HMCS1_CHICK
ID HMCS1_CHICK Reviewed; 522 AA.
AC P23228;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase, cytoplasmic;
DE Short=HMG-CoA synthase;
DE EC=2.3.3.10 {ECO:0000269|PubMed:7696316};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=HMGCS1; Synonyms=HMGCS;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1980405; DOI=10.1016/0003-9861(90)90677-q;
RA Kattar-Cooley P.A., Wang H.-H.L., Mende-Mueller L.M., Miziorko H.M.;
RT "Avian liver 3-hydroxy-3-methylglutaryl-CoA synthase: distinct genes encode
RT the cholesterogenic and ketogenic isozymes.";
RL Arch. Biochem. Biophys. 283:523-529(1990).
RN [2]
RP CHARACTERIZATION, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF CYS-59; CYS-69; CYS-224; CYS-232 AND
RP CYS-268.
RX PubMed=7696316; DOI=10.1016/0167-4838(94)00223-4;
RA Misra I., Charlier H.A. Jr., Miziorko H.M.;
RT "Avian cytosolic 3-hydroxy-3-methylglutaryl-CoA synthase: evaluation of the
RT role of cysteines in reaction chemistry.";
RL Biochim. Biophys. Acta 1247:253-259(1995).
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:0000269|PubMed:7696316}.
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:7696316};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000305|PubMed:7696316};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=294 uM for acetyl-CoA {ECO:0000269|PubMed:7696316};
CC Vmax=4.4 umol/min/mg enzyme with acetyl-CoA as substrate
CC {ECO:0000269|PubMed:7696316};
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}.
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DR EMBL; M60657; AAA62737.1; -; mRNA.
DR PIR; S13887; S13887.
DR RefSeq; NP_990742.1; NM_205411.1.
DR AlphaFoldDB; P23228; -.
DR SMR; P23228; -.
DR STRING; 9031.ENSGALP00000023936; -.
DR PaxDb; P23228; -.
DR GeneID; 396379; -.
DR KEGG; gga:396379; -.
DR CTD; 3157; -.
DR VEuPathDB; HostDB:geneid_396379; -.
DR eggNOG; KOG1393; Eukaryota.
DR InParanoid; P23228; -.
DR PhylomeDB; P23228; -.
DR BRENDA; 2.3.3.10; 1306.
DR SABIO-RK; P23228; -.
DR UniPathway; UPA00058; UER00102.
DR PRO; PR:P23228; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
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 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 Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Lipid biosynthesis; Lipid metabolism; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..522
FT /note="Hydroxymethylglutaryl-CoA synthase, cytoplasmic"
FT /id="PRO_0000213751"
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 MUTAGEN 59
FT /note="C->A: Does not affect significatively
FT biophysicochemical properties."
FT /evidence="ECO:0000269|PubMed:7696316"
FT MUTAGEN 69
FT /note="C->A: Does not affect significatively
FT biophysicochemical properties."
FT /evidence="ECO:0000269|PubMed:7696316"
FT MUTAGEN 224
FT /note="C->A: Does not affect significatively
FT biophysicochemical properties."
FT /evidence="ECO:0000269|PubMed:7696316"
FT MUTAGEN 232
FT /note="C->A: Does not affect significatively
FT biophysicochemical properties."
FT /evidence="ECO:0000269|PubMed:7696316"
FT MUTAGEN 268
FT /note="C->A: Does not affect significatively
FT biophysicochemical properties."
FT /evidence="ECO:0000269|PubMed:7696316"
SQ SEQUENCE 522 AA; 57559 MW; BFF7947C3E963C4C CRC64;
MPGSLPVNTE SCWPKDVGIV ALEIYFPSQY VDQTELEKYD GVDAGKYTIG LGQSKMGFCS
DREDINSLCL TVVQKLMERN SLSYDCIGRL EVGTETIIDK SKSVKTVLMQ LFEESGNTDV
EGIDTTNACY GGTAALFNAI NWIESSSWDG RYALVVAGDI AVYATGNARP TGGAGAVAML
VGSNAPLIFE RGLRGTHMQH AYDFYKPDMV SEYPVVDGKL SIQCYLSALD RCYSVYRNKI
HAQWQKEGTD RGFTLNDFGF MIFHSPYCKL VQKSVARLLL NDFLSDQNAE TANGVFSGLE
AFRDVKLEDT YFDRDVEKAF MKASAELFNQ KTKASLLVSN QNGNMYTPSV YGCLASLLAQ
YSPEHLAGQR ISEFSYGSGF AATLYSIRVT QDATPGSALD KITASLSDLK ARLDSRKCIA
PDVFAENMKI RQETHHLANY IPQCSVEDLF EGTWYLVRVD EKHRRTYARR PVMGDGPLEA
GVEVVHPGIV HEHIPSPAKK VPRIPATTES EGVTVAISNG VH
