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   24-JAN-2024, entry version 172.
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; 7.
DR   IntAct; Q8JZK9; 1.
DR   STRING; 10090.ENSMUSP00000153064; -.
DR   GlyGen; Q8JZK9; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; Q8JZK9; -.
DR   PhosphoSitePlus; Q8JZK9; -.
DR   SwissPalm; Q8JZK9; -.
DR   REPRODUCTION-2DPAGE; Q8JZK9; -.
DR   EPD; Q8JZK9; -.
DR   jPOST; Q8JZK9; -.
DR   MaxQB; Q8JZK9; -.
DR   PaxDb; 10090-ENSMUSP00000136944; -.
DR   ProteomicsDB; 269603; -.
DR   Pumba; Q8JZK9; -.
DR   Antibodypedia; 23240; 272 antibodies from 32 providers.
DR   DNASU; 208715; -.
DR   Ensembl; ENSMUST00000179869.3; ENSMUSP00000136944.2; ENSMUSG00000093930.3.
DR   Ensembl; ENSMUST00000224188.2; ENSMUSP00000153064.2; ENSMUSG00000093930.3.
DR   GeneID; 208715; -.
DR   KEGG; mmu:208715; -.
DR   UCSC; uc007rzv.2; mouse.
DR   AGR; MGI:107592; -.
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; 1060at2759; -.
DR   PhylomeDB; Q8JZK9; -.
DR   TreeFam; TF105361; -.
DR   Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR   UniPathway; UPA00058; UER00102.
DR   BioGRID-ORCS; 208715; 27 hits in 78 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 264 other cell types or tissues.
DR   ExpressionAtlas; Q8JZK9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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   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.
DR   Genevisible; Q8JZK9; MM.
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
//