P17425 (HMCS1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hydroxymethylglutaryl-CoA synthase, cytoplasmic
Short name=HMG-CoA synthase
EC=2.3.3.10

Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase

Gene names

Name:	Hmgcs1
Synonyms:	Hmgcs

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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	Cytoplasm.
Sequence similarities	Belongs to the HMG-CoA synthase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Cytoplasm
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from expression pattern PubMed 6133227. Source: RGD cellular response to cholesterol Inferred from expression pattern PubMed 18303831. Source: RGD cellular response to follicle-stimulating hormone stimulus Inferred from expression pattern PubMed 19196834. Source: RGD cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW isoprenoid biosynthetic process Inferred from electronic annotation. Source: InterPro liver development Inferred from expression pattern PubMed 5166591. Source: RGD male gonad development Inferred from expression pattern PubMed 11792726. Source: RGD response to acid Inferred from expression pattern PubMed 3670308. Source: RGD response to drug Inferred from expression pattern PubMed 16020911PubMed 17311803. Source: RGD response to lipoprotein particle stimulus Inferred from expression pattern PubMed 16260. Source: RGD response to low light intensity stimulus Inferred from expression pattern PubMed 1683769. Source: RGD response to purine-containing compound Inferred from expression pattern PubMed 16260. Source: RGD response to tellurium ion Inferred from expression pattern PubMed 10642751. Source: RGD response to vitamin E Inferred from expression pattern PubMed 15753162. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 14984735. Source: RGD nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	drug binding Inferred from direct assay PubMed 14984735. Source: RGD hydroxymethylglutaryl-CoA synthase activity Inferred from direct assay PubMed 8094614. Source: RGD isomerase activity Inferred from direct assay PubMed 17764185. Source: RGD organic acid binding Inferred from direct assay PubMed 8094614. Source: RGD protein homodimerization activity Inferred from direct assay PubMed 14984735. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Hydroxymethylglutaryl-CoA synthase, cytoplasmic		PRO_0000213750
Sites
	Active site	129	1	Potential
Amino acid modifications
	Modified residue	4	1	Phosphoserine By similarity
	Modified residue	46	1	N6-acetyllysine By similarity
	Modified residue	273	1	N6-acetyllysine By similarity
	Modified residue	495	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P17425 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: CB213A27B0C177CB	FASTA	520	57,434
	10 20 30 40 50 60 MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQARMGFCT 70 80 90 100 110 120 DREDINSLCL TVVQKLMERN SLSYDCIGRL EVGTETIIDK SKSVKSNLMQ LFEESGNTDI 130 140 150 160 170 180 EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AIYASGNARP TGGVGAVALL 190 200 210 220 230 240 IGPNAPVIFD RGLRGTHMQH AYDFYKPDML SEYPVVDGKL SIQCYLSALD RCYSVYRKKI 250 260 270 280 290 300 RAQWQKEGKD KDFTLNDFGF MIFHSPYCKL VQKSLARMFL NDFLNDQNRD KNSIYSGLEA 310 320 330 340 350 360 FGDVKLEDTY FDRDVEKAFM KASAELFNQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY 370 380 390 400 410 420 SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTCVAP 430 440 450 460 470 480 DVFAENMKLR EDTHHLANYI PQCSIDSLFE GTWYLVRVDE KHRRTYARRP STNDHSLDEG 490 500 510 520 VGLVHSNTAT EHIPSPAKKV PRLPATSGEP ESAVISNGEH

References

[1]	"Nucleotide sequence of a rat liver cDNA encoding the cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase." Ayte J., Gil-Gomez G., Hegardt F.G. Nucleic Acids Res. 18:3642-3642(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
[2]	Lubec G., Afjehi-Sadat L., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 90-100; 220-231; 278-289; 292-305; 370-387 AND 401-409, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus and Spinal cord.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52625 mRNA. Translation: CAA36852.1.
IPI	IPI00188158.
PIR	S12736.
RefSeq	NP_058964.1. NM_017268.1.
UniGene	Rn.5106.
3D structure databases
ProteinModelPortal	P17425.
SMR	P17425. Positions 16-470.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000023554.
PTM databases
PhosphoSite	P17425.
Proteomic databases
PaxDb	P17425.
PRIDE	P17425.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000023554; ENSRNOP00000023554; ENSRNOG00000016552.
GeneID	29637.
KEGG	rno:29637.
Organism-specific databases
CTD	3157.
RGD	70970. Hmgcs1.
Phylogenomic databases
eggNOG	COG3425.
GeneTree	ENSGT00390000006096.
HOGENOM	HOG000012351.
HOVERGEN	HBG051912.
InParanoid	P17425.
KO	K01641.
OMA	RDFTLND.
OrthoDB	EOG4F1X30.
Enzyme and pathway databases
BRENDA	2.3.3.10. 5301.
UniPathway	UPA00058; UER00102.
Gene expression databases
Genevestigator	P17425.
GermOnline	ENSRNOG00000016552. Rattus norvegicus.
Family and domain databases
Gene3D	3.40.47.10. 1 hit.
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]
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
BindingDB	P17425.
ChEMBL	CHEMBL2189.
NextBio	609884.

Entry information

Entry name

HMCS1_RAT

Accession

Primary (citable) accession number: P17425

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	April 3, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program