You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NameGlutaryl-CoA dehydrogenase, mitochondrial
Synonyms
  • 1.3.8.6
  • GCD
Gene NameGCDH
OrganismHuman
Amino acid sequence
>lcl|BSEQ0003805|Glutaryl-CoA dehydrogenase, mitochondrial
MALRGVSVRLLSRGPGLHVLRTWVSSAAQTEKGGRTQSQLAKSSRPEFDWQDPLVLEEQL
TTDEILIRDTFRTYCQERLMPRILLANRNEVFHREIISEMGELGVLGPTIKGYGCAGVSS
VAYGLLARELERVDSGYRSAMSVQSSLVMHPIYAYGSEEQRQKYLPQLAKGELLGCFGLT
EPNSGSDPSSMETRAHYNSSNKSYTLNGTKTWITNSPMADLFVVWARCEDGCIRGFLLEK
GMRGLSAPRIQGKFSLRASATGMIIMDGVEVPEENVLPGASSLGGPFGCLNNARYGIAWG
VLGASEFCLHTARQYALDRMQFGVPLARNQLIQKKLADMLTEITLGLHACLQLGRLKDQD
KAAPEMVSLLKRNNCGKALDIARQARDMLGGNGISDEYHVIRHAMNLEAVNTYEGTHDIH
ALILGRAITGIQAFTASK
Number of residues438
Molecular Weight48126.715
Theoretical pI8.15
GO Classification
Functions
  • electron carrier activity
  • flavin adenine dinucleotide binding
  • fatty-acyl-CoA binding
  • oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor
  • glutaryl-CoA dehydrogenase activity
Processes
  • cellular nitrogen compound metabolic process
  • small molecule metabolic process
  • lysine catabolic process
  • fatty acid beta-oxidation using acyl-CoA dehydrogenase
  • lipid homeostasis
  • tryptophan metabolic process
  • fatty-acyl-CoA biosynthetic process
Components
  • mitochondrial matrix
  • mitochondrion
  • mitochondrial inner membrane
General FunctionOxidoreductase activity, acting on the ch-ch group of donors, with a flavin as acceptor
Specific FunctionCatalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. Isoform Short is inactive.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1549327
UniProtKB IDQ92947
UniProtKB Entry NameGCDH_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0019200|Glutaryl-CoA dehydrogenase, mitochondrial (GCDH)
ATGGCCCTGAGAGGCGTCTCCGTGCGGCTGCTGAGCCGCGGACCCGGCCTGCACGTCCTT
CGCACGTGGGTCTCGTCGGCGGCGCAGACCGAGAAAGGCGGGAGAACACAGAGCCAACTG
GCTAAGTCCTCGCGTCCCGAGTTTGACTGGCAGGACCCGCTGGTGCTGGAGGAGCAGCTG
ACCACAGATGAGATCCTCATCAGGGACACCTTCCGCACCTACTGCCAGGAGAGACTCATG
CCTCGCATCCTGTTGGCCAATCGCAACGAAGTTTTTCATCGGGAGATCATTTCGGAGATG
GGGGAGTTGGGTGTGCTGGGCCCCACCATCAAAGGATATGGCTGTGCTGGGGTTTCGTCT
GTGGCCTATGGGCTCCTGGCCCGAGAGCTGGAGCGGGTGGACAGTGGCTACAGGTCGGCG
ATGAGTGTCCAGTCCTCCCTCGTCATGCACCCTATCTATGCCTATGGCAGCGAGGAACAG
CGGCAGAAGTACCTGCCCCAGCTGGCCAAGGGGGAGCTCCTGGGCTGCTTCGGGCTCACA
GAGCCCAACAGCGGAAGTGACCCCAGCAGCATGGAGACCAGAGCCCACTACAACTCATCC
AACAAGAGCTACACCCTCAATGGGACCAAGACCTGGATCACGAACTCGCCTATGGCCGAT
CTGTTTGTAGTGTGGGCTCGGTGTGAAGATGGCTGCATTCGGGGCTTCCTGCTGGAGAAG
GGGATGCGGGGTCTCTCGGCCCCCAGGATCCAGGGCAAGTTCTCGCTGCGGGCCTCAGCC
ACAGGCATGATCATCATGGACGGTGTGGAGGTGCCAGAGGAGAATGTGCTCCCTGGTGCA
TCCAGCCTGGGGGGTCCCTTCGGCTGCCTGAACAACGCCCGGTACGGCATCGCGTGGGGC
GTGCTTGGAGCTTCGGAGTTCTGCTTGCACACAGCCCGGCAGTACGCCCTCGACAGGATG
CAGTTTGGTGTCCCACTGGCCAGGAACCAGCTGATTCAGAAGAAGCTGGCAGACATGCTC
ACTGAGATTACCCTGGGCCTTCACGCCTGCCTGCAGCTCGGCCGCTTGAAGGACCAGGAC
AAGGCTGCCCCCGAGATGGTTTCTCTGCTGAAGAGGAATAACTGTGGGAAAGCCCTGGAC
ATCGCCCGCCAGGCCCGAGACATGCTGGGGGGGAATGGGATTTCTGACGAGTATCACGTG
ATCCGGCACGCCATGAACCTGGAGGCCGTGAACACCTACGAAGGTACACATGACATTCAC
GCCCTGATCCTTGGGAGAGCTATCACGGGAATCCAGGCGTTCACGGCCAGCAAGTGA
GenBank Gene IDU69141
GeneCard IDNot Available
GenAtlas IDGCDH
HGNC IDHGNC:4189
Chromosome Location19
Locus19p13.2
References
  1. Goodman SI, Kratz LE, Frerman FE: Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. Prog Clin Biol Res. 1992;375:169-73. 1438360
  2. Goodman SI, Kratz LE, DiGiulio KA, Biery BJ, Goodman KE, Isaya G, Frerman FE: Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli. Hum Mol Genet. 1995 Sep;4(9):1493-8. 8541831
  3. Schwartz M, Christensen E, Superti-Furga A, Brandt NJ: The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I. Hum Genet. 1998 Apr;102(4):452-8. 9600243
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, 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, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, 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 SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, 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 TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Hyman DB, Tanaka K: Specific glutaryl-CoA dehydrogenating activity is deficient in cultured fibroblasts from glutaric aciduria patients. J Clin Invest. 1984 Mar;73(3):778-84. 6423663
  8. Goodman SI, Stein DE, Schlesinger S, Christensen E, Schwartz M, Greenberg CR, Elpeleg ON: Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations. Hum Mutat. 1998;12(3):141-4. 9711871
  9. Rao KS, Albro M, Dwyer TM, Frerman FE: Kinetic mechanism of glutaryl-CoA dehydrogenase. Biochemistry. 2006 Dec 26;45(51):15853-61. Epub 2006 Dec 2. 17176108
  10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  12. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  13. Fu Z, Wang M, Paschke R, Rao KS, Frerman FE, Kim JJ: Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions. Biochemistry. 2004 Aug 3;43(30):9674-84. 15274622
  14. Rao KS, Fu Z, Albro M, Narayanan B, Baddam S, Lee HJ, Kim JJ, Frerman FE: The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate. Biochemistry. 2007 Dec 18;46(50):14468-77. Epub 2007 Nov 17. 18020372
  15. Biery BJ, Stein DE, Morton DH, Goodman SI: 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. Am J Hum Genet. 1996 Nov;59(5):1006-11. 8900227
  16. Anikster Y, Shaag A, Joseph A, Mandel H, Ben-Zeev B, Christensen E, Elpeleg ON: Glutaric aciduria type I in the Arab and Jewish communities in Israel. Am J Hum Genet. 1996 Nov;59(5):1012-8. 8900228
  17. Muhlhausen C, Christensen E, Schwartz M, Muschol N, Ullrich K, Lukacs Z: Severe phenotype despite high residual glutaryl-CoA dehydrogenase activity: a novel mutation in a Turkish patient with glutaric aciduria type I. J Inherit Metab Dis. 2003;26(7):713-4. 14707522
  18. Keyser B, Muhlhausen C, Dickmanns A, Christensen E, Muschol N, Ullrich K, Braulke T: Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH). Hum Mol Genet. 2008 Dec 15;17(24):3854-63. doi: 10.1093/hmg/ddn284. Epub 2008 Sep 5. 18775954
  19. Georgiou T, Nicolaidou P, Hadjichristou A, Ioannou R, Dionysiou M, Siama E, Chappa G, Anastasiadou V, Drousiotou A: Molecular analysis of Cypriot patients with Glutaric aciduria type I: identification of two novel mutations. Clin Biochem. 2014 Sep;47(13-14):1300-5. doi: 10.1016/j.clinbiochem.2014.06.017. Epub 2014 Jun 25. 24973495