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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 transcript 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

Pathway:i(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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei80 – 801SubstrateBy similarity
Active sitei132 – 1321Proton donor/acceptorPROSITE-ProRule annotation
Active sitei166 – 1661Acyl-thioester intermediatePROSITE-ProRule annotation
Binding sitei204 – 2041SubstrateBy similarity
Binding sitei258 – 2581SubstrateBy similarity
Active sitei301 – 3011Proton donor/acceptorPROSITE-ProRule annotation
Binding sitei380 – 3801SubstrateBy similarity

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
ProteomesiUP000002494 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)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3737MitochondrionCuratedAdd
BLAST
Chaini38 – 508471Hydroxymethylglutaryl-CoA synthase, mitochondrialPRO_0000013486Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei52 – 521N6-succinyllysineBy similarity
Modified residuei83 – 831N6-acetyllysine; alternateBy similarity
Modified residuei83 – 831N6-succinyllysine; alternateBy similarity
Modified residuei118 – 1181N6-acetyllysine; alternateBy similarity
Modified residuei118 – 1181N6-succinyllysine; alternateBy similarity
Modified residuei221 – 2211N6-succinyllysineBy similarity
Modified residuei243 – 2431N6-acetyllysineBy similarity
Modified residuei256 – 2561N6-acetyllysine; alternateBy similarity
Modified residuei256 – 2561N6-succinyllysine; alternateBy similarity
Modified residuei306 – 3061N6-acetyllysineBy similarity
Modified residuei310 – 3101N6-acetyllysine; alternateBy similarity
Modified residuei310 – 3101N6-succinyllysine; alternateBy similarity
Modified residuei327 – 3271N6-acetyllysine; alternateBy similarity
Modified residuei327 – 3271N6-succinyllysine; alternateBy similarity
Modified residuei333 – 3331N6-succinyllysineBy similarity
Modified residuei342 – 3421N6-acetyllysine; alternateBy similarity
Modified residuei342 – 3421N6-succinyllysine; alternateBy similarity
Modified residuei350 – 3501N6-acetyllysine; alternateBy similarity
Modified residuei350 – 3501N6-succinyllysine; alternateBy similarity
Modified residuei354 – 3541N6-acetyllysine; alternateBy similarity
Modified residuei354 – 3541N6-succinyllysine; alternateBy similarity
Modified residuei358 – 3581N6-acetyllysine; alternateBy similarity
Modified residuei358 – 3581N6-succinyllysine; alternateBy similarity
Modified residuei427 – 4271N6-acetyllysineBy similarity
Modified residuei433 – 4331PhosphoserineBy similarity
Modified residuei437 – 4371N6-acetyllysineBy similarity
Modified residuei440 – 4401PhosphoserineBy similarity
Modified residuei447 – 4471N6-acetyllysine; alternateBy similarity
Modified residuei447 – 4471N6-succinyllysine; alternateBy similarity
Modified residuei473 – 4731N6-acetyllysine; alternateBy similarity
Modified residuei473 – 4731N6-succinyllysine; alternateBy similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP22791.
PRIDEiP22791.

PTM databases

PhosphoSiteiP22791.

Expressioni

Tissue specificityi

Liver and kidney.

Gene expression databases

GenevisibleiP22791. RN.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026122.

Structurei

3D structure databases

ProteinModelPortaliP22791.
SMRiP22791. Positions 53-507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG3425.
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.
SMRiP22791. Positions 53-507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026122.

PTM databases

PhosphoSiteiP22791.

Proteomic databases

PaxDbiP22791.
PRIDEiP22791.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2804. rat.

Organism-specific databases

RGDi2804. Hmgcs2.

Phylogenomic databases

eggNOGiCOG3425.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiP22791.
PhylomeDBiP22791.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BRENDAi2.3.3.10. 5301.

Miscellaneous databases

NextBioi603355.
PROiP22791.

Gene expression databases

GenevisibleiP22791. RN.

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...

Publicationsi

  1. "Rat mitochondrial and cytosolic 3-hydroxy-3-methylglutaryl-CoA synthases are encoded by two different genes."
    Ayte J., Gil-Gomez G., Haro D., Marrero P.F., Hegardt F.G.
    Proc. Natl. Acad. Sci. U.S.A. 87:3874-3878(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. "The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity."
    Gil-Gomez G., Ayte J., Hegardt F.G.
    Eur. J. Biochem. 213:773-779(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.

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: July 22, 2015
This is version 125 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

External Data

Dasty 3

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 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.