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Reviewed, UniProtKB/Swiss-Prot Q92947 (GCDH_HUMAN)

Last modified June 16, 2009. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Glutaryl-CoA dehydrogenase, mitochondrial
      Short name=GCD
    EC=1.3.99.7
Gene names
Name: GCDH
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length438 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO2 in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The short isoform is inactive.

Catalytic activity

Glutaryl-CoA + acceptor = crotonoyl-CoA + CO2 + reduced acceptor.

Cofactor

FAD.

Pathway

Amino-acid metabolism; lysine degradation.

Amino-acid metabolism; tryptophan metabolism.

Subunit structure

Homotetramer. Ref.9 Ref.13

Subcellular location

Mitochondrion matrix.

Tissue specificity

The 2 isoforms have been found in fibroblasts and liver.

Involvement in disease

Defects in GCDH are the cause of glutaric aciduria type 1 (GA1) [MIM:231670]. GA1 is an autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia. Ref.13 Ref.2 Ref.3 Ref.11 Ref.12

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Glutaricaciduria
   DomainTransit peptide
   LigandFAD
Flavoprotein
   Molecular functionOxidoreductase
   Technical term3D-structure
Gene Ontology (GO)
   Biological processoxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentmitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionFAD binding

Inferred from electronic annotation. Source: InterPro

electron carrier activity

Inferred from electronic annotation. Source: InterPro

glutaryl-CoA dehydrogenase activity Ref.2

Traceable author statement. Source: ProtInc

protein binding

Inferred from physical interaction. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GRB2P629931EBI-1236978,EBI-401755

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q92947-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: Q92947-2)

The sequence of this isoform differs from the canonical sequence as follows:
     415-438: GTHDIHALILGRAITGIQAFTASK → VVQMCSLKRRWNSL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4444Mitochondrion Potential
Chain45 – 438394Glutaryl-CoA dehydrogenase, mitochondrial
PRO_0000000526

Regions

Nucleotide binding177 – 1804FAD
Nucleotide binding212 – 2143FAD
Region138 – 1392Substrate binding
Region287 – 2915Substrate binding

Sites

Active site4141Proton acceptor Probable
Binding site1861FAD
Binding site1861Substrate; via carbonyl oxygen
Binding site2941Substrate
Binding site4161FAD
Binding site4341FAD; via carbonyl oxygen

Natural variations

Alternative sequence415 – 43824GTHDI…FTASK → VVQMCSLKRRWNSL in isoform Short.
VSP_000145
Natural variant881R → C in GA1.
VAR_000366
Natural variant941R → L in GA1.
VAR_000367
Natural variant1011G → R in GA1. Ref.12
VAR_000368
Natural variant1151C → Y in GA1.
VAR_000369
Natural variant1221A → V in GA1.
VAR_000370
Natural variant1281R → G in GA1.
VAR_000371
Natural variant1381R → G in GA1; impaired protein stability and loss of activity. Ref.13
VAR_000372
Natural variant1391S → L in GA1.
VAR_000373
Natural variant1481V → I in GA1.
VAR_000374
Natural variant1611R → Q in GA1.
VAR_000375
Natural variant1781G → R in GA1.
VAR_000376
Natural variant1791L → R in GA1.
VAR_000377
Natural variant1911M → T in GA1.
VAR_000378
Natural variant1951A → T in GA1.
VAR_000379
Natural variant2271R → P in GA1.
VAR_000380
Natural variant2361F → L in GA1.
VAR_000381
Natural variant2571R → Q in GA1.
VAR_000382
Natural variant2571R → W in GA1.
VAR_000383
Natural variant2661M → V in GA1.
VAR_000384
Natural variant2781P → S in GA1.
VAR_000385
Natural variant2831L → P in GA1. Ref.12
VAR_000386
Natural variant2931A → T in GA1. Ref.12
VAR_000387
Natural variant2941R → W in GA1.
VAR_000388
Natural variant2951Y → H in GA1. Ref.2
VAR_000389
Natural variant2981A → T
VAR_000390
Natural variant2981A → V
VAR_000391
Natural variant3051S → L in GA1. Ref.12
VAR_000392
Natural variant3081C → S in GA1.
VAR_000393
Natural variant3091L → W in GA1.
VAR_000394
Natural variant3131R → W in GA1.
VAR_000395
Natural variant3331Q → E in GA1.
VAR_000396
Natural variant3491A → T in GA1.
VAR_000397
Natural variant3541G → R in GA1.
VAR_000398
Natural variant3541G → S in GA1.
VAR_000399
Natural variant3551R → C in GA1.
VAR_000400
Natural variant3551R → H in GA1.
VAR_000401
Natural variant3651E → K in GA1.
VAR_000402
Natural variant3751C → R in GA1.
VAR_000403
Natural variant3821A → T in GA1.
VAR_000404
Natural variant3831R → C in GA1.
VAR_000405
Natural variant3831R → H in GA1.
VAR_000406
Natural variant3861R → Q in GA1.
VAR_000407
Natural variant3901G → A in GA1. Ref.12
VAR_000409
Natural variant3901G → R in GA1. Ref.12
VAR_000408
Natural variant3921N → D in GA1.
VAR_000410
Natural variant4001V → M in GA1.
VAR_000411
Natural variant4021R → Q in GA1. Ref.13
VAR_000413
Natural variant4021R → W in GA1; most common mutation identified; loss of tetramerization and enzyme activity. Ref.13
VAR_000412
Natural variant4031H → R in GA1.
VAR_000414
Natural variant4061N → K in GA1.
VAR_000415
Natural variant4071L → P in GA1.
VAR_000416
Natural variant4141E → K in GA1; loss of enzyme activity. Ref.13
VAR_000417
Natural variant4161T → I in GA1. Ref.12
VAR_000418
Natural variant4211A → T in GA1.
VAR_000419
Natural variant4211A → V in GA1; impaired association of subunits.
VAR_000420
Natural variant4291T → M in GA1.
VAR_000421
Natural variant4331A → E in GA1.
VAR_000422

Experimental info

Mutagenesis4141E → D: Reduced catalytic activity.
Sequence conflict331G → A in AAC52079. Ref.1

Secondary structure

....................................................... 438
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 415B8D510027BB63

FASTA43848,127
        10         20         30         40         50         60 
MALRGVSVRL LSRGPGLHVL RTWVSSAAQT EKGGRTQSQL AKSSRPEFDW QDPLVLEEQL 

        70         80         90        100        110        120 
TTDEILIRDT FRTYCQERLM PRILLANRNE VFHREIISEM GELGVLGPTI KGYGCAGVSS 

       130        140        150        160        170        180 
VAYGLLAREL ERVDSGYRSA MSVQSSLVMH PIYAYGSEEQ RQKYLPQLAK GELLGCFGLT 

       190        200        210        220        230        240 
EPNSGSDPSS METRAHYNSS NKSYTLNGTK TWITNSPMAD LFVVWARCED GCIRGFLLEK 

       250        260        270        280        290        300 
GMRGLSAPRI QGKFSLRASA TGMIIMDGVE VPEENVLPGA SSLGGPFGCL NNARYGIAWG 

       310        320        330        340        350        360 
VLGASEFCLH TARQYALDRM QFGVPLARNQ LIQKKLADML TEITLGLHAC LQLGRLKDQD 

       370        380        390        400        410        420 
KAAPEMVSLL KRNNCGKALD IARQARDMLG GNGISDEYHV IRHAMNLEAV NTYEGTHDIH 

       430 
ALILGRAITG IQAFTASK 

« Hide

Isoform Short.

Checksum: 8E9E298E6DA9433C
Show »

FASTA42847,355

References

« Hide 'large scale' references
[1]"Pork and human cDNAs encoding glutaryl-CoA dehydrogenase."
Goodman S.I., Kratz L.E., Frerman F.E.
Prog. Clin. Biol. Res. 375:169-173(1992) [PubMed: 1438360] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Liver.
[2]"Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli."
Goodman S.I., Kratz L.E., Digiulio K.A., Biery B.J., Goodman K.E., Isaya G., Frerman F.E.
Hum. Mol. Genet. 4:1493-1498(1995) [PubMed: 8541831] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), VARIANT GA1 HIS-295.
Tissue: Liver.
[3]"The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I."
Schwartz M., Christensen E., Superti-Furga A., Brandt N.J.
Hum. Genet. 102:452-458(1998) [PubMed: 9600243] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GA1.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed: 15057824] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Lymph.
[7]"Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations."
Goodman S.I., Stein D.E., Schlesinger S., Christensen E., Schwartz M., Greenberg C.R., Elpeleg O.N.
Hum. Mutat. 12:141-144(1998) [PubMed: 9711871] [Abstract]
Cited for: REVIEW ON VARIANTS.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]"Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions."
Fu Z., Wang M., Paschke R., Rao K.S., Frerman F.E., Kim J.-J.P.
Biochemistry 43:9674-9684(2004) [PubMed: 15274622] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-438 IN COMPLEXES WITH SUBSTRATE ANALOG AND FAD, SUBUNIT.
[10]"The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate."
Rao K.S., Fu Z., Albro M., Narayanan B., Baddam S., Lee H.-J.K., Kim J.-J.P., Frerman F.E.
Biochemistry 46:14468-14477(2007) [PubMed: 18020372] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 45-438 OF MUTANT ASP-414 IN COMPLEXES WITH SUBSTRATE AND FAD.
[11]"Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish."
Biery B.J., Stein D.E., Morton D.H., Goodman S.I.
Am. J. Hum. Genet. 59:1006-1011(1996) [PubMed: 8900227] [Abstract]
Cited for: VARIANTS GA1.
[12]"Glutaric aciduria type I in the Arab and Jewish communities in Israel."
Anikster Y., Shaag A., Joseph A., Mandel H., Ben-Zeev B., Christensen E., Elpeleg O.N.
Am. J. Hum. Genet. 59:1012-1018(1996) [PubMed: 8900228] [Abstract]
Cited for: VARIANTS GA1 ARG-101; PRO-283; THR-293; LEU-305; ARG-390 AND ILE-416.
[13]"Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH)."
Keyser B., Muehlhausen C., Dickmanns A., Christensen E., Muschol N., Ullrich K., Braulke T.
Hum. Mol. Genet. 17:3854-3863(2008) [PubMed: 18775954] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS GA1 GLY-138; TRP-402 AND LYS-414, SUBUNIT.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

U69141 mRNA. Translation: AAB08455.1.
AF012342 expand/collapse EMBL AC list , AF012339, AF012340, AF012341 Genomic DNA. Translation: AAC52079.1.
BT006706 mRNA. Translation: AAP35352.1.
AD000092 Genomic DNA. Translation: AAB51174.1.
BC002579 mRNA. Translation: AAH02579.1.
IPIIPI00024317.
IPI00218112.
PIRT44260.
T45073.
RefSeqNP_000150.1.
NP_039663.1.
UniGeneHs.532699

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1SIQX-ray2.10A47-438[»]
1SIRX-ray2.60A45-438[»]
2R0MX-ray2.70A45-438[»]
2R0NX-ray2.30A45-438[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ92947. 2 interactions.

Proteomic databases

PRIDEQ92947.

Genome annotation databases

EnsemblENSG00000105607. Homo sapiens. [Contig view]
GeneID2639.
KEGGhsa:2639.
NMPDRfig|9606.3.peg.15791.

Organism-specific databases

GeneCardsGC19P012863.
H-InvDBHIX0014810.
HGNCHGNC:4189. GCDH.
MIM231670. phenotype.
608801. gene.
Orphanet25. Glutaryl-CoA dehydrogenase deficiency.
PharmGKBPA28604.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ92947.
HOVERGENQ92947.
OMAQ92947. KARYGIA.

Enzyme and pathway databases

BRENDA1.3.99.7. 247.
ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressQ92947.
BgeeQ92947.
CleanExHS_GCDH.
GermOnlineENSG00000105607. Homo sapiens.

Family and domain databases

InterProIPR006089. Acyl-CoA_DH_CS.
IPR006092. Acyl-CoA_DH_N.
IPR006090. Acyl-CoA_Oxase/DH_1.
IPR006091. Acyl-CoA_Oxase/DH_M.
IPR013786. AcylCoA_DH/ox_N.
IPR013764. AcylCoA_oxidase/DH_1/2_C.
[Graphical view]
Gene3DG3DSA:2.40.110.10. Acyl_CoA_DH/ox_M. 1 hit.
G3DSA:1.10.540.10. AcylCoA_DH/ox_N. 1 hit.
G3DSA:1.20.140.10. AcylCoA_DH_1/2_C. 1 hit.
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio10404.
SOURCESearch...

Entry information

Entry nameGCDH_HUMAN
AccessionPrimary (citable) accession number: Q92947
Secondary accession number(s): O14719
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents