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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)DescriptionActionsGraphical viewLength
Active sitei714Charge relay systemBy similarity1
Active sitei848Charge relay systemBy similarity1
Active sitei924Charge relay systemBy similarity1
Active sitei1020Proton donorPROSITE-ProRule annotation1

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
  • isoprenoid biosynthetic process Source: GO_Central
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:YML075C-MONOMER.
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)DescriptionActionsGraphical viewLength
Topological domaini1 – 28CytoplasmicBy similarityAdd BLAST28
Transmembranei29 – 49HelicalSequence analysisAdd BLAST21
Topological domaini50 – 187LumenalBy similarityAdd BLAST138
Transmembranei188 – 208HelicalSequence analysisAdd BLAST21
Topological domaini209 – 217CytoplasmicBy similarity9
Transmembranei218 – 238HelicalSequence analysisAdd BLAST21
Topological domaini239 – 246LumenalBy similarity8
Transmembranei247 – 267HelicalSequence analysisAdd BLAST21
Topological domaini268 – 309CytoplasmicBy similarityAdd BLAST42
Transmembranei310 – 330HelicalSequence analysisAdd BLAST21
Topological domaini331 – 336LumenalBy similarity6
Transmembranei337 – 357HelicalSequence analysisAdd BLAST21
Topological domaini358 – 400CytoplasmicBy similarityAdd BLAST43
Transmembranei401 – 421HelicalSequence analysisAdd BLAST21
Topological domaini422 – 498LumenalBy similarityAdd BLAST77
Transmembranei499 – 519HelicalSequence analysisAdd BLAST21
Topological domaini520 – 1054CytoplasmicBy similarityAdd BLAST535

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001144561 – 10543-hydroxy-3-methylglutaryl-coenzyme A reductase 1Add BLAST1054

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115N-linked (GlcNAc...)Sequence analysis1
Glycosylationi181N-linked (GlcNAc...)Sequence analysis1
Glycosylationi452N-linked (GlcNAc...)Sequence analysis1
Glycosylationi490N-linked (GlcNAc...)Sequence analysis1
Modified residuei552PhosphothreonineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP12683.
PRIDEiP12683.

PTM databases

iPTMnetiP12683.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP12683.
SMRiP12683.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini189 – 357SSDPROSITE-ProRule annotationAdd BLAST169

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni525 – 617LinkerAdd BLAST93
Regioni618 – 1054CatalyticAdd BLAST437

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.
OrthoDBiEOG092C3BIQ.

Family and domain databases

CDDicd00643. HMG-CoA_reductase_classI. 1 hit.
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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP12683.

Proteomic databases

MaxQBiP12683.
PRIDEiP12683.

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.
OrthoDBiEOG092C3BIQ.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP12683.

Family and domain databases

CDDicd00643. HMG-CoA_reductase_classI. 1 hit.
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...

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: November 2, 2016
This is version 175 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.