HMCS1_MOUSE
ID HMCS1_MOUSE Reviewed; 520 AA.
AC Q8JZK9; Q3UXI4;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase, cytoplasmic {ECO:0000305};
DE Short=HMG-CoA synthase {ECO:0000250|UniProtKB:Q01581};
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:Q01581};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=Hmgcs1 {ECO:0000312|MGI:MGI:107592};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Muellerian duct, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N, and FVB/N-3; TISSUE=Eye, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 47-75; 90-100; 220-231; 278-289; 292-313; 322-330;
RP 370-409; 416-428 AND 469-498, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA
CC to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into
CC mevalonate, a precursor for cholesterol synthesis.
CC {ECO:0000250|UniProtKB:P13704}.
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:Q01581};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000250|UniProtKB:Q01581};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q01581}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13704}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; BC023851; AAH23851.1; -; mRNA.
DR EMBL; BC029693; AAH29693.1; -; mRNA.
DR EMBL; BC034317; AAH34317.1; -; mRNA.
DR EMBL; AK031297; BAC27338.1; -; mRNA.
DR EMBL; AK044835; BAC32112.1; -; mRNA.
DR EMBL; AK045094; BAC32218.1; -; mRNA.
DR EMBL; AK135551; BAE22579.1; -; mRNA.
DR CCDS; CCDS56901.1; -.
DR RefSeq; NP_001278368.1; NM_001291439.1.
DR RefSeq; NP_666054.2; NM_145942.5.
DR RefSeq; XP_006517641.1; XM_006517578.1.
DR AlphaFoldDB; Q8JZK9; -.
DR SMR; Q8JZK9; -.
DR BioGRID; 229007; 6.
DR STRING; 10090.ENSMUSP00000136944; -.
DR iPTMnet; Q8JZK9; -.
DR PhosphoSitePlus; Q8JZK9; -.
DR SwissPalm; Q8JZK9; -.
DR REPRODUCTION-2DPAGE; Q8JZK9; -.
DR EPD; Q8JZK9; -.
DR jPOST; Q8JZK9; -.
DR MaxQB; Q8JZK9; -.
DR PaxDb; Q8JZK9; -.
DR PRIDE; Q8JZK9; -.
DR ProteomicsDB; 269603; -.
DR Antibodypedia; 23240; 252 antibodies from 32 providers.
DR DNASU; 208715; -.
DR Ensembl; ENSMUST00000179869; ENSMUSP00000136944; ENSMUSG00000093930.
DR Ensembl; ENSMUST00000224188; ENSMUSP00000153064; ENSMUSG00000093930.
DR GeneID; 208715; -.
DR KEGG; mmu:208715; -.
DR UCSC; uc007rzv.2; mouse.
DR CTD; 3157; -.
DR MGI; MGI:107592; Hmgcs1.
DR VEuPathDB; HostDB:ENSMUSG00000093930; -.
DR eggNOG; KOG1393; Eukaryota.
DR GeneTree; ENSGT00390000006096; -.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; Q8JZK9; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 495111at2759; -.
DR PhylomeDB; Q8JZK9; -.
DR TreeFam; TF105361; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00058; UER00102.
DR BioGRID-ORCS; 208715; 27 hits in 73 CRISPR screens.
DR ChiTaRS; Hmgcs1; mouse.
DR PRO; PR:Q8JZK9; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8JZK9; protein.
DR Bgee; ENSMUSG00000093930; Expressed in metanephric proximal tubule and 260 other tissues.
DR ExpressionAtlas; Q8JZK9; baseline and differential.
DR Genevisible; Q8JZK9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; ISO:MGI.
DR GO; GO:0016853; F:isomerase activity; ISO:MGI.
DR GO; GO:0043177; F:organic acid binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0036094; F:small molecule binding; ISO:MGI.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:MGI.
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:0014074; P:response to purine-containing compound; ISO:MGI.
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; Cytoplasm;
KW Direct protein sequencing; Lipid biosynthesis; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..520
FT /note="Hydroxymethylglutaryl-CoA synthase, cytoplasmic"
FT /id="PRO_0000213748"
FT REGION 488..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 95
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 129
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 264
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT BINDING 44..46
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 167
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 221
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 269
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT BINDING 273
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 46
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 273
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01581"
SQ SEQUENCE 520 AA; 57569 MW; E28F8772CF64D85C CRC64;
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQARMGFCT
DREDINSLCL TVVQKLMERH SLSYDCIGRL EVGTETIIDK SKSVKSNLMQ LFEESGNTDI
EGIDTTNACY GGTAAVFNAV NWVESSSWDG RYALVVAGDI AIYATGNARP TGGVGAVALL
IGPNAPLIFD RGLRGTHMQH AYDFYKPDML SEYPVVDGKL SIQCYLSALD RCYSVYRKKI
RAQWQKEGKD KDFTLNDFGF MIFHSPYCKL VQKSLARMFL NDFLNDQNRD KNSIYSGLEA
FGDVKLEDTY FDRDVEKAFM KASSELFNQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY
SPQQLAGKRV GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTCVAP
DVFAENMKLR EDTHHLANYI PQCSIDSLFE GTWYLVRVDE KHRRTYARRP FTNDHSLDEG
MGLVHSNTAT EHIPSPAKKV PRLPATSAES ESAVISNGEH
