HMCS2_PIG
ID HMCS2_PIG Reviewed; 508 AA.
AC O02734; A5GFY7;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase, mitochondrial;
DE Short=HMG-CoA synthase;
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:P54868};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
DE Flags: Precursor;
GN Name=HMGCS2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=9164842; DOI=10.1042/bj3240065;
RA Adams S.H., Alho C.S., Asins G., Hegardt F.G., Marrero P.F.;
RT "Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase
RT in a poorly ketogenic mammal: effect of starvation during the neonatal
RT period of the piglet.";
RL Biochem. J. 324:65-73(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:P54868}.
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:P54868};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000250|UniProtKB:P54868};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P54868}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P22791}.
CC -!- PTM: Succinylated. Desuccinylated by SIRT5. Succinylation, at least at
CC Lys-310, inhibits the enzymatic activity.
CC {ECO:0000250|UniProtKB:P54869}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; U90884; AAC48727.1; -; mRNA.
DR EMBL; CR956647; CAN13229.1; -; Genomic_DNA.
DR RefSeq; NP_999545.1; NM_214380.2.
DR AlphaFoldDB; O02734; -.
DR SMR; O02734; -.
DR STRING; 9823.ENSSSCP00000007162; -.
DR PaxDb; O02734; -.
DR PeptideAtlas; O02734; -.
DR PRIDE; O02734; -.
DR Ensembl; ENSSSCT00000007357; ENSSSCP00000007162; ENSSSCG00000036808.
DR Ensembl; ENSSSCT00000064945; ENSSSCP00000042638; ENSSSCG00000036808.
DR Ensembl; ENSSSCT00000065031; ENSSSCP00000046688; ENSSSCG00000036808.
DR Ensembl; ENSSSCT00000065128; ENSSSCP00000055613; ENSSSCG00000036808.
DR Ensembl; ENSSSCT00015043748; ENSSSCP00015017272; ENSSSCG00015032911.
DR Ensembl; ENSSSCT00015043925; ENSSSCP00015017363; ENSSSCG00015032911.
DR Ensembl; ENSSSCT00070005881; ENSSSCP00070004797; ENSSSCG00070003102.
DR GeneID; 397673; -.
DR KEGG; ssc:397673; -.
DR CTD; 3158; -.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; O02734; -.
DR OrthoDB; 495111at2759; -.
DR TreeFam; TF105361; -.
DR BRENDA; 2.3.3.10; 6170.
DR Reactome; R-SSC-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000008227; Chromosome 4.
DR Proteomes; UP000314985; Chromosome 4.
DR Bgee; ENSSSCG00000036808; Expressed in right lobe of liver and 10 other tissues.
DR ExpressionAtlas; O02734; baseline.
DR Genevisible; O02734; SS.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; Phosphoprotein;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase; Transit peptide.
FT TRANSIT 1..37
FT /note="Mitochondrion"
FT /evidence="ECO:0000305"
FT CHAIN 38..508
FT /note="Hydroxymethylglutaryl-CoA synthase, mitochondrial"
FT /id="PRO_0000013485"
FT ACT_SITE 132
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 166
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 301
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT BINDING 80
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT BINDING 258
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT BINDING 380
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT MOD_RES 52
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 256
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 256
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 306
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 310
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 310
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q2KIE6"
FT MOD_RES 333
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 342
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 342
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 350
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 350
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 354
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 354
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 358
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 358
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT MOD_RES 437
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54868"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 473
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 473
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
SQ SEQUENCE 508 AA; 56934 MW; 5479DE6F70B3C0F6 CRC64;
MQRLLTPVRQ VLRVKRAMQE ASFMPPLLPP AAHQRFSTVP AVPVAKADTW PKDVGILALE
VYFPAQYVDQ TDLEKFDNVE AGRYTVGLGQ THMGFCSVQE DINSLCLTVV QRLMERTQLP
WDSVGWLEVG TETIIDKSKS VKTVLMELFQ DSGNTDIEGI DTTNACYGGT ASLFNAANWV
ESSAWDGRYA VVVCGDIAVY PRGNSRPTGG AGAVAMLVGP EAPLALERGL RGTHMENAYD
FYKPNATSEY PLVDGKLSIQ CYLRALDRCY TLYRQKIEKQ WKQAGIERHF TLDDLQFMIF
HTPFCKLVQK SLARLMFSDF LLADSDTQSS LYKGLEAFRG QKLEDTYANK DIEKAFQKAS
LDLFNKKTKP SLYLSLHNGN MYTSSLYGCL ASLLSQCSAQ DLAGSRIGAF SYGSGLAASF
YSLRVSQDAS PGSPLEKLVS SVSDLPERLA SRKRVSPEEF TEIMNQREQY YHKVNFTPPG
DPNSLFPGTW YLERVDELYR RKYARHLV
