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   27-MAR-2024, entry version 171.
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,
RC   Pancreas, 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; 10090-ENSMUSP00000003907; -.
DR   PeptideAtlas; Q60759; -.
DR   ProteomicsDB; 268855; -.
DR   Pumba; Q60759; -.
DR   Antibodypedia; 26250; 276 antibodies from 26 providers.
DR   DNASU; 270076; -.
DR   Ensembl; ENSMUST00000109745.8; ENSMUSP00000105367.2; ENSMUSG00000003809.15.
DR   GeneID; 270076; -.
DR   KEGG; mmu:270076; -.
DR   AGR; MGI:104541; -.
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; HMMNLES; -.
DR   OrthoDB; 275353at2759; -.
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 79 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 265 other cell types or tissues.
DR   ExpressionAtlas; Q60759; baseline and differential.
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   CDD; cd01151; GCD; 1.
DR   Gene3D; 1.10.540.10; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1.
DR   Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1.
DR   Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 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_sf.
DR   PANTHER; PTHR42807; GLUTARYL-COA DEHYDROGENASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR42807:SF1; GLUTARYL-COA DEHYDROGENASE, MITOCHONDRIAL; 1.
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; Acyl-CoA dehydrogenase C-terminal domain-like; 1.
DR   SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1.
DR   PROSITE; PS00073; ACYL_COA_DH_2; 1.
DR   Genevisible; Q60759; MM.
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
//