Glutaryl-CoA dehydrogenase, mitochondrial

Details

Name
Glutaryl-CoA dehydrogenase, mitochondrial
Synonyms
  • 1.3.8.6
  • GCD
Gene Name
GCDH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0003805|Glutaryl-CoA dehydrogenase, mitochondrial
MALRGVSVRLLSRGPGLHVLRTWVSSAAQTEKGGRTQSQLAKSSRPEFDWQDPLVLEEQL
TTDEILIRDTFRTYCQERLMPRILLANRNEVFHREIISEMGELGVLGPTIKGYGCAGVSS
VAYGLLARELERVDSGYRSAMSVQSSLVMHPIYAYGSEEQRQKYLPQLAKGELLGCFGLT
EPNSGSDPSSMETRAHYNSSNKSYTLNGTKTWITNSPMADLFVVWARCEDGCIRGFLLEK
GMRGLSAPRIQGKFSLRASATGMIIMDGVEVPEENVLPGASSLGGPFGCLNNARYGIAWG
VLGASEFCLHTARQYALDRMQFGVPLARNQLIQKKLADMLTEITLGLHACLQLGRLKDQD
KAAPEMVSLLKRNNCGKALDIARQARDMLGGNGISDEYHVIRHAMNLEAVNTYEGTHDIH
ALILGRAITGIQAFTASK
Number of residues
438
Molecular Weight
48126.715
Theoretical pI
8.15
GO Classification
Functions
electron carrier activity / fatty-acyl-CoA binding / flavin adenine dinucleotide binding / glutaryl-CoA dehydrogenase activity / oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor
Processes
cellular nitrogen compound metabolic process / fatty acid beta-oxidation using acyl-CoA dehydrogenase / fatty-acyl-CoA biosynthetic process / lipid homeostasis / lysine catabolic process / small molecule metabolic process / tryptophan metabolic process
Components
mitochondrial inner membrane / mitochondrial matrix / mitochondrion
General Function
Oxidoreductase activity, acting on the ch-ch group of donors, with a flavin as acceptor
Specific Function
Catalyzes 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 Regions
Not Available
Cellular Location
Mitochondrion 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
Chromosome Location
19
Locus
19p13.2
External Identifiers
ResourceLink
UniProtKB IDQ92947
UniProtKB Entry NameGCDH_HUMAN
GenBank Protein ID1549327
GenBank Gene IDU69141
GenAtlas IDGCDH
HGNC IDHGNC:4189
General References
  1. Goodman SI, Kratz LE, Frerman FE: Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. Prog Clin Biol Res. 1992;375:169-73. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB03245S-4-Nitrobutyryl-CoAexperimentalunknownDetails