HMCS1_RAT
ID HMCS1_RAT Reviewed; 520 AA.
AC P17425;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase, cytoplasmic {ECO:0000305};
DE Short=HMG-CoA synthase {ECO:0000250|UniProtKB:Q01581};
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:Q01581};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=Hmgcs1 {ECO:0000312|RGD:70970}; Synonyms=Hmgcs;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1972979; DOI=10.1093/nar/18.12.3642;
RA Ayte J., Gil-Gomez G., Hegardt F.G.;
RT "Nucleotide sequence of a rat liver cDNA encoding the cytosolic 3-hydroxy-
RT 3-methylglutaryl coenzyme A synthase.";
RL Nucleic Acids Res. 18:3642-3642(1990).
RN [2]
RP PROTEIN SEQUENCE OF 90-100; 220-231; 278-289; 292-305; 370-387 AND 401-409,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
CC -!- FUNCTION: Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA
CC to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into
CC mevalonate, a precursor for cholesterol synthesis.
CC {ECO:0000250|UniProtKB:P13704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-
CC methylglutaryl-CoA + CoA + H(+); Xref=Rhea:RHEA:10188,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.10;
CC Evidence={ECO:0000250|UniProtKB:Q01581};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000250|UniProtKB:Q01581};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q01581}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13704}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X52625; CAA36852.1; -; mRNA.
DR PIR; S12736; S12736.
DR RefSeq; NP_058964.1; NM_017268.1.
DR RefSeq; XP_006232021.1; XM_006231959.2.
DR AlphaFoldDB; P17425; -.
DR SMR; P17425; -.
DR IntAct; P17425; 2.
DR STRING; 10116.ENSRNOP00000023554; -.
DR BindingDB; P17425; -.
DR ChEMBL; CHEMBL2189; -.
DR GuidetoPHARMACOLOGY; 638; -.
DR iPTMnet; P17425; -.
DR PhosphoSitePlus; P17425; -.
DR SwissPalm; P17425; -.
DR jPOST; P17425; -.
DR PaxDb; P17425; -.
DR PRIDE; P17425; -.
DR Ensembl; ENSRNOT00000023554; ENSRNOP00000023554; ENSRNOG00000016552.
DR GeneID; 29637; -.
DR KEGG; rno:29637; -.
DR CTD; 3157; -.
DR RGD; 70970; Hmgcs1.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; P17425; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 495111at2759; -.
DR PhylomeDB; P17425; -.
DR TreeFam; TF105361; -.
DR BRENDA; 2.3.3.10; 5301.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00058; UER00102.
DR PRO; PR:P17425; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000016552; Expressed in liver and 20 other tissues.
DR Genevisible; P17425; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IDA:RGD.
DR GO; GO:0016853; F:isomerase activity; IDA:RGD.
DR GO; GO:0043177; F:organic acid binding; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0036094; F:small molecule binding; IDA:RGD.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0071397; P:cellular response to cholesterol; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IDA:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0070723; P:response to cholesterol; IEP:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0009645; P:response to low light intensity stimulus; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0014074; P:response to purine-containing compound; IDA:RGD.
DR GO; GO:0046690; P:response to tellurium ion; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR000590; HMG_CoA_synt_AS.
DR InterPro; IPR013746; HMG_CoA_synt_C_dom.
DR InterPro; IPR013528; HMG_CoA_synth_N.
DR InterPro; IPR010122; HMG_CoA_synthase_euk.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF08540; HMG_CoA_synt_C; 1.
DR Pfam; PF01154; HMG_CoA_synt_N; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01833; HMG-CoA-S_euk; 1.
DR PROSITE; PS01226; HMG_COA_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Direct protein sequencing; Lipid biosynthesis; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..520
FT /note="Hydroxymethylglutaryl-CoA synthase, cytoplasmic"
FT /id="PRO_0000213750"
FT REGION 487..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 95
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 129
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 264
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT BINDING 44..46
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 167
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 221
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 269
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 273
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 46
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 273
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
SQ SEQUENCE 520 AA; 57434 MW; CB213A27B0C177CB CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQARMGFCT
DREDINSLCL TVVQKLMERN SLSYDCIGRL EVGTETIIDK SKSVKSNLMQ LFEESGNTDI
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AIYASGNARP TGGVGAVALL
IGPNAPVIFD RGLRGTHMQH AYDFYKPDML SEYPVVDGKL SIQCYLSALD RCYSVYRKKI
RAQWQKEGKD KDFTLNDFGF MIFHSPYCKL VQKSLARMFL NDFLNDQNRD KNSIYSGLEA
FGDVKLEDTY FDRDVEKAFM KASAELFNQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY
SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTCVAP
DVFAENMKLR EDTHHLANYI PQCSIDSLFE GTWYLVRVDE KHRRTYARRP STNDHSLDEG
VGLVHSNTAT EHIPSPAKKV PRLPATSGEP ESAVISNGEH
