P22791 (HMCS2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Subcellular location	Mitochondrion.
Tissue specificity	Liver and kidney.
Sequence similarities	Belongs to the HMG-CoA synthase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Mitochondrion
Domain	Transit peptide
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adipose tissue development Inferred from expression pattern. Source: RGD brain development Inferred from expression pattern. Source: RGD cellular response to amino acid stimulus Inferred from expression pattern. Source: RGD cellular response to fatty acid Inferred from expression pattern. Source: RGD cellular response to glucocorticoid stimulus Inferred from expression pattern. Source: RGD cellular response to insulin stimulus Inferred from expression pattern. Source: RGD cellular response to lipopolysaccharide Inferred from expression pattern. Source: RGD cellular response to organic cyclic compound Inferred from expression pattern. 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. Source: RGD kidney development Inferred from expression pattern. Source: RGD liver development Inferred from expression pattern. Source: RGD lung development Inferred from expression pattern. Source: RGD midgut development Inferred from expression pattern. Source: RGD multicellular organismal response to stress Inferred from expression pattern. Source: RGD response to cAMP Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to ethanol Inferred from expression pattern. Source: RGD response to glucagon stimulus Inferred from expression pattern. Source: RGD response to growth hormone stimulus Inferred from expression pattern. Source: RGD response to linoleic acid Inferred from expression pattern. Source: RGD response to metal ion Inferred from expression pattern. Source: RGD response to monosaccharide stimulus Inferred from expression pattern. Source: RGD response to nutrient Inferred from expression pattern. Source: RGD response to prostaglandin F stimulus Inferred from expression pattern. Source: RGD response to starvation Inferred from expression pattern. Source: RGD response to temperature stimulus Inferred from expression pattern. Source: RGD response to testosterone stimulus Inferred from expression pattern. Source: RGD response to triglyceride Inferred from expression pattern. Source: RGD
Cellular component	mitochondrial matrix Inferred from direct assay. Source: RGD
Molecular function	hydroxymethylglutaryl-CoA synthase activity Inferred from direct assay Ref.1. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 37	37	Mitochondrion Probable
	Chain	38 – 508	471	Hydroxymethylglutaryl-CoA synthase, mitochondrial		PRO_0000013486
Sites
	Active site	166	1	Potential
Amino acid modifications
	Modified residue	83	1	N6-acetyllysine By similarity
	Modified residue	427	1	N6-acetyllysine By similarity
	Modified residue	433	1	Phosphoserine By similarity
	Modified residue	437	1	N6-acetyllysine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P22791 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: EC37693A5541D47E	FASTA	508	56,912
	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

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: 1971108] [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: 8097464] [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.
IPI	IPI00210444.
PIR	A35865.
RefSeq	NP_775117.1. NM_173094.1.
UniGene	Rn.29594.
3D structure databases
ProteinModelPortal	P22791.
SMR	P22791. Positions 53-507.
ModBase	Search...
Protein-protein interaction databases
STRING	P22791.
Proteomic databases
PRIDE	P22791.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24450.
KEGG	rno:24450.
Organism-specific databases
CTD	3158.
RGD	2804. Hmgcs2.
Phylogenomic databases
eggNOG	roNOG14554.
HOVERGEN	HBG051912.
InParanoid	P22791.
OrthoDB	EOG4H72B9.
PhylomeDB	P22791.
Enzyme and pathway databases
BRENDA	2.3.3.10. 5301.
Gene expression databases
ArrayExpress	P22791.
Genevestigator	P22791.
GermOnline	ENSRNOG00000019120. Rattus norvegicus.
Family and domain databases
InterPro	IPR000590. 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]
Gene3D	G3DSA:3.40.47.10. Thiolase-like_subgr. 1 hit.
KO	K01641.
Pfam	PF08540. HMG_CoA_synt_C. 1 hit. PF01154. HMG_CoA_synt_N. 1 hit. [Graphical view]
SUPFAM	SSF53901. Thiolase-like. 2 hits.
TIGRFAMs	TIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITE	PS01226. HMG_COA_SYNTHASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	603355.

Entry information

Entry name

HMCS2_RAT

Accession

Primary (citable) accession number: P22791

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	November 16, 2011
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program