HMCSA_DICDI
ID HMCSA_DICDI Reviewed; 482 AA.
AC P54872; Q54IW3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 25-MAY-2022, entry version 122.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase A;
DE Short=HMG-CoA synthase A;
DE EC=2.3.3.10;
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase A;
GN Name=hgsA; ORFNames=DDB_G0288461;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP PROTEIN SEQUENCE OF 96-104; 263-276; 300-321 AND 390-400, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=AX2;
RA Bienvenut W.V., Ura S., Insall R.H.;
RL Submitted (JUL-2009) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 304-482.
RA Dhar M.S., Hauser L.J., Olins D.E., Olins A.L.;
RT "A putative partial cDNA clone of HMG-CoA synthase from Dictyostelium
RT discoideum.";
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA,
CC which is the substrate for HMG-CoA reductase. {ECO:0000250}.
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 -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA91055.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AAFI02000111; EAL63202.1; -; Genomic_DNA.
DR EMBL; L24114; AAA91055.1; ALT_FRAME; mRNA.
DR RefSeq; XP_636713.1; XM_631621.1.
DR AlphaFoldDB; P54872; -.
DR SMR; P54872; -.
DR STRING; 44689.DDB0219924; -.
DR PaxDb; P54872; -.
DR EnsemblProtists; EAL63202; EAL63202; DDB_G0288461.
DR GeneID; 8626645; -.
DR KEGG; ddi:DDB_G0288461; -.
DR dictyBase; DDB_G0288461; hgsA.
DR eggNOG; KOG1393; Eukaryota.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; P54872; -.
DR OMA; DDAYNWI; -.
DR PhylomeDB; P54872; -.
DR Reactome; R-DDI-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00058; UER00102.
DR PRO; PR:P54872; -.
DR Proteomes; UP000002195; Chromosome 5.
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:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.47.10; -; 1.
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.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Lipid biosynthesis; Lipid metabolism;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..482
FT /note="Hydroxymethylglutaryl-CoA synthase A"
FT /id="PRO_0000213755"
FT ACT_SITE 85
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 119
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 249
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT CONFLICT 304..306
FT /note="ITK -> RHE (in Ref. 3; AAA91055)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="N -> K (in Ref. 3; AAA91055)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="Y -> F (in Ref. 3; AAA91055)"
FT /evidence="ECO:0000305"
FT CONFLICT 461..466
FT /note="QSTIKS -> HQQSNL (in Ref. 3; AAA91055)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 482 AA; 53741 MW; E6A00A6064B765AF CRC64;
MTKPENIGIH GIEVYFPSTY VAQEDLEKFD GVSQGKYTLG LGQTNMAFCG DREDIYSLSL
NAVNNLMDKF NVDPNSIGRL EVGTETVIDK SKSVKTVLMD LFAKHGNTSI DGIDTINACY
GGTSALHNAL QWMESSYWDG RNAIVVAGDI AVYEKGPARP TGGAGVVAML IGPNAPITFE
SGLRGVHMEN VYDFYKPDMD SEYPRVDGKL SISCYFRAID NCYNRYAKAF EKKYGKSFSL
DQVDFALFHS PYNKLVQKSF GRMLYNDFLN NPNDSRYASL EAYKNVKPED TYFDSVLEKA
LSAITKNDYA TKVAPTTLLA KQLGNTYCGS TYSGLLSLLD EKSNDLVGKR VLTFSYGSGL
AASAFSFKVE KPINHIVEKV DLKNRLAKRV RVEPEIFTEK LSLRETRHNL KNYVPSDETT
NMFPGSFYLS SVDNAGIRKY DRTYSTSAVL GAFQRRQQIS QSTIKSLNLF RATKSVLSIL
KK