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Protein

3-hydroxy-3-methylglutaryl-coenzyme A reductase 1

Gene

HMG1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

One of 2 isozymes that catalyze the conversion of HMG-CoA to mevalonate. It is the rate-limiting enzyme of the sterol biosynthesis pathway. Involved in ergosterol biosynthesis.2 Publications

Catalytic activityi

(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.PROSITE-ProRule annotation

Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 3 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Acetyl-CoA acetyltransferase (ERG10)
  2. Hydroxymethylglutaryl-CoA synthase (ERG13)
  3. 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 (HMG2), 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (HMG1)
This subpathway is part of the pathway (R)-mevalonate biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-mevalonate from acetyl-CoA, the pathway (R)-mevalonate biosynthesis and in Metabolic intermediate biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei714 – 7141Charge relay systemBy similarity
Active sitei848 – 8481Charge relay systemBy similarity
Active sitei924 – 9241Charge relay systemBy similarity
Active sitei1020 – 10201Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

  • hydroxymethylglutaryl-CoA reductase (NADPH) activity Source: SGD
  • NADP binding Source: InterPro

GO - Biological processi

  • coenzyme A metabolic process Source: InterPro
  • ergosterol biosynthetic process Source: SGD
  • isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-649.
YEAST:YML075C-MONOMER.
BRENDAi1.1.1.34. 984.
ReactomeiR-SCE-191273. Cholesterol biosynthesis.
UniPathwayiUPA00058; UER00103.

Names & Taxonomyi

Protein namesi
Recommended name:
3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (EC:1.1.1.34)
Short name:
HMG-CoA reductase 1
Gene namesi
Name:HMG1
Ordered Locus Names:YML075C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XIII

Organism-specific databases

EuPathDBiFungiDB:YML075C.
SGDiS000004540. HMG1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2828CytoplasmicBy similarityAdd
BLAST
Transmembranei29 – 4921HelicalSequence analysisAdd
BLAST
Topological domaini50 – 187138LumenalBy similarityAdd
BLAST
Transmembranei188 – 20821HelicalSequence analysisAdd
BLAST
Topological domaini209 – 2179CytoplasmicBy similarity
Transmembranei218 – 23821HelicalSequence analysisAdd
BLAST
Topological domaini239 – 2468LumenalBy similarity
Transmembranei247 – 26721HelicalSequence analysisAdd
BLAST
Topological domaini268 – 30942CytoplasmicBy similarityAdd
BLAST
Transmembranei310 – 33021HelicalSequence analysisAdd
BLAST
Topological domaini331 – 3366LumenalBy similarity
Transmembranei337 – 35721HelicalSequence analysisAdd
BLAST
Topological domaini358 – 40043CytoplasmicBy similarityAdd
BLAST
Transmembranei401 – 42121HelicalSequence analysisAdd
BLAST
Topological domaini422 – 49877LumenalBy similarityAdd
BLAST
Transmembranei499 – 51921HelicalSequence analysisAdd
BLAST
Topological domaini520 – 1054535CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: SGD
  • integral component of membrane Source: UniProtKB-KW
  • nuclear envelope Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 105410543-hydroxy-3-methylglutaryl-coenzyme A reductase 1PRO_0000114456Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence analysis
Glycosylationi181 – 1811N-linked (GlcNAc...)Sequence analysis
Glycosylationi452 – 4521N-linked (GlcNAc...)Sequence analysis
Glycosylationi490 – 4901N-linked (GlcNAc...)Sequence analysis
Modified residuei552 – 5521PhosphothreonineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP12683.
PeptideAtlasiP12683.

PTM databases

iPTMnetiP12683.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
HMG2P126843EBI-8377,EBI-8384

Protein-protein interaction databases

BioGridi35066. 114 interactions.
DIPiDIP-4529N.
IntActiP12683. 32 interactions.
MINTiMINT-516133.

Structurei

3D structure databases

ProteinModelPortaliP12683.
SMRiP12683. Positions 600-1015.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini189 – 357169SSDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni525 – 61793LinkerAdd
BLAST
Regioni618 – 1054437CatalyticAdd
BLAST

Sequence similaritiesi

Belongs to the HMG-CoA reductase family.Curated
Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00840000129910.
HOGENOMiHOG000183489.
InParanoidiP12683.
KOiK00021.
OMAiNAARIHT.
OrthoDBiEOG7W41NR.

Family and domain databases

Gene3Di1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProiIPR025583. HMG-CoA_N_dom.
IPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10572. PTHR10572. 2 hits.
PfamiPF00368. HMG-CoA_red. 1 hit.
PF13323. HPIH. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiPS00066. HMG_COA_REDUCTASE_1. 1 hit.
PS00318. HMG_COA_REDUCTASE_2. 1 hit.
PS01192. HMG_COA_REDUCTASE_3. 1 hit.
PS50065. HMG_COA_REDUCTASE_4. 1 hit.
PS50156. SSD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P12683-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPLFKGLKQ MAKPIAYVSR FSAKRPIHII LFSLIISAFA YLSVIQYYFN
60 70 80 90 100
GWQLDSNSVF ETAPNKDSNT LFQECSHYYR DSSLDGWVSI TAHEASELPA
110 120 130 140 150
PHHYYLLNLN FNSPNETDSI PELANTVFEK DNTKYILQED LSVSKEISST
160 170 180 190 200
DGTKWRLRSD RKSLFDVKTL AYSLYDVFSE NVTQADPFDV LIMVTAYLMM
210 220 230 240 250
FYTIFGLFND MRKTGSNFWL SASTVVNSAS SLFLALYVTQ CILGKEVSAL
260 270 280 290 300
TLFEGLPFIV VVVGFKHKIK IAQYALEKFE RVGLSKRITT DEIVFESVSE
310 320 330 340 350
EGGRLIQDHL LCIFAFIGCS MYAHQLKTLT NFCILSAFIL IFELILTPTF
360 370 380 390 400
YSAILALRLE MNVIHRSTII KQTLEEDGVV PSTARIISKA EKKSVSSFLN
410 420 430 440 450
LSVVVIIMKL SVILLFVFIN FYNFGANWVN DAFNSLYFDK ERVSLPDFIT
460 470 480 490 500
SNASENFKEQ AIVSVTPLLY YKPIKSYQRI EDMVLLLLRN VSVAIRDRFV
510 520 530 540 550
SKLVLSALVC SAVINVYLLN AARIHTSYTA DQLVKTEVTK KSFTAPVQKA
560 570 580 590 600
STPVLTNKTV ISGSKVKSLS SAQSSSSGPS SSSEEDDSRD IESLDKKIRP
610 620 630 640 650
LEELEALLSS GNTKQLKNKE VAALVIHGKL PLYALEKKLG DTTRAVAVRR
660 670 680 690 700
KALSILAEAP VLASDRLPYK NYDYDRVFGA CCENVIGYMP LPVGVIGPLV
710 720 730 740 750
IDGTSYHIPM ATTEGCLVAS AMRGCKAINA GGGATTVLTK DGMTRGPVVR
760 770 780 790 800
FPTLKRSGAC KIWLDSEEGQ NAIKKAFNST SRFARLQHIQ TCLAGDLLFM
810 820 830 840 850
RFRTTTGDAM GMNMISKGVE YSLKQMVEEY GWEDMEVVSV SGNYCTDKKP
860 870 880 890 900
AAINWIEGRG KSVVAEATIP GDVVRKVLKS DVSALVELNI AKNLVGSAMA
910 920 930 940 950
GSVGGFNAHA ANLVTAVFLA LGQDPAQNVE SSNCITLMKE VDGDLRISVS
960 970 980 990 1000
MPSIEVGTIG GGTVLEPQGA MLDLLGVRGP HATAPGTNAR QLARIVACAV
1010 1020 1030 1040 1050
LAGELSLCAA LAAGHLVQSH MTHNRKPAEP TKPNNLDATD INRLKDGSVT

CIKS
Length:1,054
Mass (Da):115,626
Last modified:October 1, 1989 - v1
Checksum:i2B624944FB7B2DD0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22002 Genomic DNA. Translation: AAA34676.1.
Z46373 Genomic DNA. Translation: CAA86503.1.
BK006946 Genomic DNA. Translation: DAA09822.1.
PIRiA30239.
RefSeqiNP_013636.1. NM_001182434.1.

Genome annotation databases

EnsemblFungiiYML075C; YML075C; YML075C.
GeneIDi854900.
KEGGisce:YML075C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22002 Genomic DNA. Translation: AAA34676.1.
Z46373 Genomic DNA. Translation: CAA86503.1.
BK006946 Genomic DNA. Translation: DAA09822.1.
PIRiA30239.
RefSeqiNP_013636.1. NM_001182434.1.

3D structure databases

ProteinModelPortaliP12683.
SMRiP12683. Positions 600-1015.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi35066. 114 interactions.
DIPiDIP-4529N.
IntActiP12683. 32 interactions.
MINTiMINT-516133.

PTM databases

iPTMnetiP12683.

Proteomic databases

MaxQBiP12683.
PeptideAtlasiP12683.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYML075C; YML075C; YML075C.
GeneIDi854900.
KEGGisce:YML075C.

Organism-specific databases

EuPathDBiFungiDB:YML075C.
SGDiS000004540. HMG1.

Phylogenomic databases

GeneTreeiENSGT00840000129910.
HOGENOMiHOG000183489.
InParanoidiP12683.
KOiK00021.
OMAiNAARIHT.
OrthoDBiEOG7W41NR.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00103.
BioCyciMetaCyc:MONOMER-649.
YEAST:YML075C-MONOMER.
BRENDAi1.1.1.34. 984.
ReactomeiR-SCE-191273. Cholesterol biosynthesis.

Miscellaneous databases

PROiP12683.

Family and domain databases

Gene3Di1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProiIPR025583. HMG-CoA_N_dom.
IPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10572. PTHR10572. 2 hits.
PfamiPF00368. HMG-CoA_red. 1 hit.
PF13323. HPIH. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiPS00066. HMG_COA_REDUCTASE_1. 1 hit.
PS00318. HMG_COA_REDUCTASE_2. 1 hit.
PS01192. HMG_COA_REDUCTASE_3. 1 hit.
PS50065. HMG_COA_REDUCTASE_4. 1 hit.
PS50156. SSD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis."
    Basson M.E., Thorsness M., Finer-Moore J., Stroud R.M., Rine J.
    Mol. Cell. Biol. 8:3797-3808(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  4. "Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase."
    Basson M.E., Thorsness M., Rine J.
    Proc. Natl. Acad. Sci. U.S.A. 83:5563-5567(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 776-965, FUNCTION.
  5. "Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations."
    Koning A.J., Roberts C.J., Wright R.L.
    Mol. Biol. Cell 7:769-789(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  6. "Effects of overproduction of the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase on squalene synthesis in Saccharomyces cerevisiae."
    Donald K.A., Hampton R.Y., Fritz I.B.
    Appl. Environ. Microbiol. 63:3341-3344(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
  8. "Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae."
    Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P.
    J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-552, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Strain: ADR376.
  9. "Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
    Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
    Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiHMDH1_YEAST
AccessioniPrimary (citable) accession number: P12683
Secondary accession number(s): D6W0K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: June 8, 2016
This is version 171 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XIII
    Yeast (Saccharomyces cerevisiae) chromosome XIII: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.