ID A0A0R4IQG1_DANRE Unreviewed; 519 AA.
AC A0A0R4IQG1; A0A8M2B251;
DT 20-JAN-2016, integrated into UniProtKB/TrEMBL.
DT 20-JAN-2016, sequence version 1.
DT 27-MAR-2024, entry version 49.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000256|ARBA:ARBA00012978, ECO:0000256|RuleBase:RU364071};
DE Short=HMG-CoA synthase {ECO:0000256|RuleBase:RU364071};
DE EC=2.3.3.10 {ECO:0000256|ARBA:ARBA00012978, ECO:0000256|RuleBase:RU364071};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000256|ARBA:ARBA00033130, ECO:0000256|RuleBase:RU364071};
GN Name=hmgcs1 {ECO:0000313|Ensembl:ENSDARP00000137373,
GN ECO:0000313|RefSeq:XP_005155548.1,
GN ECO:0000313|ZFIN:ZDB-GENE-040426-1042};
GN Synonyms=zgc:56481 {ECO:0000313|RefSeq:XP_005155548.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000313|Ensembl:ENSDARP00000137373};
RN [1] {ECO:0000313|Ensembl:ENSDARP00000137373, ECO:0000313|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000137373};
RX PubMed=23594743; DOI=10.1038/nature12111;
RG Genome Reference Consortium Zebrafish;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000313|Ensembl:ENSDARP00000137373}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000137373};
RG Ensembl;
RL Submitted (NOV-2015) to UniProtKB.
RN [3] {ECO:0000313|RefSeq:XP_005155548.1}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:XP_005155548.1};
RG RefSeq;
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 -!- 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; BX322605; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005155548.1; XM_005155491.3.
DR STRING; 7955.ENSDARP00000137373; -.
DR PaxDb; 7955-ENSDARP00000121903; -.
DR Ensembl; ENSDART00000167613.2; ENSDARP00000137373.1; ENSDARG00000103025.2.
DR Ensembl; ENSDART00000190025.1; ENSDARP00000145051.1; ENSDARG00000103025.2.
DR GeneID; 394060; -.
DR AGR; ZFIN:ZDB-GENE-040426-1042; -.
DR CTD; 3157; -.
DR ZFIN; ZDB-GENE-040426-1042; hmgcs1.
DR eggNOG; KOG1393; Eukaryota.
DR OMA; DDAYNWI; -.
DR OrthoDB; 1060at2759; -.
DR Reactome; R-DRE-191273; Cholesterol biosynthesis.
DR Reactome; R-DRE-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000000437; Chromosome 10.
DR Bgee; ENSDARG00000103025; Expressed in zone of skin and 36 other cell types or tissues.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IBA:GO_Central.
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:0048703; P:embryonic viscerocranium morphogenesis; IMP:ZFIN.
DR GO; GO:0048821; P:erythrocyte development; IMP:ZFIN.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0014033; P:neural crest cell differentiation; IMP:ZFIN.
DR GO; GO:0014003; P:oligodendrocyte development; IMP:ZFIN.
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:SF2; HYDROXYMETHYLGLUTARYL-COA SYNTHASE; 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 1: Evidence at protein level;
KW Cholesterol biosynthesis {ECO:0000256|ARBA:ARBA00022778};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022548};
KW Lipid biosynthesis {ECO:0000256|RuleBase:RU364071};
KW Lipid metabolism {ECO:0000256|RuleBase:RU364071};
KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A0R4IQG1};
KW Reference proteome {ECO:0000313|Proteomes:UP000000437};
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 188..470
FT /note="Hydroxymethylglutaryl-coenzyme A synthase C-
FT terminal"
FT /evidence="ECO:0000259|Pfam:PF08540"
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 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 519 AA; 57009 MW; A1355E795DD3BA48 CRC64;
MPGSLPAICE SMWPKDVGII AMEVYVPSQY VDQAELEEYD GVGAGKYTVG LGQARMGFCS
DREDINSLCL TVVQRLMERN GLSYESVGRL EVGTETIIDK SKSTKTVLMQ LFEESGNTDV
EGVDTTNACY GGTAALFNAV NWVESSSWDG RYALVVAGDI AVYATGSARP TGGAGAVAML
VGPNAPLAFE RGLRGTHMQH AYDFYKPDMV SEYPVVDGKL SIQCYLSALD QCYSVYKNKI
HARWQREGTE GRCSLEDFGF MVFHSPYCKL VQKSLARLML NDFLCHPSPN MESGPFSGLE
AFRDVKIEDT YFDRDVEKAF MKASSELFDD KTKASLLISN QNGNMYTPSV YGCLASVLAQ
HTPQQLAGQR IGVFSYGSGF AATLYSIKVT QDGTPGSALD KLVSSLCDLP ARLDSRQKVS
PGVFAETMKL REETHHLANY IPQGSVDELF PGTWYLTRVD EKHRRQYARR SMNDDRPLEA
GLVSSSMAAE HIPSPLKKMP RIPTTTAGPE VVVMSNGDH
//
