Gamma-glutamyl hydrolase

Details

Name
Gamma-glutamyl hydrolase
Synonyms
  • 3.4.19.9
  • Conjugase
  • Gamma-Glu-X carboxypeptidase
  • GH
Gene Name
GGH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0018932|Gamma-glutamyl hydrolase
MASPGCLLCVLGLLLCGAASLELSRPHGDTAKKPIIGILMQKCRNKVMKNYGRYYIAASY
VKYLESAGARVVPVRLDLTEKDYEILFKSINGILFPGGSVDLRRSDYAKVAKIFYNLSIQ
SFDDGDYFPVWGTCLGFEELSLLISGECLLTATDTVDVAMPLNFTGGQLHSRMFQNFPTE
LLLSLAVEPLTANFHKWSLSVKNFTMNEKLKKFFNVLTTNTDGKIEFISTMEGYKYPVYG
VQWHPEKAPYEWKNLDGISHAPNAVKTAFYLAEFFVNEARKNNHHFKSESEEEKALIYQF
SPIYTGNISSFQQCYIFD
Number of residues
318
Molecular Weight
35964.045
Theoretical pI
7.14
GO Classification
Functions
exopeptidase activity / gamma-glutamyl-peptidase activity / omega peptidase activity
Processes
glutamine metabolic process / proteolysis / response to drug / response to ethanol / response to insulin / response to zinc ion / tetrahydrofolylpolyglutamate metabolic process
Components
cytosol / extracellular exosome / extracellular space / lysosome / melanosome / nucleus / vacuole
General Function
Omega peptidase activity
Specific Function
Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0018933|Gamma-glutamyl hydrolase (GGH)
ATGGCCAGTCCGGGCTGCCTGCTGTGCGTGCTGGGCCTGCTACTCTGCGGGGCGGCGAGC
CTCGAGCTGTCTAGACCCCACGGCGACACCGCCAAGAAGCCCATCATCGGAATATTAATG
CAAAAATGCCGTAATAAAGTCATGAAAAACTATGGAAGATACTATATTGCTGCGTCCTAT
GTAAAGTACTTGGAGTCTGCAGGTGCGAGAGTTGTACCAGTAAGGCTGGATCTTACAGAG
AAAGACTATGAAATACTTTTCAAATCTATTAATGGAATCCTTTTCCCTGGAGGAAGTGTT
GACCTCAGACGCTCAGATTATGCTAAAGTGGCCAAAATATTTTATAACTTGTCCATACAG
AGTTTTGATGATGGAGACTATTTTCCTGTGTGGGGCACATGCCTTGGATTTGAAGAGCTT
TCACTGCTGATTAGTGGAGAGTGCTTATTAACTGCCACAGATACTGTTGACGTGGCAATG
CCGCTGAACTTCACTGGAGGTCAATTGCACAGCAGAATGTTCCAGAATTTTCCTACTGAG
TTGTTGCTGTCATTAGCAGTAGAACCTCTGACTGCCAATTTCCATAAGTGGAGCCTCTCC
GTGAAGAATTTTACAATGAATGAAAAGTTAAAGAAGTTTTTCAATGTCTTAACTACAAAT
ACAGATGGCAAGATTGAGTTTATTTCAACAATGGAAGGATATAAGTATCCAGTATATGGT
GTCCAGTGGCATCCAGAGAAAGCACCTTATGAGTGGAAGAATTTGGATGGCATTTCCCAT
GCACCTAATGCTGTGAAAACCGCATTTTATTTAGCAGAGTTTTTTGTTAATGAAGCTCGG
AAAAACAACCATCATTTTAAATCTGAATCTGAAGAGGAGAAAGCATTGATTTATCAGTTC
AGTCCAATTTATACTGGAAATATTTCTTCATTTCAGCAATGTTACATATTTGATTGA
Chromosome Location
8
Locus
8q12.3
External Identifiers
ResourceLink
UniProtKB IDQ92820
UniProtKB Entry NameGGH_HUMAN
GenBank Protein ID2951931
GenBank Gene IDU55206
GenAtlas IDGGH
HGNC IDHGNC:4248
General References
  1. Yao R, Schneider E, Ryan TJ, Galivan J: Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10134-8. [PubMed:8816764]
  2. Yin D, Chave KJ, Macaluso CR, Galivan J, Yao R: Structural organization of the human gamma-glutamyl hydrolase gene. Gene. 1999 Oct 1;238(2):463-70. [PubMed:10570974]
  3. 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. [PubMed:15489334]
  4. Chave KJ, Galivan J, Ryan TJ: Site-directed mutagenesis establishes cysteine-110 as essential for enzyme activity in human gamma-glutamyl hydrolase. Biochem J. 1999 Nov 1;343 Pt 3:551-5. [PubMed:10527932]
  5. Chave KJ, Auger IE, Galivan J, Ryan TJ: Molecular modeling and site-directed mutagenesis define the catalytic motif in human gamma -glutamyl hydrolase. J Biol Chem. 2000 Dec 22;275(51):40365-70. [PubMed:11005824]
  6. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. [PubMed:12643545]
  7. Eisele LE, Chave KJ, Lehning AC, Ryan TJ: Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer. Biochim Biophys Acta. 2006 Sep;1764(9):1479-86. Epub 2006 Jul 12. [PubMed:16945597]
  8. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed:17081065]
  9. 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. [PubMed:21269460]
  10. 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. [PubMed:24275569]
  11. Li H, Ryan TJ, Chave KJ, Van Roey P: Three-dimensional structure of human gamma -glutamyl hydrolase. A class I glatamine amidotransferase adapted for a complex substate. J Biol Chem. 2002 Jul 5;277(27):24522-9. Epub 2002 Apr 12. [PubMed:11953431]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00158Folic Acidapproved, nutraceutical, vet_approvedunknownsubstrateDetails
DB00563MethotrexateapprovedunknownsubstrateDetails