ID GCDH_HUMAN Reviewed; 438 AA. AC Q92947; A8K2Z2; O14719; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 224. DE RecName: Full=Glutaryl-CoA dehydrogenase, mitochondrial; DE Short=GCD; DE EC=1.3.8.6; DE Flags: Precursor; GN Name=GCDH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC TISSUE=Liver; RX PubMed=1438360; RA Goodman S.I., Kratz L.E., Frerman F.E.; RT "Pork and human cDNAs encoding glutaryl-CoA dehydrogenase."; RL Prog. Clin. Biol. Res. 375:169-173(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), FUNCTION, CATALYTIC RP ACTIVITY, AND VARIANT GA1 HIS-295. RC TISSUE=Liver; RX PubMed=8541831; DOI=10.1093/hmg/4.9.1493; RA Goodman S.I., Kratz L.E., Digiulio K.A., Biery B.J., Goodman K.E., RA Isaya G., Frerman F.E.; RT "Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type RT and mutant enzymes in Escherichia coli."; RL Hum. Mol. Genet. 4:1493-1498(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GA1 CYS-88; LEU-94; RP ILE-148; GLN-161; THR-191; THR-195; PRO-227; GLN-257; TRP-257; SER-278; RP TRP-294; THR-349; SER-354; HIS-355; MET-400; TRP-402; MET-429 AND GLU-433. RX PubMed=9600243; DOI=10.1007/s004390050720; RA Schwartz M., Christensen E., Superti-Furga A., Brandt N.J.; RT "The human glutaryl-CoA dehydrogenase gene: report of intronic sequences RT and of 13 novel mutations causing glutaric aciduria type I."; RL Hum. Genet. 102:452-458(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Lymph; 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 [9] RP FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=6423663; DOI=10.1172/jci111271; RA Hyman D.B., Tanaka K.; RT "Specific glutaryl-CoA dehydrogenating activity is deficient in cultured RT fibroblasts from glutaric aciduria patients."; RL J. Clin. Invest. 73:778-784(1984). RN [10] RP VARIANTS GA1 TYR-115; VAL-122; GLY-128; GLY-138; LEU-139; ARG-178; ARG-179; RP LEU-236; VAL-266; SER-308; TRP-309; TRP-313; GLU-333; ARG-354; CYS-355; RP LYS-365; THR-382; CYS-383; HIS-383; GLN-386; ALA-390; ASP-392; GLN-402; RP ARG-403; LYS-406; PRO-407; LYS-414; THR-421 AND VAL-421, AND VARIANTS RP THR-298 AND VAL-298. RX PubMed=9711871; RX DOI=10.1002/(sici)1098-1004(1998)12:3<141::aid-humu1>3.0.co;2-k; RA Goodman S.I., Stein D.E., Schlesinger S., Christensen E., Schwartz M., RA Greenberg C.R., Elpeleg O.N.; RT "Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review RT and report of thirty novel mutations."; RL Hum. Mutat. 12:141-144(1998). RN [11] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17176108; DOI=10.1021/bi0609016; RA Rao K.S., Albro M., Dwyer T.M., Frerman F.E.; RT "Kinetic mechanism of glutaryl-CoA dehydrogenase."; RL Biochemistry 45:15853-15861(2006). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-438 IN COMPLEXES WITH SUBSTRATE RP ANALOG AND FAD, AND SUBUNIT. RX PubMed=15274622; DOI=10.1021/bi049290c; RA Fu Z., Wang M., Paschke R., Rao K.S., Frerman F.E., Kim J.-J.P.; RT "Crystal structures of human glutaryl-CoA dehydrogenase with and without an RT alternate substrate: structural bases of dehydrogenation and RT decarboxylation reactions."; RL Biochemistry 43:9674-9684(2004). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 45-438 OF MUTANT ASP-414 IN RP COMPLEXES WITH SUBSTRATE AND FAD. RX PubMed=18020372; DOI=10.1021/bi7009597; RA Rao K.S., Fu Z., Albro M., Narayanan B., Baddam S., Lee H.-J.K., RA Kim J.-J.P., Frerman F.E.; RT "The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton RT transfer to the dienolate intermediate."; RL Biochemistry 46:14468-14477(2007). RN [17] RP VARIANTS GA1. RX PubMed=8900227; RA Biery B.J., Stein D.E., Morton D.H., Goodman S.I.; RT "Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: RT impaired association of enzyme subunits that is due to an A421V RT substitution causes glutaric acidemia type I in the Amish."; RL Am. J. Hum. Genet. 59:1006-1011(1996). RN [18] RP VARIANTS GA1 ARG-101; PRO-283; THR-293; LEU-305; ARG-390 AND ILE-416. RX PubMed=8900228; RA Anikster Y., Shaag A., Joseph A., Mandel H., Ben-Zeev B., Christensen E., RA Elpeleg O.N.; RT "Glutaric aciduria type I in the Arab and Jewish communities in Israel."; RL Am. J. Hum. Genet. 59:1012-1018(1996). RN [19] RP VARIANT GA1 VAL-263. RX PubMed=14707522; DOI=10.1023/b:boli.0000005604.90621.e2; RA Muehlhausen C., Christensen E., Schwartz M., Muschol N., Ullrich K., RA Lukacs Z.; RT "Severe phenotype despite high residual glutaryl-CoA dehydrogenase RT activity: a novel mutation in a Turkish patient with glutaric aciduria type RT I."; RL J. Inherit. Metab. Dis. 26:713-714(2003). RN [20] RP CHARACTERIZATION OF VARIANTS GA1 GLY-138; TRP-402 AND LYS-414, AND SUBUNIT. RX PubMed=18775954; DOI=10.1093/hmg/ddn284; RA Keyser B., Muehlhausen C., Dickmanns A., Christensen E., Muschol N., RA Ullrich K., Braulke T.; RT "Disease-causing missense mutations affect enzymatic activity, stability RT and oligomerization of glutaryl-CoA dehydrogenase (GCDH)."; RL Hum. Mol. Genet. 17:3854-3863(2008). RN [21] RP VARIANTS GA1 ASP-64; VAL-268; ARG-375; TRP-402 AND MET-429. RX PubMed=24973495; DOI=10.1016/j.clinbiochem.2014.06.017; RA Georgiou T., Nicolaidou P., Hadjichristou A., Ioannou R., Dionysiou M., RA Siama E., Chappa G., Anastasiadou V., Drousiotou A.; RT "Molecular analysis of Cypriot patients with Glutaric aciduria type I: RT Identification of two novel mutations."; RL Clin. Biochem. 47:1300-1305(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. Isoform Short is inactive. CC {ECO:0000269|PubMed:17176108, ECO:0000269|PubMed:6423663, CC ECO:0000269|PubMed:8541831}. 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 Evidence={ECO:0000269|PubMed:8541831}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC -!- ACTIVITY REGULATION: Strongly inhibited by MCPA-CoA, a metabolite of CC hypoglycin which is present in unripened fruit of the ackee tree. CC {ECO:0000269|PubMed:6423663}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=4.7 uM for glutaryl-CoA (at pH 6.5) {ECO:0000269|PubMed:17176108, CC ECO:0000269|PubMed:6423663}; CC KM=5.5 uM for glutaryl-CoA (at pH 7.5) {ECO:0000269|PubMed:17176108, CC ECO:0000269|PubMed:6423663}; CC KM=8.1 uM for glutaryl-CoA (at pH 7.6) {ECO:0000269|PubMed:17176108, CC ECO:0000269|PubMed:6423663}; CC KM=34 uM for glutaryl-CoA (at pH 8.5) {ECO:0000269|PubMed:17176108, CC ECO:0000269|PubMed:6423663}; CC Note=Release of crotonyl-CoA product from the enzyme is the CC rate-determining step in its steady-state turnover.; CC -!- PATHWAY: Amino-acid metabolism; lysine degradation. CC -!- PATHWAY: Amino-acid metabolism; tryptophan metabolism. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15274622, CC ECO:0000269|PubMed:18775954}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q92947-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q92947-2; Sequence=VSP_000145; CC -!- TISSUE SPECIFICITY: Isoform Long and isoform Short are expressed in CC fibroblasts and liver. CC -!- DISEASE: Glutaric aciduria 1 (GA1) [MIM:231670]: An autosomal recessive CC metabolic disorder characterized by progressive dystonia and athetosis CC due to gliosis and neuronal loss in the basal ganglia. CC {ECO:0000269|PubMed:14707522, ECO:0000269|PubMed:18775954, CC ECO:0000269|PubMed:24973495, ECO:0000269|PubMed:8541831, CC ECO:0000269|PubMed:8900227, ECO:0000269|PubMed:8900228, CC ECO:0000269|PubMed:9600243, ECO:0000269|PubMed:9711871}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U69141; AAB08455.1; -; mRNA. DR EMBL; AF012342; AAC52079.1; -; Genomic_DNA. DR EMBL; AF012339; AAC52079.1; JOINED; Genomic_DNA. DR EMBL; AF012340; AAC52079.1; JOINED; Genomic_DNA. DR EMBL; AF012341; AAC52079.1; JOINED; Genomic_DNA. DR EMBL; BT006706; AAP35352.1; -; mRNA. DR EMBL; AK290407; BAF83096.1; -; mRNA. DR EMBL; AD000092; AAB51174.1; -; Genomic_DNA. DR EMBL; CH471106; EAW84324.1; -; Genomic_DNA. DR EMBL; BC002579; AAH02579.1; -; mRNA. DR CCDS; CCDS12286.1; -. [Q92947-1] DR PIR; T44260; T44260. DR PIR; T45073; T45073. DR RefSeq; NP_000150.1; NM_000159.3. [Q92947-1] DR RefSeq; NP_039663.1; NM_013976.3. [Q92947-2] DR PDB; 1SIQ; X-ray; 2.10 A; A=47-438. DR PDB; 1SIR; X-ray; 2.60 A; A=45-438. DR PDB; 2R0M; X-ray; 2.70 A; A=45-438. DR PDB; 2R0N; X-ray; 2.30 A; A=45-438. DR PDBsum; 1SIQ; -. DR PDBsum; 1SIR; -. DR PDBsum; 2R0M; -. DR PDBsum; 2R0N; -. DR AlphaFoldDB; Q92947; -. DR SMR; Q92947; -. DR BioGRID; 108909; 102. DR IntAct; Q92947; 33. DR MINT; Q92947; -. DR STRING; 9606.ENSP00000466845; -. DR BindingDB; Q92947; -. DR ChEMBL; CHEMBL3817721; -. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB03245; S-4-Nitrobutyryl-CoA. DR iPTMnet; Q92947; -. DR PhosphoSitePlus; Q92947; -. DR SwissPalm; Q92947; -. DR BioMuta; GCDH; -. DR DMDM; 2492631; -. DR EPD; Q92947; -. DR jPOST; Q92947; -. DR MassIVE; Q92947; -. DR MaxQB; Q92947; -. DR PaxDb; 9606-ENSP00000222214; -. DR PeptideAtlas; Q92947; -. DR ProteomicsDB; 75618; -. [Q92947-1] DR ProteomicsDB; 75619; -. [Q92947-2] DR Pumba; Q92947; -. DR Antibodypedia; 26250; 276 antibodies from 26 providers. DR DNASU; 2639; -. DR Ensembl; ENST00000222214.10; ENSP00000222214.4; ENSG00000105607.13. [Q92947-1] DR Ensembl; ENST00000591470.5; ENSP00000466845.1; ENSG00000105607.13. [Q92947-1] DR GeneID; 2639; -. DR KEGG; hsa:2639; -. DR MANE-Select; ENST00000222214.10; ENSP00000222214.4; NM_000159.4; NP_000150.1. DR UCSC; uc002mvq.5; human. [Q92947-1] DR AGR; HGNC:4189; -. DR DisGeNET; 2639; -. DR GeneCards; GCDH; -. DR GeneReviews; GCDH; -. DR HGNC; HGNC:4189; GCDH. DR HPA; ENSG00000105607; Tissue enhanced (liver). DR MalaCards; GCDH; -. DR MIM; 231670; phenotype. DR MIM; 608801; gene. DR neXtProt; NX_Q92947; -. DR OpenTargets; ENSG00000105607; -. DR Orphanet; 25; Glutaryl-CoA dehydrogenase deficiency. DR PharmGKB; PA28604; -. DR VEuPathDB; HostDB:ENSG00000105607; -. DR eggNOG; KOG0138; Eukaryota. DR GeneTree; ENSGT00940000158116; -. DR HOGENOM; CLU_018204_8_0_1; -. DR InParanoid; Q92947; -. DR OMA; HMMNLES; -. DR OrthoDB; 275353at2759; -. DR PhylomeDB; Q92947; -. DR TreeFam; TF105051; -. DR BRENDA; 1.3.8.6; 2681. DR PathwayCommons; Q92947; -. DR Reactome; R-HSA-71064; Lysine catabolism. DR SABIO-RK; Q92947; -. DR SignaLink; Q92947; -. DR UniPathway; UPA00224; -. DR UniPathway; UPA00225; -. DR BioGRID-ORCS; 2639; 19 hits in 1166 CRISPR screens. DR ChiTaRS; GCDH; human. DR EvolutionaryTrace; Q92947; -. DR GenomeRNAi; 2639; -. DR Pharos; Q92947; Tbio. DR PRO; PR:Q92947; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q92947; Protein. DR Bgee; ENSG00000105607; Expressed in right lobe of liver and 181 other cell types or tissues. DR ExpressionAtlas; Q92947; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0000062; F:fatty-acyl-CoA binding; IBA:GO_Central. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central. DR GO; GO:0004361; F:glutaryl-CoA dehydrogenase activity; IDA:HGNC. DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:UniProtKB. DR GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; IBA:GO_Central. 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; PS00072; ACYL_COA_DH_1; 1. DR PROSITE; PS00073; ACYL_COA_DH_2; 1. DR Genevisible; Q92947; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; FAD; KW Flavoprotein; Glutaricaciduria; 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_0000000526" FT ACT_SITE 414 FT /note="Proton acceptor" FT /evidence="ECO:0000305" FT BINDING 138..139 FT /ligand="substrate" FT BINDING 177..186 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT BINDING 186 FT /ligand="substrate" FT BINDING 212..214 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT BINDING 287..294 FT /ligand="substrate" 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 BINDING 416..418 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT BINDING 434 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT MOD_RES 240 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q60759" FT VAR_SEQ 415..438 FT /note="GTHDIHALILGRAITGIQAFTASK -> VVQMCSLKRRWNSL (in FT isoform Short)" FT /evidence="ECO:0000303|PubMed:8541831" FT /id="VSP_000145" FT VARIANT 64 FT /note="E -> D (in GA1; dbSNP:rs1555749239)" FT /evidence="ECO:0000269|PubMed:24973495" FT /id="VAR_071510" FT VARIANT 88 FT /note="R -> C (in GA1; dbSNP:rs142967670)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000366" FT VARIANT 94 FT /note="R -> L (in GA1; dbSNP:rs566417795)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000367" FT VARIANT 101 FT /note="G -> R (in GA1; dbSNP:rs1273164833)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000368" FT VARIANT 115 FT /note="C -> Y (in GA1; dbSNP:rs776758971)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000369" FT VARIANT 122 FT /note="A -> V (in GA1; dbSNP:rs766325846)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000370" FT VARIANT 128 FT /note="R -> G (in GA1)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000371" FT VARIANT 138 FT /note="R -> G (in GA1; impaired protein stability; loss of FT activity; dbSNP:rs897036690)" FT /evidence="ECO:0000269|PubMed:18775954, FT ECO:0000269|PubMed:9711871" FT /id="VAR_000372" FT VARIANT 139 FT /note="S -> L (in GA1; dbSNP:rs139851890)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000373" FT VARIANT 148 FT /note="V -> I (in GA1; dbSNP:rs1003611285)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000374" FT VARIANT 161 FT /note="R -> Q (in GA1; dbSNP:rs777201305)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000375" FT VARIANT 178 FT /note="G -> R (in GA1; dbSNP:rs749452002)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000376" FT VARIANT 179 FT /note="L -> R (in GA1; dbSNP:rs774526353)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000377" FT VARIANT 191 FT /note="M -> T (in GA1; dbSNP:rs149120354)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000378" FT VARIANT 195 FT /note="A -> T (in GA1)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000379" FT VARIANT 227 FT /note="R -> P (in GA1; dbSNP:rs121434373)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000380" FT VARIANT 236 FT /note="F -> L (in GA1; dbSNP:rs747920711)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000381" FT VARIANT 257 FT /note="R -> Q (in GA1; dbSNP:rs751583656)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000382" FT VARIANT 257 FT /note="R -> W (in GA1; dbSNP:rs766518430)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000383" FT VARIANT 263 FT /note="M -> V (in GA1; severe phenotype; residual activity FT of 30% as measured in patient fibroblasts)" FT /evidence="ECO:0000269|PubMed:14707522" FT /id="VAR_060588" FT VARIANT 266 FT /note="M -> V (in GA1; dbSNP:rs745357523)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000384" FT VARIANT 268 FT /note="G -> V (in GA1; dbSNP:rs765723076)" FT /evidence="ECO:0000269|PubMed:24973495" FT /id="VAR_071511" FT VARIANT 278 FT /note="P -> S (in GA1; dbSNP:rs751742575)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000385" FT VARIANT 283 FT /note="L -> P (in GA1)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000386" FT VARIANT 293 FT /note="A -> T (in GA1; dbSNP:rs121434371)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000387" FT VARIANT 294 FT /note="R -> W (in GA1)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000388" FT VARIANT 295 FT /note="Y -> H (in GA1; dbSNP:rs121434366)" FT /evidence="ECO:0000269|PubMed:8541831" FT /id="VAR_000389" FT VARIANT 298 FT /note="A -> T (in dbSNP:rs761765983)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000390" FT VARIANT 298 FT /note="A -> V (in dbSNP:rs764993096)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000391" FT VARIANT 305 FT /note="S -> L (in GA1; dbSNP:rs1260580183)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000392" FT VARIANT 308 FT /note="C -> S (in GA1; dbSNP:rs1205368991)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000393" FT VARIANT 309 FT /note="L -> W (in GA1; dbSNP:rs1247712895)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000394" FT VARIANT 313 FT /note="R -> W (in GA1; dbSNP:rs779315456)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000395" FT VARIANT 333 FT /note="Q -> E (in GA1; dbSNP:rs794726972)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000396" FT VARIANT 349 FT /note="A -> T (in GA1; dbSNP:rs1257292639)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000397" FT VARIANT 354 FT /note="G -> R (in GA1)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000398" FT VARIANT 354 FT /note="G -> S (in GA1; dbSNP:rs768925619)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000399" FT VARIANT 355 FT /note="R -> C (in GA1; dbSNP:rs781477694)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000400" FT VARIANT 355 FT /note="R -> H (in GA1; dbSNP:rs748275416)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000401" FT VARIANT 365 FT /note="E -> K (in GA1; dbSNP:rs121434370)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000402" FT VARIANT 375 FT /note="C -> R (in GA1; dbSNP:rs1348974766)" FT /evidence="ECO:0000269|PubMed:24973495" FT /id="VAR_000403" FT VARIANT 382 FT /note="A -> T (in GA1; dbSNP:rs567564095)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000404" FT VARIANT 383 FT /note="R -> C (in GA1; dbSNP:rs150938052)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000405" FT VARIANT 383 FT /note="R -> H (in GA1; dbSNP:rs764608975)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000406" FT VARIANT 386 FT /note="R -> Q (in GA1; dbSNP:rs398123190)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000407" FT VARIANT 390 FT /note="G -> A (in GA1; dbSNP:rs778153326)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000409" FT VARIANT 390 FT /note="G -> R (in GA1; dbSNP:rs372983141)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000408" FT VARIANT 392 FT /note="N -> D (in GA1; dbSNP:rs1282266790)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000410" FT VARIANT 400 FT /note="V -> M (in GA1; dbSNP:rs121434372)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000411" FT VARIANT 402 FT /note="R -> Q (in GA1; dbSNP:rs786204626)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000413" FT VARIANT 402 FT /note="R -> W (in GA1; most common mutation identified; FT loss of tetramerization; loss enzyme activity; FT dbSNP:rs121434369)" FT /evidence="ECO:0000269|PubMed:18775954, FT ECO:0000269|PubMed:24973495, ECO:0000269|PubMed:9600243" FT /id="VAR_000412" FT VARIANT 403 FT /note="H -> R (in GA1)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000414" FT VARIANT 406 FT /note="N -> K (in GA1)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000415" FT VARIANT 407 FT /note="L -> P (in GA1; dbSNP:rs1555751379)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000416" FT VARIANT 414 FT /note="E -> K (in GA1; loss of enzyme activity; FT dbSNP:rs147611168)" FT /evidence="ECO:0000269|PubMed:18775954, FT ECO:0000269|PubMed:9711871" FT /id="VAR_000417" FT VARIANT 416 FT /note="T -> I (in GA1; dbSNP:rs121434368)" FT /evidence="ECO:0000269|PubMed:8900228" FT /id="VAR_000418" FT VARIANT 421 FT /note="A -> T (in GA1; dbSNP:rs151201155)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000419" FT VARIANT 421 FT /note="A -> V (in GA1; impaired association of subunits; FT dbSNP:rs121434367)" FT /evidence="ECO:0000269|PubMed:9711871" FT /id="VAR_000420" FT VARIANT 429 FT /note="T -> M (in GA1; dbSNP:rs745360675)" FT /evidence="ECO:0000269|PubMed:24973495, FT ECO:0000269|PubMed:9600243" FT /id="VAR_000421" FT VARIANT 433 FT /note="A -> E (in GA1; dbSNP:rs933624223)" FT /evidence="ECO:0000269|PubMed:9600243" FT /id="VAR_000422" FT MUTAGEN 414 FT /note="E->D: Reduced catalytic activity." FT CONFLICT 33 FT /note="G -> A (in Ref. 1; AAC52079)" FT /evidence="ECO:0000305" FT HELIX 56..59 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 62..78 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 80..89 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 95..102 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 120..131 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 135..146 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 149..155 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 158..169 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 184..186 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 194..198 FT /evidence="ECO:0007829|PDB:1SIQ" FT TURN 199..202 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 203..214 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 220..228 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 233..239 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 261..272 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 284..318 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 330..358 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 364..388 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 389..394 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 396..398 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 400..410 FT /evidence="ECO:0007829|PDB:1SIQ" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:1SIQ" FT HELIX 417..429 FT /evidence="ECO:0007829|PDB:1SIQ" SQ SEQUENCE 438 AA; 48127 MW; 415B8D510027BB63 CRC64; MALRGVSVRL LSRGPGLHVL RTWVSSAAQT EKGGRTQSQL AKSSRPEFDW QDPLVLEEQL TTDEILIRDT FRTYCQERLM PRILLANRNE VFHREIISEM GELGVLGPTI KGYGCAGVSS VAYGLLAREL ERVDSGYRSA MSVQSSLVMH PIYAYGSEEQ RQKYLPQLAK GELLGCFGLT EPNSGSDPSS METRAHYNSS NKSYTLNGTK TWITNSPMAD LFVVWARCED GCIRGFLLEK GMRGLSAPRI QGKFSLRASA TGMIIMDGVE VPEENVLPGA SSLGGPFGCL NNARYGIAWG VLGASEFCLH TARQYALDRM QFGVPLARNQ LIQKKLADML TEITLGLHAC LQLGRLKDQD KAAPEMVSLL KRNNCGKALD IARQARDMLG GNGISDEYHV IRHAMNLEAV NTYEGTHDIH ALILGRAITG IQAFTASK //