GCDH_MOUSE
ID GCDH_MOUSE Reviewed; 438 AA.
AC Q60759; Q6P8N6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Glutaryl-CoA dehydrogenase, mitochondrial;
DE Short=GCD;
DE EC=1.3.8.6;
DE Flags: Precursor;
GN Name=Gcdh;
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 [MRNA].
RC STRAIN=129/Sv; TISSUE=Liver;
RX PubMed=7490088; DOI=10.1006/geno.1995.1182;
RA Koeller D.M., Digiulio K.A., Angeloni S.V., Dowler L.L., Frerman F.E.,
RA White R.A., Goodman S.I.;
RT "Cloning, structure, and chromosome localization of the mouse glutaryl-CoA
RT dehydrogenase gene.";
RL Genomics 28:508-512(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and 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).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-51, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-51; LYS-65 AND LYS-240, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=24703693; DOI=10.1016/j.cmet.2014.03.014;
RA Tan M., Peng C., Anderson K.A., Chhoy P., Xie Z., Dai L., Park J., Chen Y.,
RA Huang H., Zhang Y., Ro J., Wagner G.R., Green M.F., Madsen A.S.,
RA Schmiesing J., Peterson B.S., Xu G., Ilkayeva O.R., Muehlbauer M.J.,
RA Braulke T., Muehlhausen C., Backos D.S., Olsen C.A., McGuire P.J.,
RA Pletcher S.D., Lombard D.B., Hirschey M.D., Zhao Y.;
RT "Lysine glutarylation is a protein posttranslational modification regulated
RT by SIRT5.";
RL Cell Metab. 19:605-617(2014).
CC -!- FUNCTION: Catalyzes the oxidative decarboxylation of glutaryl-CoA to
CC crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-
CC hydroxylysine, and L-tryptophan metabolism. It uses electron transfer
CC flavoprotein as its electron acceptor.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutaryl-CoA + 2 H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-butenoyl-CoA + CO2 + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:13389, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57332,
CC ChEBI:CHEBI:57378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; EC=1.3.8.6;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC -!- PATHWAY: Amino-acid metabolism; lysine degradation.
CC -!- PATHWAY: Amino-acid metabolism; tryptophan metabolism.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- DISRUPTION PHENOTYPE: Animals show highly increased protein
CC glutarylation in liver. {ECO:0000269|PubMed:24703693}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; U18992; AAB04679.1; -; mRNA.
DR EMBL; AK165406; BAE38166.1; -; mRNA.
DR EMBL; BC061158; AAH61158.1; -; mRNA.
DR RefSeq; NP_032123.3; NM_008097.2.
DR AlphaFoldDB; Q60759; -.
DR SMR; Q60759; -.
DR BioGRID; 234755; 7.
DR IntAct; Q60759; 1.
DR STRING; 10090.ENSMUSP00000003907; -.
DR iPTMnet; Q60759; -.
DR PhosphoSitePlus; Q60759; -.
DR SwissPalm; Q60759; -.
DR EPD; Q60759; -.
DR jPOST; Q60759; -.
DR MaxQB; Q60759; -.
DR PaxDb; Q60759; -.
DR PeptideAtlas; Q60759; -.
DR PRIDE; Q60759; -.
DR ProteomicsDB; 268855; -.
DR Antibodypedia; 26250; 256 antibodies from 25 providers.
DR DNASU; 270076; -.
DR Ensembl; ENSMUST00000109745; ENSMUSP00000105367; ENSMUSG00000003809.
DR GeneID; 270076; -.
DR KEGG; mmu:270076; -.
DR CTD; 2639; -.
DR MGI; MGI:104541; Gcdh.
DR VEuPathDB; HostDB:ENSMUSG00000003809; -.
DR eggNOG; KOG0138; Eukaryota.
DR GeneTree; ENSGT00940000158116; -.
DR HOGENOM; CLU_018204_8_0_1; -.
DR InParanoid; Q60759; -.
DR OMA; AAMDCYD; -.
DR OrthoDB; 589058at2759; -.
DR TreeFam; TF105051; -.
DR BRENDA; 1.3.8.6; 3474.
DR Reactome; R-MMU-71064; Lysine catabolism.
DR UniPathway; UPA00224; -.
DR UniPathway; UPA00225; -.
DR BioGRID-ORCS; 270076; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Gcdh; mouse.
DR PRO; PR:Q60759; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q60759; protein.
DR Bgee; ENSMUSG00000003809; Expressed in right kidney and 261 other tissues.
DR ExpressionAtlas; Q60759; baseline and differential.
DR Genevisible; Q60759; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0004361; F:glutaryl-CoA dehydrogenase activity; ISO:MGI.
DR GO; GO:0006637; P:acyl-CoA metabolic process; ISO:MGI.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; ISO:MGI.
DR GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; ISO:MGI.
DR GO; GO:0006568; P:tryptophan metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006089; Acyl-CoA_DH_CS.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; FAD; Flavoprotein; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..44
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 45..438
FT /note="Glutaryl-CoA dehydrogenase, mitochondrial"
FT /id="PRO_0000000528"
FT ACT_SITE 414
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 138..139
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 177..186
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 212..214
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 287..294
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 387..391
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 416..418
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 416
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 434
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 51
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 51
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 65
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 240
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 9
FT /note="R -> Q (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="C -> W (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="R -> Q (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="G -> R (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="R -> P (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="L -> S (in Ref. 1; AAB04679)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 438 AA; 48606 MW; A904457D76F2BD90 CRC64;
MSLRGVSARL LSRRSGLRFP RFPRTWSSAA AHTEKTQIRP AKSSRPVFDW KDPLILEEQL
TADEKLIRDT FRNYCQERLM SRILLANRNE VFHRDIVYEM GELGVLGPTI KGYGCAGVSS
VAYGLLTREL ERVDSGYRSM MSVQSSLVMH PIYTYGSEEQ RQKYLPGLAK GELLGCFGLT
EPNHGSDPGG METRARHNPS NQSYTLSGTK TWITNSPVAD LFIVWARCED NCIRGFILEK
GMRGLSAPRI EGKFSLRASA TGMIIMDSVE VPEENVLPNV SSLAGPFGCL NTARYGITWG
VLGAAEFCLH TARQYALDRI QFGVPLARNQ LVQKKLADML TEITLGLHAC LQLGRLKDQD
KATPEMVSML KRNNCGKALD IARQARDILG GNGISDEYHV IRHAMNLEAV NTYEGTHDIH
ALILGRAITG IQAFTVGK
