HMGC2_RAT
ID HMGC2_RAT Reviewed; 343 AA.
AC D4A5C3;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 75.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=22865860; DOI=10.1074/jbc.m112.393231;
RA Montgomery C., Pei Z., Watkins P.A., Miziorko H.M.;
RT "Identification and characterization of an extramitochondrial human 3-
RT Hydroxy-3-methylglutaryl-CoA lyase.";
RL J. Biol. Chem. 287:33227-33236(2012).
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 -!- TISSUE SPECIFICITY: Present at high level in duodenum and small
CC intestine (at protein level). {ECO:0000269|PubMed:22865860}.
CC -!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
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DR EMBL; CH473954; EDL77774.1; -; Genomic_DNA.
DR RefSeq; NP_001263401.1; NM_001276472.1.
DR AlphaFoldDB; D4A5C3; -.
DR SMR; D4A5C3; -.
DR STRING; 10116.ENSRNOP00000014927; -.
DR iPTMnet; D4A5C3; -.
DR PhosphoSitePlus; D4A5C3; -.
DR PaxDb; D4A5C3; -.
DR PeptideAtlas; D4A5C3; -.
DR PRIDE; D4A5C3; -.
DR Ensembl; ENSRNOT00000014926; ENSRNOP00000014927; ENSRNOG00000011193.
DR GeneID; 367112; -.
DR KEGG; rno:367112; -.
DR UCSC; RGD:1565090; rat.
DR CTD; 54511; -.
DR RGD; 1565090; Hmgcll1.
DR eggNOG; KOG2368; Eukaryota.
DR GeneTree; ENSGT00940000159467; -.
DR HOGENOM; CLU_022138_3_1_1; -.
DR InParanoid; D4A5C3; -.
DR OMA; FHNTRGT; -.
DR OrthoDB; 1029775at2759; -.
DR PhylomeDB; D4A5C3; -.
DR TreeFam; TF105363; -.
DR Reactome; R-RNO-77111; Synthesis of Ketone Bodies.
DR UniPathway; UPA00896; UER00863.
DR PRO; PR:D4A5C3; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR Bgee; ENSRNOG00000011193; Expressed in cerebellum and 10 other tissues.
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; IEA:UniProtKB-KW.
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 1: Evidence at protein 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_0000419685"
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; 36549 MW; 1EA209972A3AD2BF CRC64;
MGNLPSAAKH CLNYQQLLRE HLWSGESVAG ALDPAQEASQ LSGLPEYVKI VEVGPRDGLQ
NEKVIVPTDI KIEFINQLSQ TGLSVIEVTS FVSSRWVPQM ADHAEVMGGI HQYPGVRYPV
LVPNLQGLQH AVAAGATEIA VFGAASESFS KKNINCSIEE SMGRFEQVIS SARHMNIPVR
GYVSCALGCP YEGSIMPQKV TEVSKRLYSM GCYEISLGDT VGVGTPGSMK TMLESVMKEI
PPGALAVHCH DTYGQALANI LTALQMGINV VDSAVSGLGG CPYAKGASGN VATEDLIYML
NGMGLNTGVD LHKVMEAGDF ICKAVNKTTN SKVAQASFKA RLE
