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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

Miscellaneous

Present with 149 molecules/cell in log phase SD medium.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)DescriptionActionsGraphical viewLength
Active sitei710Charge relay systemBy similarity1
Active sitei844Charge relay systemBy similarity1
Active sitei920Charge relay systemBy similarity1
Active sitei1016Proton donorPROSITE-ProRule annotation1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processLipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism
LigandNADP

Enzyme and pathway databases

BioCyciMetaCyc:YLR450W-MONOMER.
YEAST:YLR450W-MONOMER.
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

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 24CytoplasmicSequence analysisAdd BLAST24
Transmembranei25 – 45HelicalSequence analysisAdd BLAST21
Topological domaini46 – 186LumenalSequence analysisAdd BLAST141
Transmembranei187 – 207HelicalSequence analysisAdd BLAST21
Topological domaini208 – 216CytoplasmicSequence analysis9
Transmembranei217 – 237HelicalSequence analysisAdd BLAST21
Topological domaini238 – 243LumenalSequence analysis6
Transmembranei244 – 264HelicalSequence analysisAdd BLAST21
Topological domaini265 – 301CytoplasmicSequence analysisAdd BLAST37
Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
Topological domaini323 – 324LumenalSequence analysis2
Transmembranei325 – 345HelicalSequence analysisAdd BLAST21
Topological domaini346 – 402CytoplasmicSequence analysisAdd BLAST57
Transmembranei403 – 423HelicalSequence analysisAdd BLAST21
Topological domaini424 – 497LumenalSequence analysisAdd BLAST74
Transmembranei498 – 518HelicalSequence analysisAdd BLAST21
Topological domaini519 – 1045CytoplasmicSequence analysisAdd BLAST527

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001144571 – 10453-hydroxy-3-methylglutaryl-coenzyme A reductase 2Add BLAST1045

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi150N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi158N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi428N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi455N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei565PhosphothreonineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP12684.
PRIDEiP12684.

PTM databases

iPTMnetiP12684.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi31708. 128 interactors.
DIPiDIP-6277N.
IntActiP12684. 33 interactors.
MINTiMINT-597113.
STRINGi4932.YLR450W.

Structurei

3D structure databases

ProteinModelPortaliP12684.
SMRiP12684.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini188 – 356SSDPROSITE-ProRule annotationAdd BLAST169

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni524 – 613LinkerAdd BLAST90
Regioni614 – 1045CatalyticAdd BLAST432

Sequence similaritiesi

Belongs to the HMG-CoA reductase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00840000131602.
HOGENOMiHOG000183489.
InParanoidiP12684.
KOiK00021.
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. 1 hit.
InterProiView protein in InterPro
IPR025583. HMG-CoA_N_dom.
IPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat_sf.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd_sf.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom_sf.
IPR000731. SSD.
PANTHERiPTHR10572. PTHR10572. 1 hit.
PfamiView protein in Pfam
PF00368. HMG-CoA_red. 1 hit.
PF13323. HPIH. 1 hit.
PF12349. Sterol-sensing. 1 hit.
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiView protein in PROSITE
PS00066. 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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti29V → A in AAT92819 (PubMed:17322287).Curated1

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.

Similar proteinsi

Entry informationi

Entry nameiHMDH2_YEAST
AccessioniPrimary (citable) accession number: P12684
Secondary accession number(s): D6VZ84, E9P8X3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 22, 2017
This is version 178 of the entry and version 1 of the sequence. See 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 XII
    Yeast (Saccharomyces cerevisiae) chromosome XII: entries and gene names