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P22791 (HMCS2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hydroxymethylglutaryl-CoA synthase, mitochondrial

Short name=HMG-CoA synthase
EC=2.3.3.10
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene names
Name:Hmgcs2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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

Catalytic activity

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

Pathway

Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.

Subunit structure

Homodimer By similarity.

Subcellular location

Mitochondrion.

Tissue specificity

Liver and kidney.

Sequence similarities

Belongs to the HMG-CoA synthase family.

Ontologies

Keywords
   Biological processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentMitochondrion
   DomainTransit peptide
   Molecular functionTransferase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadipose tissue development

Inferred from expression pattern PubMed 10357839. Source: RGD

brain development

Inferred from expression pattern PubMed 34385. Source: RGD

cellular response to amino acid stimulus

Inferred from expression pattern PubMed 20508999. Source: RGD

cellular response to fatty acid

Inferred from expression pattern PubMed 20508999. Source: RGD

cellular response to glucocorticoid stimulus

Inferred from expression pattern PubMed 9798904. Source: RGD

cellular response to hormone stimulus

Inferred from expression pattern PubMed 9025717. Source: RGD

cellular response to insulin stimulus

Inferred from expression pattern PubMed 12027802. Source: RGD

cellular response to lipopolysaccharide

Inferred from expression pattern PubMed 11578593. Source: RGD

cellular response to organic cyclic compound

Inferred from expression pattern PubMed 7694571. Source: RGD

cholesterol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

isoprenoid biosynthetic process

Inferred from electronic annotation. Source: InterPro

ketone body biosynthetic process

Inferred from expression pattern PubMed 12399220. Source: RGD

kidney development

Inferred from expression pattern PubMed 8099282. Source: RGD

liver development

Inferred from expression pattern PubMed 8620869. Source: RGD

lung development

Inferred from expression pattern PubMed 7911291. Source: RGD

midgut development

Inferred from expression pattern PubMed 8620869. Source: RGD

multicellular organismal response to stress

Inferred from expression pattern PubMed 16962226. Source: RGD

response to bacterium

Inferred from expression pattern PubMed 14686922. Source: RGD

response to cAMP

Inferred from expression pattern PubMed 7902069. Source: RGD

response to drug

Inferred from expression pattern PubMed 11323196PubMed 15107969. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 17964421. Source: RGD

response to fatty acid

Inferred from expression pattern PubMed 10796071. Source: RGD

response to glucagon

Inferred from expression pattern PubMed 1967579. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 9546617. Source: RGD

response to growth hormone

Inferred from expression pattern PubMed 11551854. Source: RGD

response to insulin

Inferred from expression pattern PubMed 9143333. Source: RGD

response to linoleic acid

Inferred from expression pattern PubMed 16216487. Source: RGD

response to metal ion

Inferred from expression pattern PubMed 8100835. Source: RGD

response to monosaccharide

Inferred from expression pattern PubMed 1967579. Source: RGD

response to nutrient

Inferred from expression pattern PubMed 17103110. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 20137896. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 12027802. Source: RGD

response to prostaglandin F

Inferred from expression pattern PubMed 11517196. Source: RGD

response to starvation

Inferred from expression pattern PubMed 10357839. Source: RGD

response to temperature stimulus

Inferred from expression pattern PubMed 10357839. Source: RGD

response to testosterone

Inferred from expression pattern PubMed 10357839. Source: RGD

response to triglyceride

Inferred from expression pattern PubMed 11551854. Source: RGD

   Cellular_componentmitochondrial matrix

Inferred from direct assay PubMed 17971398. Source: RGD

mitochondrion

Traceable author statement Ref.2. Source: RGD

   Molecular_functionhydroxymethylglutaryl-CoA synthase activity

Inferred from direct assay Ref.1. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3737Mitochondrion Probable
Chain38 – 508471Hydroxymethylglutaryl-CoA synthase, mitochondrial
PRO_0000013486

Sites

Active site1321Proton donor/acceptor By similarity
Active site1661Nucleophile By similarity
Active site3011Proton donor/acceptor By similarity
Binding site801Substrate By similarity
Binding site2041Substrate By similarity
Binding site2581Substrate By similarity
Binding site3801Substrate By similarity

Amino acid modifications

Modified residue521N6-succinyllysine By similarity
Modified residue831N6-acetyllysine; alternate By similarity
Modified residue831N6-succinyllysine; alternate By similarity
Modified residue1181N6-acetyllysine; alternate By similarity
Modified residue1181N6-succinyllysine; alternate By similarity
Modified residue2211N6-succinyllysine By similarity
Modified residue2431N6-acetyllysine By similarity
Modified residue2561N6-acetyllysine; alternate By similarity
Modified residue2561N6-succinyllysine; alternate By similarity
Modified residue3061N6-acetyllysine By similarity
Modified residue3101N6-acetyllysine; alternate By similarity
Modified residue3101N6-succinyllysine; alternate By similarity
Modified residue3271N6-acetyllysine; alternate By similarity
Modified residue3271N6-succinyllysine; alternate By similarity
Modified residue3331N6-succinyllysine By similarity
Modified residue3421N6-acetyllysine; alternate By similarity
Modified residue3421N6-succinyllysine; alternate By similarity
Modified residue3501N6-acetyllysine; alternate By similarity
Modified residue3501N6-succinyllysine; alternate By similarity
Modified residue3541N6-acetyllysine; alternate By similarity
Modified residue3541N6-succinyllysine; alternate By similarity
Modified residue3581N6-acetyllysine; alternate By similarity
Modified residue3581N6-succinyllysine; alternate By similarity
Modified residue4271N6-acetyllysine By similarity
Modified residue4371N6-acetyllysine By similarity
Modified residue4471N6-acetyllysine; alternate By similarity
Modified residue4471N6-succinyllysine; alternate By similarity
Modified residue4731N6-acetyllysine; alternate By similarity
Modified residue4731N6-succinyllysine; alternate By similarity

Sequences

Sequence LengthMass (Da)Tools
P22791 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: EC37693A5541D47E

FASTA50856,912
        10         20         30         40         50         60 
MQRLLAPARR VLQVKRVMQE SSLSPAHLLP AAQQRFSTIP PAPLAKTDTW PKDVGILALE 

        70         80         90        100        110        120 
VYFPAQYVDQ TDLEKFNNVE AGKYTVGLGQ TRMGFCSVQE DINSLCLTVV QRLMERTKLP 

       130        140        150        160        170        180 
WDAVGRLEVG TETIIDKSKA VKTVLMELFQ DSGNTDIEGI DTTNACYGGT ASLFNAANWM 

       190        200        210        220        230        240 
ESSYWDGRYA LVVCGDIAVY PSGNPRPTGG AGAVAMLIGP KAPLVLEQGL RGTHMENAYD 

       250        260        270        280        290        300 
FYKPNLASEY PLVDGKLSIQ CYLRALDRCY AAYRRKIQNQ WKQAGNNQPF TLDDVQYMIF 

       310        320        330        340        350        360 
HTPFCKMVQK SLARLMFNDF LSSSSDKQNN LYKGLEAFKG LKLEETYTNK DVDKALLKAS 

       370        380        390        400        410        420 
LDMFNKKTKA SLYLSTNNGN MYTSSLYGCL ASLLSHHSAQ ELAGSRIGAF SYGSGLAASF 

       430        440        450        460        470        480 
FSFRVSKDAS PGSPLEKLVS SVSDLPKRLD SRRRMSPEEF TEIMNQREQF YHKVNFSPPG 

       490        500 
DTSNLFPGTW YLERVDEMHR RKYARRPV 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M33648 mRNA. Translation: AAA41336.1.
M63800 Genomic DNA. No translation available.
PIRA35865.
UniGeneRn.29594.

3D structure databases

ProteinModelPortalP22791.
SMRP22791. Positions 53-507.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000026122.

PTM databases

PhosphoSiteP22791.

Proteomic databases

PaxDbP22791.
PRIDEP22791.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2804. rat.

Organism-specific databases

RGD2804. Hmgcs2.

Phylogenomic databases

eggNOGCOG3425.
HOGENOMHOG000012351.
HOVERGENHBG051912.
InParanoidP22791.
PhylomeDBP22791.

Enzyme and pathway databases

BRENDA2.3.3.10. 5301.
UniPathwayUPA00058; UER00102.

Gene expression databases

GenevestigatorP22791.

Family and domain databases

Gene3D3.40.47.10. 1 hit.
InterProIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]
PfamPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMSSF53901. SSF53901. 3 hits.
TIGRFAMsTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio603355.
PROP22791.

Entry information

Entry nameHMCS2_RAT
AccessionPrimary (citable) accession number: P22791
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways