ID A0A2K5DM47_AOTNA Unreviewed; 495 AA.
AC A0A2K5DM47;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 25.
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=HMGCS2 {ECO:0000313|Ensembl:ENSANAP00000022056.1};
OS Aotus nancymaae (Ma's night monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Aotidae;
OC Aotus.
OX NCBI_TaxID=37293 {ECO:0000313|Ensembl:ENSANAP00000022056.1, ECO:0000313|Proteomes:UP000233020};
RN [1] {ECO:0000313|Ensembl:ENSANAP00000022056.1}
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 -!- FUNCTION: Catalyzes the first irreversible step in ketogenesis,
CC condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is
CC converted by HMG-CoA reductase (HMGCR) into mevalonate.
CC {ECO:0000256|ARBA:ARBA00037714}.
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: Mitochondrion {ECO:0000256|ARBA:ARBA00004173}.
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 AlphaFoldDB; A0A2K5DM47; -.
DR Ensembl; ENSANAT00000039949.1; ENSANAP00000022056.1; ENSANAG00000028816.1.
DR GeneTree; ENSGT00390000006096; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000233020; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:UniProtKB-EC.
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:SF1; HYDROXYMETHYLGLUTARYL-COA SYNTHASE, MITOCHONDRIAL; 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 Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Cholesterol biosynthesis {ECO:0000256|ARBA:ARBA00022778};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022548};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516,
KW ECO:0000256|RuleBase:RU364071};
KW Lipid metabolism {ECO:0000256|RuleBase:RU364071};
KW Mitochondrion {ECO:0000256|ARBA:ARBA00023128};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Reference proteome {ECO:0000313|Proteomes:UP000233020};
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};
KW Transit peptide {ECO:0000256|ARBA:ARBA00022946}.
FT DOMAIN 81..196
FT /note="Hydroxymethylglutaryl-coenzyme A synthase N-
FT terminal"
FT /evidence="ECO:0000259|Pfam:PF01154"
FT DOMAIN 198..466
FT /note="Hydroxymethylglutaryl-coenzyme A synthase C-
FT terminal"
FT /evidence="ECO:0000259|Pfam:PF08540"
FT ACT_SITE 105
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-1"
FT ACT_SITE 139
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-1"
FT ACT_SITE 274
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-1"
FT BINDING 177
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 231
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 279
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
FT BINDING 283
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000256|PIRSR:PIRSR610122-2"
SQ SEQUENCE 495 AA; 55040 MW; 8286EC61722A1FDA CRC64;
MQRLLTPAKR ILQLTRVMQD ASLMPARLLP AAHQRFSTVS AVPLARTDTW PKDVGVLALE
VYFPAQYVDQ TDLEKYNNVE AVVQRLMERT QLPWDSVGRL EVGTETIIDK SKAVKTVLME
LFQDSGNTDI EGIDTTNACY GGTASLFNAA NWMESSSWDG RYAMVVCGDI AVYPNGNARP
TGGAGAVAML IGPKAPLALE QGLRGTHMEN VYDFYKPNLA SEYPVVDGKL SIQCYLRALD
RCYTSYRQKI QNQWKQAGND RPFTLDDLQY MIFHTPFCKM VQKSLARLMF NDFLSASRDT
QSNLYKGLEA FRGLKLEDTY NNKDLDKALL KASQDTFDKK TKASLYLSTH NGNMYTSSLY
GCLASLLSHH SAQELAGSRI GAFSYGSGLA ASFFSFRVSQ DASPGSPLDK LVSSTSDLPK
RLASRKCVSP EEFTEIMNQR EQFYHKVNFS PPGDTSSLFP GTWYLTVGQP IAKLRPASGL
EMFCRSVERL LGNAC
//
