HMCS1_PONAB
ID HMCS1_PONAB Reviewed; 520 AA.
AC Q5R7Z9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
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:0000250|UniProtKB:Q01581};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=HMGCS1 {ECO:0000250|UniProtKB:Q01581};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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DR EMBL; CR859957; CAH92111.1; -; mRNA.
DR RefSeq; NP_001127508.1; NM_001134036.1.
DR RefSeq; XP_009238962.1; XM_009240687.1.
DR AlphaFoldDB; Q5R7Z9; -.
DR SMR; Q5R7Z9; -.
DR STRING; 9601.ENSPPYP00000017251; -.
DR PRIDE; Q5R7Z9; -.
DR Ensembl; ENSPPYT00000041679; ENSPPYP00000032698; ENSPPYG00000015439.
DR GeneID; 100174584; -.
DR KEGG; pon:100174584; -.
DR CTD; 3157; -.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; Q5R7Z9; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 495111at2759; -.
DR TreeFam; TF105361; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000001595; Chromosome 5.
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 2: Evidence at transcript level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Lipid biosynthesis; Lipid metabolism; Phosphoprotein; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..520
FT /note="Hydroxymethylglutaryl-CoA synthase, cytoplasmic"
FT /id="PRO_0000213749"
FT REGION 492..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 476
FT /note="Phosphothreonine"
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; 57269 MW; 0FEFBFD029D0654D CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVAAGKYTIG LGQAKMGFCT
DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK SKSVKTNLMQ LFEESGNTDI
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI 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 RLDSRTGVAP
DVFAENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP TPNDDTLDEG
VGLVHSNIAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH
