HMCS2_BOVIN
ID HMCS2_BOVIN Reviewed; 508 AA.
AC Q2KIE6;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 105.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP SUCCINYLATION AT LYS-310.
RX PubMed=22076378; DOI=10.1126/science.1207861;
RA Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J.,
RA Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J.,
RA Hao Q., Lin H.;
RT "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.";
RL Science 334:806-809(2011).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC112666; AAI12667.1; -; mRNA.
DR RefSeq; NP_001039348.1; NM_001045883.1.
DR RefSeq; XP_010801406.1; XM_010803104.2.
DR AlphaFoldDB; Q2KIE6; -.
DR SMR; Q2KIE6; -.
DR STRING; 9913.ENSBTAP00000005088; -.
DR PaxDb; Q2KIE6; -.
DR PeptideAtlas; Q2KIE6; -.
DR PRIDE; Q2KIE6; -.
DR Ensembl; ENSBTAT00000005088; ENSBTAP00000005088; ENSBTAG00000003898.
DR GeneID; 503684; -.
DR KEGG; bta:503684; -.
DR CTD; 3158; -.
DR VEuPathDB; HostDB:ENSBTAG00000003898; -.
DR VGNC; VGNC:29881; HMGCS2.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; Q2KIE6; -.
DR OMA; YFAFHAP; -.
DR OrthoDB; 495111at2759; -.
DR TreeFam; TF105361; -.
DR Reactome; R-BTA-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000003898; Expressed in digestive system secreted substance and 49 other tissues.
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 GO; GO:0046951; P:ketone body biosynthetic process; IEA:Ensembl.
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 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_0000236276"
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:0000269|PubMed:22076378"
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 447
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
FT MOD_RES 447
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54869"
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"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22791"
SQ SEQUENCE 508 AA; 56895 MW; 12F31AAFBAE986BF CRC64;
MQRLLTPVRQ VLQVKRVMQE ASLLPARLLP AAHPSFSTVP AVPLAKTDTW PKDVGILAME
VYFPAQYVDQ TELEKFNKVE AGRYTVGLGQ TQMGFCSVQE DVNSLCLTVV QQLMERTQLP
WDSVGRLEVG TETIIDKSKA VKTVLMELFQ DSGNTDIEGI DTTNACYGGT ASLFNAANWM
ESSSWDGRYA LVVCGDIAVY PSGNARPTGG AGAVAMLVGP EAPLVLERGL RGTHMENVYD
FYKPDVTSEY PLVDGKLSIQ CYLRALDKCY AFYRQKIEKQ WKQAGIDRPF TLDDVQYMIF
HTPFCKLVQK SLARLMFNDF LLASGDTQTG IYKGLEAFRG LKLEDTYTNK DVDKAFLKAS
LNMFNKKTKN SLYLSTYNGN MYTSSLYGCL ASLLAHHSAQ DLAGSRIGAF SYGSGLAASF
FSFRVSQDAS PGSPLEKLVS STSDLQKRLA SRKRVSPEEF TEIMNQREQY YHKMNFSPPG
DKNSLFPGTW YLERVDELYR RKYARRPV
