HMCS1_CRIGR
ID HMCS1_CRIGR Reviewed; 520 AA.
AC P13704;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase, cytoplasmic {ECO:0000250|UniProtKB:Q01581};
DE Short=HMG-CoA synthase {ECO:0000250|UniProtKB:Q01581};
DE EC=2.3.3.10 {ECO:0000269|PubMed:2869035};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=HMGCS1 {ECO:0000250|UniProtKB:Q01581}; Synonyms=HMGCS;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RC TISSUE=Ovary;
RX PubMed=2869035; DOI=10.1016/s0021-9258(17)35705-8;
RA Gil G., Goldstein J.L., Slaughter C.A., Brown M.S.;
RT "Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase from the
RT hamster. I. Isolation and sequencing of a full-length cDNA.";
RL J. Biol. Chem. 261:3710-3716(1986).
CC -!- FUNCTION: This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form
CC HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into
CC mevalonate, a precursor for cholesterol synthesis.
CC {ECO:0000269|PubMed:2869035}.
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:0000269|PubMed:2869035};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000305|PubMed:2869035};
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:0000269|PubMed:2869035}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; L00334; AAA37076.1; -; Genomic_DNA.
DR EMBL; L00326; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00327; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00328; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00329; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00330; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00331; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00332; AAA37076.1; JOINED; Genomic_DNA.
DR EMBL; L00333; AAA37076.1; JOINED; Genomic_DNA.
DR PIR; A25332; A25332.
DR AlphaFoldDB; P13704; -.
DR SMR; P13704; -.
DR STRING; 10029.XP_007632907.1; -.
DR eggNOG; KOG1393; Eukaryota.
DR BRENDA; 2.3.3.10; 1309.
DR UniPathway; UPA00058; UER00102.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IEA:InterPro.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IEA:InterPro.
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 Lipid biosynthesis; Lipid metabolism; Phosphoprotein; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..520
FT /note="Hydroxymethylglutaryl-CoA synthase, cytoplasmic"
FT /id="PRO_0000213746"
FT REGION 486..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; 57318 MW; 2D4CAAE7DEE5D6BB CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQARMGFCT
DREDINSLCL TVVQNLMERN SLSYDCIGRL EVGTETIIDK SKSVKSNLMQ LFEESGNTDI
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AIYATGNARP TGGVGAVALL
IGPNAPLIFD RGLRGTHMQH AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYRKKI
RAQWQKEGND NDFTLNDFGF MISHSPYCKL VQKSLARMFL NDFLNDQNRD KNSIYSGLEA
FGDVKLEDTY FDRDVEKAFM KASSELFNQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY
SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK VTASLCDLKS RLDSRTCVAP
DVFAENMKLR EDTHHLANYI PQCSIDSLFE GTWYLVRVDE KHRRTYARRP STNDHNLGDG
VGLVHSNTAT EHIPSPAKKV PRLPATAAES ESAVISNGEH
