HMGC2_MOUSE
ID HMGC2_MOUSE Reviewed; 343 AA.
AC Q8JZS7;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic;
DE EC=4.1.3.4;
DE AltName: Full=3-hydroxy-3-methylglutaryl-CoA lyase-like protein 1;
GN Name=Hmgcll1;
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=Hippocampus;
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 TISSUE=Eye;
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).
CC -!- FUNCTION: Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase
CC that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-
CC methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in
CC ketogenesis, the products of which support energy production in
CC nonhepatic animal tissues. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA;
CC Xref=Rhea:RHEA:24404, ChEBI:CHEBI:13705, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57288; EC=4.1.3.4;
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3-
CC methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-
CC methylglutaryl-CoA: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Endoplasmic
CC reticulum membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
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DR EMBL; AK141622; BAE24772.1; -; mRNA.
DR EMBL; BC037381; AAH37381.1; -; mRNA.
DR CCDS; CCDS23349.1; -.
DR RefSeq; NP_776092.1; NM_173731.2.
DR AlphaFoldDB; Q8JZS7; -.
DR SMR; Q8JZS7; -.
DR STRING; 10090.ENSMUSP00000008052; -.
DR iPTMnet; Q8JZS7; -.
DR PhosphoSitePlus; Q8JZS7; -.
DR jPOST; Q8JZS7; -.
DR MaxQB; Q8JZS7; -.
DR PaxDb; Q8JZS7; -.
DR PRIDE; Q8JZS7; -.
DR ProteomicsDB; 267054; -.
DR Antibodypedia; 31030; 61 antibodies from 14 providers.
DR DNASU; 208982; -.
DR Ensembl; ENSMUST00000008052; ENSMUSP00000008052; ENSMUSG00000007908.
DR GeneID; 208982; -.
DR KEGG; mmu:208982; -.
DR UCSC; uc009qsx.1; mouse.
DR CTD; 54511; -.
DR MGI; MGI:2446108; Hmgcll1.
DR VEuPathDB; HostDB:ENSMUSG00000007908; -.
DR eggNOG; KOG2368; Eukaryota.
DR GeneTree; ENSGT00940000159467; -.
DR InParanoid; Q8JZS7; -.
DR OMA; FHNTRGT; -.
DR OrthoDB; 1029775at2759; -.
DR PhylomeDB; Q8JZS7; -.
DR TreeFam; TF105363; -.
DR Reactome; R-MMU-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00896; UER00863.
DR BioGRID-ORCS; 208982; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Hmgcll1; mouse.
DR PRO; PR:Q8JZS7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8JZS7; protein.
DR Bgee; ENSMUSG00000007908; Expressed in animal zygote and 109 other tissues.
DR ExpressionAtlas; Q8JZS7; baseline and differential.
DR Genevisible; Q8JZS7; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0046951; P:ketone body biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006552; P:leucine catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR030021; ER-cHL.
DR InterPro; IPR043594; HMGL.
DR InterPro; IPR000891; PYR_CT.
DR PANTHER; PTHR42738; PTHR42738; 1.
DR PANTHER; PTHR42738:SF5; PTHR42738:SF5; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Endoplasmic reticulum; Lipid metabolism; Lipoprotein; Lyase;
KW Membrane; Metal-binding; Myristate; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..343
FT /note="3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic"
FT /id="PRO_0000334670"
FT DOMAIN 48..315
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT ACT_SITE 281
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 250
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 290
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 343 AA; 36650 MW; 1C9400381FB979DC CRC64;
MGNLPSAAKH CLNYQQLLRE HLWSGDSVAG ALDAAQEASQ LPGLPEYVKI VEVGPRDGLQ
NEKVIVPTDI KIELINQLSQ TGLSVIEVTS FVSSRWVPQM ADHAEVMRGI RQYPGVRYPV
LTPNLQGFQH AVAAGATEIA VFGAASESFS KKNINCSIEE SMGRFQEVIS SARHMDIPVR
GYVSCALGCP YEGSITPQKV TEVSKRLYGM GCYEISLGDT IGVGTPGSMK MMLESVMKEI
PPGALAVHCH DTYGQALANI LTALQMGINV VDSAVSGLGG CPYAKGASGN VATEDLIYML
NGMGLNTGVD LYKVMEAGEF ICKAVNKTTN SKVAQASFNA RLE
