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Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

Hmgcs2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

Catalytic activityi

Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.PROSITE-ProRule annotation

Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 2 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. no protein annotated in this organism
  2. Hydroxymethylglutaryl-CoA synthase, mitochondrial (Hmgcs2), Hydroxymethylglutaryl-CoA synthase, cytoplasmic (Hmgcs1)
  3. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr)
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
Binding sitei80SubstrateBy similarity1
Active sitei132Proton donor/acceptorPROSITE-ProRule annotation1
Active sitei166Acyl-thioester intermediatePROSITE-ProRule annotation1
Binding sitei204SubstrateBy similarity1
Binding sitei258SubstrateBy similarity1
Active sitei301Proton donor/acceptorPROSITE-ProRule annotation1
Binding sitei380SubstrateBy similarity1

GO - Molecular functioni

  • hydroxymethylglutaryl-CoA synthase activity Source: RGD

GO - Biological processi

  • adipose tissue development Source: RGD
  • brain development Source: RGD
  • cellular response to amino acid stimulus Source: RGD
  • cellular response to fatty acid Source: RGD
  • cellular response to glucocorticoid stimulus Source: RGD
  • cellular response to hormone stimulus Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • cellular response to lipopolysaccharide Source: RGD
  • cellular response to organic cyclic compound Source: RGD
  • cholesterol biosynthetic process Source: UniProtKB-KW
  • isoprenoid biosynthetic process Source: InterPro
  • ketone body biosynthetic process Source: RGD
  • kidney development Source: RGD
  • liver development Source: RGD
  • lung development Source: RGD
  • midgut development Source: RGD
  • multicellular organismal response to stress Source: RGD
  • response to bacterium Source: RGD
  • response to cAMP Source: RGD
  • response to drug Source: RGD
  • response to ethanol Source: RGD
  • response to fatty acid Source: RGD
  • response to glucagon Source: RGD
  • response to glucocorticoid Source: RGD
  • response to growth hormone Source: RGD
  • response to insulin Source: RGD
  • response to linoleic acid Source: RGD
  • response to metal ion Source: RGD
  • response to monosaccharide Source: RGD
  • response to nutrient Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to peptide hormone Source: RGD
  • response to prostaglandin F Source: RGD
  • response to starvation Source: RGD
  • response to temperature stimulus Source: RGD
  • response to testosterone Source: RGD
  • response to triglyceride Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

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

Enzyme and pathway databases

BRENDAi2.3.3.10. 5301.
UniPathwayiUPA00058; UER00102.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.10)
Short name:
HMG-CoA synthase
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene namesi
Name:Hmgcs2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2804. Hmgcs2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: RGD
  • mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 37MitochondrionCuratedAdd BLAST37
ChainiPRO_000001348638 – 508Hydroxymethylglutaryl-CoA synthase, mitochondrialAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52N6-succinyllysineBy similarity1
Modified residuei83N6-acetyllysine; alternateBy similarity1
Modified residuei83N6-succinyllysine; alternateBy similarity1
Modified residuei118N6-acetyllysine; alternateBy similarity1
Modified residuei118N6-succinyllysine; alternateBy similarity1
Modified residuei221N6-succinyllysineBy similarity1
Modified residuei243N6-acetyllysineBy similarity1
Modified residuei256N6-acetyllysine; alternateBy similarity1
Modified residuei256N6-succinyllysine; alternateBy similarity1
Modified residuei306N6-acetyllysineBy similarity1
Modified residuei310N6-acetyllysine; alternateBy similarity1
Modified residuei310N6-succinyllysine; alternateBy similarity1
Modified residuei327N6-acetyllysine; alternateBy similarity1
Modified residuei327N6-succinyllysine; alternateBy similarity1
Modified residuei333N6-succinyllysineBy similarity1
Modified residuei342N6-acetyllysine; alternateBy similarity1
Modified residuei342N6-succinyllysine; alternateBy similarity1
Modified residuei350N6-acetyllysine; alternateBy similarity1
Modified residuei350N6-succinyllysine; alternateBy similarity1
Modified residuei354N6-acetyllysine; alternateBy similarity1
Modified residuei354N6-succinyllysine; alternateBy similarity1
Modified residuei358N6-acetyllysine; alternateBy similarity1
Modified residuei358N6-succinyllysine; alternateBy similarity1
Modified residuei427N6-acetyllysineBy similarity1
Modified residuei433PhosphoserineBy similarity1
Modified residuei437N6-acetyllysineBy similarity1
Modified residuei440PhosphoserineCombined sources1
Modified residuei447N6-acetyllysine; alternateBy similarity1
Modified residuei447N6-succinyllysine; alternateBy similarity1
Modified residuei456PhosphoserineBy similarity1
Modified residuei473N6-acetyllysine; alternateBy similarity1
Modified residuei473N6-succinyllysine; alternateBy similarity1
Modified residuei477PhosphoserineCombined sources1

Post-translational modificationi

Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP22791.
PRIDEiP22791.

PTM databases

iPTMnetiP22791.
PhosphoSitePlusiP22791.
SwissPalmiP22791.

Expressioni

Tissue specificityi

Liver and kidney.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026122.

Structurei

3D structure databases

ProteinModelPortaliP22791.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiP22791.
PhylomeDBiP22791.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22791-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRLLAPARR VLQVKRVMQE SSLSPAHLLP AAQQRFSTIP PAPLAKTDTW
60 70 80 90 100
PKDVGILALE VYFPAQYVDQ TDLEKFNNVE AGKYTVGLGQ TRMGFCSVQE
110 120 130 140 150
DINSLCLTVV QRLMERTKLP WDAVGRLEVG TETIIDKSKA VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSYWDGRYA LVVCGDIAVY
210 220 230 240 250
PSGNPRPTGG AGAVAMLIGP KAPLVLEQGL RGTHMENAYD FYKPNLASEY
260 270 280 290 300
PLVDGKLSIQ CYLRALDRCY AAYRRKIQNQ WKQAGNNQPF TLDDVQYMIF
310 320 330 340 350
HTPFCKMVQK SLARLMFNDF LSSSSDKQNN LYKGLEAFKG LKLEETYTNK
360 370 380 390 400
DVDKALLKAS LDMFNKKTKA SLYLSTNNGN MYTSSLYGCL ASLLSHHSAQ
410 420 430 440 450
ELAGSRIGAF SYGSGLAASF FSFRVSKDAS PGSPLEKLVS SVSDLPKRLD
460 470 480 490 500
SRRRMSPEEF TEIMNQREQF YHKVNFSPPG DTSNLFPGTW YLERVDEMHR

RKYARRPV
Length:508
Mass (Da):56,912
Last modified:August 1, 1991 - v1
Checksum:iEC37693A5541D47E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33648 mRNA. Translation: AAA41336.1.
M63800 Genomic DNA. No translation available.
PIRiA35865.
UniGeneiRn.29594.

Genome annotation databases

UCSCiRGD:2804. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33648 mRNA. Translation: AAA41336.1.
M63800 Genomic DNA. No translation available.
PIRiA35865.
UniGeneiRn.29594.

3D structure databases

ProteinModelPortaliP22791.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026122.

PTM databases

iPTMnetiP22791.
PhosphoSitePlusiP22791.
SwissPalmiP22791.

Proteomic databases

PaxDbiP22791.
PRIDEiP22791.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2804. rat.

Organism-specific databases

RGDi2804. Hmgcs2.

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiP22791.
PhylomeDBiP22791.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BRENDAi2.3.3.10. 5301.

Miscellaneous databases

PROiP22791.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHMCS2_RAT
AccessioniPrimary (citable) accession number: P22791
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 2, 2016
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata 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

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.