345 | Helical | ||||
Sequence: LPGLVNFCILSTFMLVFDLLL | ||||||
Topological domain | 346-402 | Cytoplasmic | ||||
Sequence: SATFYSAILSMKLEINIIHRSTVIRQTLEEDGVVPTTADIIYKDETASEPHFLRSNV | ||||||
Transmembrane | 403-423 | Helical | ||||
Sequence: AIILGKASVIGLLLLINLYVF | ||||||
Topological domain | 424-497 | Lumenal | ||||
Sequence: TDKLNATILNTVYFDSTIYSLPNFINYKDIGNLSNQVIISVLPKQYYTPLKKYHQIEDSVLLIIDSVSNAIRDQ | ||||||
Transmembrane | 498-518 | Helical | ||||
Sequence: FISKLLFFAFAVSISINVYLL | ||||||
Topological domain | 519-1045 | Cytoplasmic | ||||
Sequence: NAAKIHTGYMNFQPQSNKIDDLVVQQKSATIEFSETRSMPASSGLETPVTAKDIIISEEIQNNECVYALSSQDEPIRPLSNLVELMEKEQLKNMNNTEVSNLVVNGKLPLYSLEKKLEDTTRAVLVRRKALSTLAESPILVSEKLPFRNYDYDRVFGACCENVIGYMPIPVGVIGPLIIDGTSYHIPMATTEGCLVASAMRGCKAINAGGGATTVLTKDGMTRGPVVRFPTLIRSGACKIWLDSEEGQNSIKKAFNSTSRFARLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNYCTDKKPAAINWIEGRGKSVVAEATIPGDVVKSVLKSDVSALVELNISKNLVGSAMAGSVGGFNAHAANLVTALFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVGTIGGGTVLEPQGAMLDLLGVRGPHPTEPGANARQLARIIACAVLAGELSLCSALAAGHLVQSHMTHNRKTNKANELPQPSNKGPPCKTSALL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
When both HMG1 and HMG2 are deleted, cells are unable to undergo spore germination and vegetative growth.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 188 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: D → A | ||||||
Mutagenesis | 191 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: I → A | ||||||
Mutagenesis | 192 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: I → A | ||||||
Mutagenesis | 202-205 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: TLCC → AAAA | ||||||
Mutagenesis | 215 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: S → A or T | ||||||
Mutagenesis | 217 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: F → L | ||||||
Mutagenesis | 219 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: L → F | ||||||
Mutagenesis | 231 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: L → A | ||||||
Mutagenesis | 256 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: P → A | ||||||
Mutagenesis | 257 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: F → L | ||||||
Mutagenesis | 262 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: I → A | ||||||
Mutagenesis | 328 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: L → A | ||||||
Mutagenesis | 342 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: D → A | ||||||
Mutagenesis | 345 | Leads to normal response to the FPP-derived signal but no response to the oxysterol signal. | ||||
Sequence: L → A | ||||||
Mutagenesis | 350 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 354 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: L → A | ||||||
Mutagenesis | 359 | Leads to increased stability and reduced response to degradation signals. | ||||
Sequence: E → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 15 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000114457 | 1-1045 | 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 | |||
Sequence: MSLPLKTIVHLVKPFACTARFSARYPIHVIVVAVLLSAAAYLSVTQSYLNEWKLDSNQYSTYLSIKPDELFEKCTHYYRSPVSDTWKLLSSKEAADIYTPFHYYLSTISFQSKDNSTTLPSLDDVIYSVDHTRYLLSEEPKIPTELVSENGTKWRLRNNSNFILDLHNIYRNMVKQFSNKTSEFDQFDLFIILAAYLTLFYTLCCLFNDMRKIGSKFWLSFSALSNSACALYLSLYTTHSLLKKPASLLSLVIGLPFIVVIIGFKHKVRLAAFSLQKFHRISIDKKITVSNIIYEAMFQEGAYLIRDYLFYISSFIGCAIYARHLPGLVNFCILSTFMLVFDLLLSATFYSAILSMKLEINIIHRSTVIRQTLEEDGVVPTTADIIYKDETASEPHFLRSNVAIILGKASVIGLLLLINLYVFTDKLNATILNTVYFDSTIYSLPNFINYKDIGNLSNQVIISVLPKQYYTPLKKYHQIEDSVLLIIDSVSNAIRDQFISKLLFFAFAVSISINVYLLNAAKIHTGYMNFQPQSNKIDDLVVQQKSATIEFSETRSMPASSGLETPVTAKDIIISEEIQNNECVYALSSQDEPIRPLSNLVELMEKEQLKNMNNTEVSNLVVNGKLPLYSLEKKLEDTTRAVLVRRKALSTLAESPILVSEKLPFRNYDYDRVFGACCENVIGYMPIPVGVIGPLIIDGTSYHIPMATTEGCLVASAMRGCKAINAGGGATTVLTKDGMTRGPVVRFPTLIRSGACKIWLDSEEGQNSIKKAFNSTSRFARLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNYCTDKKPAAINWIEGRGKSVVAEATIPGDVVKSVLKSDVSALVELNISKNLVGSAMAGSVGGFNAHAANLVTALFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVGTIGGGTVLEPQGAMLDLLGVRGPHPTEPGANARQLARIIACAVLAGELSLCSALAAGHLVQSHMTHNRKTNKANELPQPSNKGPPCKTSALL | ||||||
Glycosylation | 115 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 150 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 158 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 179 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 428 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 455 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 565 | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P12684 | HMG1 P12683 | 6 | EBI-8384, EBI-8377 | |
BINARY | P12684 | NSG1 P38837 | 3 | EBI-8384, EBI-24733 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 188-356 | SSD | ||||
Sequence: DLFIILAAYLTLFYTLCCLFNDMRKIGSKFWLSFSALSNSACALYLSLYTTHSLLKKPASLLSLVIGLPFIVVIIGFKHKVRLAAFSLQKFHRISIDKKITVSNIIYEAMFQEGAYLIRDYLFYISSFIGCAIYARHLPGLVNFCILSTFMLVFDLLLSATFYSAILSM | ||||||
Compositional bias | 1018-1038 | Polar residues | ||||
Sequence: THNRKTNKANELPQPSNKGPP | ||||||
Region | 1018-1045 | Disordered | ||||
Sequence: THNRKTNKANELPQPSNKGPPCKTSALL |
Domain
The sterol-sensing domain (SSD) is required for sterol pathway signals to stimulate hmg2 ER-associated degradation and detects both geranylgeranyl pyrophosphate and a secondary oxysterol signal.
Sequence similarities
Belongs to the HMG-CoA reductase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,045
- Mass (Da)115,692
- Last updated1989-10-01 v1
- Checksum1FD9DCD3AC01B15E
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 29 | in Ref. 4; AAT92819 | ||||
Sequence: V → A | ||||||
Compositional bias | 1018-1038 | Polar residues | ||||
Sequence: THNRKTNKANELPQPSNKGPP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M22255 EMBL· GenBank· DDBJ | AAA34677.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U22382 EMBL· GenBank· DDBJ | AAB67527.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY692800 EMBL· GenBank· DDBJ | AAT92819.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006945 EMBL· GenBank· DDBJ | DAA09750.1 EMBL· GenBank· DDBJ | Genomic DNA |