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Protein

3-hydroxy-3-methylglutaryl-coenzyme A reductase 2

Gene

HMG2

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.1 Publication

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 sitei710 – 7101Charge relay systemBy similarity
Active sitei844 – 8441Charge relay systemBy similarity
Active sitei920 – 9201Charge relay systemBy similarity
Active sitei1016 – 10161Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

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-650.
YEAST:YLR450W-MONOMER.
ReactomeiR-SCE-191273. Cholesterol biosynthesis.
UniPathwayiUPA00058; UER00103.

Names & Taxonomyi

Protein namesi
Recommended name:
3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 (EC:1.1.1.34)
Short name:
HMG-CoA reductase 2
Gene namesi
Name:HMG2
Ordered Locus Names:YLR450W
ORF Names:L9324.2
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XII

Organism-specific databases

EuPathDBiFungiDB:YLR450W.
SGDiS000004442. HMG2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2424CytoplasmicSequence analysisAdd
BLAST
Transmembranei25 – 4521HelicalSequence analysisAdd
BLAST
Topological domaini46 – 186141LumenalSequence analysisAdd
BLAST
Transmembranei187 – 20721HelicalSequence analysisAdd
BLAST
Topological domaini208 – 2169CytoplasmicSequence analysis
Transmembranei217 – 23721HelicalSequence analysisAdd
BLAST
Topological domaini238 – 2436LumenalSequence analysis
Transmembranei244 – 26421HelicalSequence analysisAdd
BLAST
Topological domaini265 – 30137CytoplasmicSequence analysisAdd
BLAST
Transmembranei302 – 32221HelicalSequence analysisAdd
BLAST
Topological domaini323 – 3242LumenalSequence analysis
Transmembranei325 – 34521HelicalSequence analysisAdd
BLAST
Topological domaini346 – 40257CytoplasmicSequence analysisAdd
BLAST
Transmembranei403 – 42321HelicalSequence analysisAdd
BLAST
Topological domaini424 – 49774LumenalSequence analysisAdd
BLAST
Transmembranei498 – 51821HelicalSequence analysisAdd
BLAST
Topological domaini519 – 1045527CytoplasmicSequence analysisAdd
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 – 104510453-hydroxy-3-methylglutaryl-coenzyme A reductase 2PRO_0000114457Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence analysis
Glycosylationi150 – 1501N-linked (GlcNAc...)Sequence analysis
Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence analysis
Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence analysis
Glycosylationi428 – 4281N-linked (GlcNAc...)Sequence analysis
Glycosylationi455 – 4551N-linked (GlcNAc...)Sequence analysis
Modified residuei565 – 5651PhosphothreonineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP12684.

PTM databases

iPTMnetiP12684.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
HMG1P126833EBI-8384,EBI-8377

Protein-protein interaction databases

BioGridi31708. 64 interactions.
DIPiDIP-6277N.
IntActiP12684. 32 interactions.
MINTiMINT-597113.

Structurei

3D structure databases

ProteinModelPortaliP12684.
SMRiP12684. Positions 640-1010.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini188 – 356169SSDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni524 – 61390LinkerAdd
BLAST
Regioni614 – 1045432CatalyticAdd
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

GeneTreeiENSGT00840000131602.
HOGENOMiHOG000183489.
InParanoidiP12684.
KOiK00021.
OMAiVEINRAR.
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.

P12684-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLPLKTIVH LVKPFACTAR FSARYPIHVI VVAVLLSAAA YLSVTQSYLN
60 70 80 90 100
EWKLDSNQYS TYLSIKPDEL FEKCTHYYRS PVSDTWKLLS SKEAADIYTP
110 120 130 140 150
FHYYLSTISF QSKDNSTTLP SLDDVIYSVD HTRYLLSEEP KIPTELVSEN
160 170 180 190 200
GTKWRLRNNS NFILDLHNIY RNMVKQFSNK TSEFDQFDLF IILAAYLTLF
210 220 230 240 250
YTLCCLFNDM RKIGSKFWLS FSALSNSACA LYLSLYTTHS LLKKPASLLS
260 270 280 290 300
LVIGLPFIVV IIGFKHKVRL AAFSLQKFHR ISIDKKITVS NIIYEAMFQE
310 320 330 340 350
GAYLIRDYLF YISSFIGCAI YARHLPGLVN FCILSTFMLV FDLLLSATFY
360 370 380 390 400
SAILSMKLEI NIIHRSTVIR QTLEEDGVVP TTADIIYKDE TASEPHFLRS
410 420 430 440 450
NVAIILGKAS VIGLLLLINL YVFTDKLNAT ILNTVYFDST IYSLPNFINY
460 470 480 490 500
KDIGNLSNQV IISVLPKQYY TPLKKYHQIE DSVLLIIDSV SNAIRDQFIS
510 520 530 540 550
KLLFFAFAVS ISINVYLLNA AKIHTGYMNF QPQSNKIDDL VVQQKSATIE
560 570 580 590 600
FSETRSMPAS SGLETPVTAK DIIISEEIQN NECVYALSSQ DEPIRPLSNL
610 620 630 640 650
VELMEKEQLK NMNNTEVSNL VVNGKLPLYS LEKKLEDTTR AVLVRRKALS
660 670 680 690 700
TLAESPILVS EKLPFRNYDY DRVFGACCEN VIGYMPIPVG VIGPLIIDGT
710 720 730 740 750
SYHIPMATTE GCLVASAMRG CKAINAGGGA TTVLTKDGMT RGPVVRFPTL
760 770 780 790 800
IRSGACKIWL DSEEGQNSIK KAFNSTSRFA RLQHIQTCLA GDLLFMRFRT
810 820 830 840 850
TTGDAMGMNM ISKGVEYSLK QMVEEYGWED MEVVSVSGNY CTDKKPAAIN
860 870 880 890 900
WIEGRGKSVV AEATIPGDVV KSVLKSDVSA LVELNISKNL VGSAMAGSVG
910 920 930 940 950
GFNAHAANLV TALFLALGQD PAQNVESSNC ITLMKEVDGD LRISVSMPSI
960 970 980 990 1000
EVGTIGGGTV LEPQGAMLDL LGVRGPHPTE PGANARQLAR IIACAVLAGE
1010 1020 1030 1040
LSLCSALAAG HLVQSHMTHN RKTNKANELP QPSNKGPPCK TSALL
Length:1,045
Mass (Da):115,692
Last modified:October 1, 1989 - v1
Checksum:i1FD9DCD3AC01B15E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti29 – 291V → A in AAT92819 (PubMed:17322287).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22255 Genomic DNA. Translation: AAA34677.1.
U22382 Genomic DNA. Translation: AAB67527.1.
AY692800 Genomic DNA. Translation: AAT92819.1.
BK006945 Genomic DNA. Translation: DAA09750.1.
PIRiB30239.
RefSeqiNP_013555.1. NM_001182338.1.

Genome annotation databases

EnsemblFungiiYLR450W; YLR450W; YLR450W.
GeneIDi851171.
KEGGisce:YLR450W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22255 Genomic DNA. Translation: AAA34677.1.
U22382 Genomic DNA. Translation: AAB67527.1.
AY692800 Genomic DNA. Translation: AAT92819.1.
BK006945 Genomic DNA. Translation: DAA09750.1.
PIRiB30239.
RefSeqiNP_013555.1. NM_001182338.1.

3D structure databases

ProteinModelPortaliP12684.
SMRiP12684. Positions 640-1010.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi31708. 64 interactions.
DIPiDIP-6277N.
IntActiP12684. 32 interactions.
MINTiMINT-597113.

PTM databases

iPTMnetiP12684.

Proteomic databases

MaxQBiP12684.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYLR450W; YLR450W; YLR450W.
GeneIDi851171.
KEGGisce:YLR450W.

Organism-specific databases

EuPathDBiFungiDB:YLR450W.
SGDiS000004442. HMG2.

Phylogenomic databases

GeneTreeiENSGT00840000131602.
HOGENOMiHOG000183489.
InParanoidiP12684.
KOiK00021.
OMAiVEINRAR.
OrthoDBiEOG7W41NR.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00103.
BioCyciMetaCyc:MONOMER-650.
YEAST:YLR450W-MONOMER.
ReactomeiR-SCE-191273. Cholesterol biosynthesis.

Miscellaneous databases

NextBioi967981.
PROiP12684.

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. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."
    Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H.
    , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D.
    Nature 387:87-90(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  5. "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 772-961, FUNCTION.
  6. "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.
  7. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
  8. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  9. "A global topology map of the Saccharomyces cerevisiae membrane proteome."
    Kim H., Melen K., Oesterberg M., von Heijne G.
    Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
    Strain: ATCC 208353 / W303-1A.
  10. "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-565, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Strain: ADR376.
  11. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
    Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
    Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-565, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiHMDH2_YEAST
AccessioniPrimary (citable) accession number: P12684
Secondary accession number(s): D6VZ84, E9P8X3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: May 11, 2016
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 149 molecules/cell in log phase SD medium.1 Publication

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 XII
    Yeast (Saccharomyces cerevisiae) chromosome XII: 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.