ID F7HQ90_MACMU Unreviewed; 520 AA.
AC F7HQ90;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 27-JUL-2011, sequence version 1.
DT 27-MAR-2024, entry version 75.
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|EMBL:AFH32183.1,
GN ECO:0000313|Ensembl:ENSMMUP00000034768.1,
GN ECO:0000313|VGNC:VGNC:73485};
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544 {ECO:0000313|Ensembl:ENSMMUP00000034768.1, ECO:0000313|Proteomes:UP000006718};
RN [1] {ECO:0000313|Proteomes:UP000006718}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17573 {ECO:0000313|Proteomes:UP000006718};
RX PubMed=17431167; DOI=10.1126/science.1139247;
RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M.,
RA Mardis E.R., Remington K.A., Strausberg R.L., Venter J.C., Wilson R.K.,
RA Batzer M.A., Bustamante C.D., Eichler E.E., Hahn M.W., Hardison R.C.,
RA Makova K.D., Miller W., Milosavljevic A., Palermo R.E., Siepel A.,
RA Sikela J.M., Attaway T., Bell S., Bernard K.E., Buhay C.J.,
RA Chandrabose M.N., Dao M., Davis C., Delehaunty K.D., Ding Y., Dinh H.H.,
RA Dugan-Rocha S., Fulton L.A., Gabisi R.A., Garner T.T., Godfrey J.,
RA Hawes A.C., Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N.,
RA Joshi V., Khan Z.M., Kirkness E.F., Cree A., Fowler R.G., Lee S.,
RA Lewis L.R., Li Z., Liu Y.-S., Moore S.M., Muzny D., Nazareth L.V.,
RA Ngo D.N., Okwuonu G.O., Pai G., Parker D., Paul H.A., Pfannkoch C.,
RA Pohl C.S., Rogers Y.-H.C., Ruiz S.J., Sabo A., Santibanez J.,
RA Schneider B.W., Smith S.M., Sodergren E., Svatek A.F., Utterback T.R.,
RA Vattathil S., Warren W., White C.S., Chinwalla A.T., Feng Y., Halpern A.L.,
RA Hillier L.W., Huang X., Minx P., Nelson J.O., Pepin K.H., Qin X.,
RA Sutton G.G., Venter E., Walenz B.P., Wallis J.W., Worley K.C., Yang S.-P.,
RA Jones S.M., Marra M.A., Rocchi M., Schein J.E., Baertsch R., Clarke L.,
RA Csuros M., Glasscock J., Harris R.A., Havlak P., Jackson A.R., Jiang H.,
RA Liu Y., Messina D.N., Shen Y., Song H.X.-Z., Wylie T., Zhang L., Birney E.,
RA Han K., Konkel M.K., Lee J., Smit A.F.A., Ullmer B., Wang H., Xing J.,
RA Burhans R., Cheng Z., Karro J.E., Ma J., Raney B., She X., Cox M.J.,
RA Demuth J.P., Dumas L.J., Han S.-G., Hopkins J., Karimpour-Fard A.,
RA Kim Y.H., Pollack J.R., Vinar T., Addo-Quaye C., Degenhardt J., Denby A.,
RA Hubisz M.J., Indap A., Kosiol C., Lahn B.T., Lawson H.A., Marklein A.,
RA Nielsen R., Vallender E.J., Clark A.G., Ferguson B., Hernandez R.D.,
RA Hirani K., Kehrer-Sawatzki H., Kolb J., Patil S., Pu L.-L., Ren Y.,
RA Smith D.G., Wheeler D.A., Schenck I., Ball E.V., Chen R., Cooper D.N.,
RA Giardine B., Hsu F., Kent W.J., Lesk A., Nelson D.L., O'brien W.E.,
RA Pruefer K., Stenson P.D., Wallace J.C., Ke H., Liu X.-M., Wang P.,
RA Xiang A.P., Yang F., Barber G.P., Haussler D., Karolchik D., Kern A.D.,
RA Kuhn R.M., Smith K.E., Zwieg A.S.;
RT "Evolutionary and biomedical insights from the rhesus macaque genome.";
RL Science 316:222-234(2007).
RN [2] {ECO:0000313|EMBL:AFH32183.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Testis {ECO:0000313|EMBL:AFI35548.1}, and Thymus
RC {ECO:0000313|EMBL:AFH32183.1};
RX PubMed=25319552; DOI=10.1186/1745-6150-9-20;
RA Zimin A.V., Cornish A.S., Maudhoo M.D., Gibbs R.M., Zhang X., Pandey S.,
RA Meehan D.T., Wipfler K., Bosinger S.E., Johnson Z.P., Tharp G.K.,
RA Marcais G., Roberts M., Ferguson B., Fox H.S., Treangen T., Salzberg S.L.,
RA Yorke J.A., Norgren R.B.Jr.;
RT "A new rhesus macaque assembly and annotation for next-generation
RT sequencing analyses.";
RL Biol. Direct 9:20-20(2014).
RN [3] {ECO:0000313|Ensembl:ENSMMUP00000034768.1}
RP IDENTIFICATION.
RC STRAIN=17573 {ECO:0000313|Ensembl:ENSMMUP00000034768.1};
RG Ensembl;
RL Submitted (NOV-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 EMBL; JU475379; AFH32183.1; -; mRNA.
DR EMBL; JV045477; AFI35548.1; -; mRNA.
DR EMBL; JV045478; AFI35549.1; -; mRNA.
DR RefSeq; NP_001247798.1; NM_001260869.1.
DR RefSeq; XP_014995459.1; XM_015139973.1.
DR RefSeq; XP_014995460.1; XM_015139974.1.
DR RefSeq; XP_014995461.1; XM_015139975.1.
DR STRING; 9544.ENSMMUP00000062864; -.
DR PaxDb; 9544-ENSMMUP00000001641; -.
DR Ensembl; ENSMMUT00000041755.3; ENSMMUP00000034768.1; ENSMMUG00000001226.4.
DR Ensembl; ENSMMUT00000097092.1; ENSMMUP00000062864.1; ENSMMUG00000001226.4.
DR Ensembl; ENSMMUT00000105116.1; ENSMMUP00000069992.1; ENSMMUG00000001226.4.
DR GeneID; 702553; -.
DR KEGG; mcc:702553; -.
DR CTD; 3157; -.
DR VEuPathDB; HostDB:ENSMMUG00000001226; -.
DR VGNC; VGNC:73485; HMGCS1.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 1060at2759; -.
DR TreeFam; TF105361; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000006718; Chromosome 6.
DR Bgee; ENSMMUG00000001226; Expressed in colon and 22 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
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 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 2: Evidence at transcript level;
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:UP000006718};
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; 57347 MW; 6B9FB8C0B7DD4B99 CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG 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 RLDSRTCVAP
DVFAENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP TPNDDTLDEG
VGLVHSNTAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH
//
