GCDH_HUMAN
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 03-AUG-2022, entry version 215.
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.
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 REVIEW ON VARIANTS.
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=34.0 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 rate-
CC 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}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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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; 93.
DR IntAct; Q92947; 31.
DR MINT; Q92947; -.
DR STRING; 9606.ENSP00000222214; -.
DR ChEMBL; CHEMBL3817721; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB03245; S-4-Nitrobutyryl-CoA.
DR iPTMnet; Q92947; -.
DR PhosphoSitePlus; Q92947; -.
DR BioMuta; GCDH; -.
DR DMDM; 2492631; -.
DR EPD; Q92947; -.
DR jPOST; Q92947; -.
DR MassIVE; Q92947; -.
DR MaxQB; Q92947; -.
DR PaxDb; Q92947; -.
DR PeptideAtlas; Q92947; -.
DR PRIDE; Q92947; -.
DR ProteomicsDB; 75618; -. [Q92947-1]
DR ProteomicsDB; 75619; -. [Q92947-2]
DR Antibodypedia; 26250; 256 antibodies from 25 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 CTD; 2639; -.
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; AAMDCYD; -.
DR OrthoDB; 589058at2759; -.
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 1085 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 179 other tissues.
DR ExpressionAtlas; Q92947; baseline and differential.
DR Genevisible; Q92947; HS.
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 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; PS00072; ACYL_COA_DH_1; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
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 /id="VAR_000366"
FT VARIANT 94
FT /note="R -> L (in GA1; dbSNP:rs566417795)"
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 /id="VAR_000369"
FT VARIANT 122
FT /note="A -> V (in GA1; dbSNP:rs766325846)"
FT /id="VAR_000370"
FT VARIANT 128
FT /note="R -> G (in GA1)"
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 /id="VAR_000372"
FT VARIANT 139
FT /note="S -> L (in GA1; dbSNP:rs139851890)"
FT /id="VAR_000373"
FT VARIANT 148
FT /note="V -> I (in GA1; dbSNP:rs1003611285)"
FT /id="VAR_000374"
FT VARIANT 161
FT /note="R -> Q (in GA1; dbSNP:rs777201305)"
FT /id="VAR_000375"
FT VARIANT 178
FT /note="G -> R (in GA1; dbSNP:rs749452002)"
FT /id="VAR_000376"
FT VARIANT 179
FT /note="L -> R (in GA1; dbSNP:rs774526353)"
FT /id="VAR_000377"
FT VARIANT 191
FT /note="M -> T (in GA1; dbSNP:rs149120354)"
FT /id="VAR_000378"
FT VARIANT 195
FT /note="A -> T (in GA1)"
FT /id="VAR_000379"
FT VARIANT 227
FT /note="R -> P (in GA1; dbSNP:rs121434373)"
FT /id="VAR_000380"
FT VARIANT 236
FT /note="F -> L (in GA1; dbSNP:rs747920711)"
FT /id="VAR_000381"
FT VARIANT 257
FT /note="R -> Q (in GA1; dbSNP:rs751583656)"
FT /id="VAR_000382"
FT VARIANT 257
FT /note="R -> W (in GA1; dbSNP:rs766518430)"
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 /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 /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 /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 /id="VAR_000390"
FT VARIANT 298
FT /note="A -> V (in dbSNP:rs764993096)"
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 /id="VAR_000393"
FT VARIANT 309
FT /note="L -> W (in GA1; dbSNP:rs1247712895)"
FT /id="VAR_000394"
FT VARIANT 313
FT /note="R -> W (in GA1; dbSNP:rs779315456)"
FT /id="VAR_000395"
FT VARIANT 333
FT /note="Q -> E (in GA1; dbSNP:rs794726972)"
FT /id="VAR_000396"
FT VARIANT 349
FT /note="A -> T (in GA1; dbSNP:rs1257292639)"
FT /id="VAR_000397"
FT VARIANT 354
FT /note="G -> R (in GA1)"
FT /id="VAR_000398"
FT VARIANT 354
FT /note="G -> S (in GA1; dbSNP:rs768925619)"
FT /id="VAR_000399"
FT VARIANT 355
FT /note="R -> C (in GA1; dbSNP:rs781477694)"
FT /id="VAR_000400"
FT VARIANT 355
FT /note="R -> H (in GA1; dbSNP:rs748275416)"
FT /id="VAR_000401"
FT VARIANT 365
FT /note="E -> K (in GA1; dbSNP:rs121434370)"
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 /id="VAR_000404"
FT VARIANT 383
FT /note="R -> C (in GA1; dbSNP:rs150938052)"
FT /id="VAR_000405"
FT VARIANT 383
FT /note="R -> H (in GA1; dbSNP:rs764608975)"
FT /id="VAR_000406"
FT VARIANT 386
FT /note="R -> Q (in GA1; dbSNP:rs398123190)"
FT /id="VAR_000407"
FT VARIANT 390
FT /note="G -> A (in GA1; dbSNP:rs778153326)"
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 /id="VAR_000410"
FT VARIANT 400
FT /note="V -> M (in GA1; dbSNP:rs121434372)"
FT /id="VAR_000411"
FT VARIANT 402
FT /note="R -> Q (in GA1; dbSNP:rs786204626)"
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"
FT /id="VAR_000412"
FT VARIANT 403
FT /note="H -> R (in GA1)"
FT /id="VAR_000414"
FT VARIANT 406
FT /note="N -> K (in GA1)"
FT /id="VAR_000415"
FT VARIANT 407
FT /note="L -> P (in GA1; dbSNP:rs1555751379)"
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 /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 /id="VAR_000419"
FT VARIANT 421
FT /note="A -> V (in GA1; impaired association of subunits;
FT dbSNP:rs121434367)"
FT /id="VAR_000420"
FT VARIANT 429
FT /note="T -> M (in GA1; dbSNP:rs745360675)"
FT /evidence="ECO:0000269|PubMed:24973495"
FT /id="VAR_000421"
FT VARIANT 433
FT /note="A -> E (in GA1; dbSNP:rs933624223)"
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
