ID A0A2K6ML17_RHIBE Unreviewed; 520 AA.
AC A0A2K6ML17;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 31.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000256|RuleBase:RU364071};
DE Short=HMG-CoA synthase {ECO:0000256|RuleBase:RU364071};
DE EC=2.3.3.10 {ECO:0000256|RuleBase:RU364071};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000256|RuleBase:RU364071};
GN Name=HMGCS1 {ECO:0000313|Ensembl:ENSRBIP00000036461.1};
OS Rhinopithecus bieti (Black snub-nosed monkey) (Pygathrix bieti).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Colobinae; Rhinopithecus.
OX NCBI_TaxID=61621 {ECO:0000313|Ensembl:ENSRBIP00000036461.1, ECO:0000313|Proteomes:UP000233180};
RN [1] {ECO:0000313|Ensembl:ENSRBIP00000036461.1, ECO:0000313|Proteomes:UP000233180}
RP NUCLEOTIDE SEQUENCE.
RA Wu, C.-I. and Zhang, Y.;
RT "Genome of Rhinopithecus bieti.";
RL Submitted (JUN-2016) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSRBIP00000036461.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
CC -!- FUNCTION: Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA
CC to form HMG-CoA. {ECO:0000256|RuleBase:RU364071}.
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:0000256|ARBA:ARBA00001222};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000256|ARBA:ARBA00001222};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC {ECO:0000256|ARBA:ARBA00005218, ECO:0000256|RuleBase:RU364071}.
CC -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000256|ARBA:ARBA00007061, ECO:0000256|RuleBase:RU364071}.
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DR RefSeq; XP_017751474.1; XM_017895985.1.
DR RefSeq; XP_017751475.1; XM_017895986.1.
DR AlphaFoldDB; A0A2K6ML17; -.
DR STRING; 61621.ENSRBIP00000036461; -.
DR Ensembl; ENSRBIT00000060467.1; ENSRBIP00000036461.1; ENSRBIG00000041838.1.
DR GeneID; 108544735; -.
DR KEGG; rbb:108544735; -.
DR CTD; 3157; -.
DR GeneTree; ENSGT00390000006096; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 1060at2759; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000233180; Unplaced.
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; IEA:Ensembl.
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 CDD; cd00827; init_cond_enzymes; 1.
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 NCBIfam; TIGR01833; HMG-CoA-S_euk; 1.
DR PANTHER; PTHR43323; 3-HYDROXY-3-METHYLGLUTARYL COENZYME A SYNTHASE; 1.
DR PANTHER; PTHR43323:SF4; HYDROXYMETHYLGLUTARYL-COA SYNTHASE, CYTOPLASMIC; 1.
DR Pfam; PF08540; HMG_CoA_synt_C; 1.
DR Pfam; PF01154; HMG_CoA_synt_N; 1.
DR SUPFAM; SSF53901; Thiolase-like; 2.
DR PROSITE; PS01226; HMG_COA_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Cholesterol biosynthesis {ECO:0000256|ARBA:ARBA00022778};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022548};
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516,
KW ECO:0000256|RuleBase:RU364071};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098,
KW ECO:0000256|RuleBase:RU364071};
KW Reference proteome {ECO:0000313|Proteomes:UP000233180};
KW Steroid biosynthesis {ECO:0000256|ARBA:ARBA00022955,
KW ECO:0000256|RuleBase:RU364071};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221,
KW ECO:0000256|RuleBase:RU364071};
KW Sterol biosynthesis {ECO:0000256|ARBA:ARBA00023011,
KW ECO:0000256|RuleBase:RU364071};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166,
KW ECO:0000256|RuleBase:RU364071};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU364071}.
FT DOMAIN 13..186
FT /note="Hydroxymethylglutaryl-coenzyme A synthase N-
FT terminal"
FT /evidence="ECO:0000259|Pfam:PF01154"
FT DOMAIN 187..469
FT /note="Hydroxymethylglutaryl-coenzyme A synthase C-
FT terminal"
FT /evidence="ECO:0000259|Pfam:PF08540"
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:0000256|PIRSR:PIRSR610122-1"
FT ACT_SITE 129
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-1"
FT ACT_SITE 264
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-1"
FT BINDING 167
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 221
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 269
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 273
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
SQ SEQUENCE 520 AA; 57403 MW; 2E1AF497BC97A6B0 CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQAKMGFCT
DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK SKSVKTNLMQ LFEESGNTDI
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVIAGDI AVYATGNARP TGGVGAVALL
IGPNAPLIFE RGLRGTHMQH AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYCKKI
RAQWQKEGND KDFTLNDFGF MIFHSPYCKL VQKSLARMLL NDFLNDQNRD KNSIYSGLEA
FGDVKLEDTY FDRDVEKAFM KASSELFSQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY
SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTCVAP
DVFTENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP IPNDDTLDEG
VGLVHSNTAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH
//
