Gamma-glutamyl hydrolase

Gamma-glutamyl hydrolase is an enzyme[5][6][7][8] that catalyses the following chemical reaction:

Hydrolysis of a gamma-glutamyl bond

Gamma-glutamyl hydrolase
Identifiers
EC number	3.4.19.9
CAS number	9074-87-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

GGH
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1L9X
Identifiers
Aliases	GGH, GH, gamma-glutamyl hydrolase
External IDs	OMIM: 601509 MGI: 1329035 HomoloGene: 2881 GeneCards: GGH
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q12.3 Start 63,015,079 bp[1] End 63,038,806 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 A3 Start 20,042,052 bp[2] End 20,066,750 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • exopeptidase activity • omega peptidase activity • hydrolase activity • gamma-glutamyl-peptidase activity Cellular component • melanosome • cytosol • lysosome • extracellular exosome • cell nucleus • extracellular region • extracellular • azurophil granule lumen • specific granule lumen • tertiary granule lumen • vacuole Biological process • response to insulin • response to zinc ion • response to ethanol • response to drug • proteolysis • neutrophil degranulation • tetrahydrofolylpolyglutamate metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8836	14590
Ensembl	ENSG00000137563	ENSMUSG00000073987
UniProt	Q92820	Q9Z0L8
RefSeq (mRNA)	NM_003878	NM_010281
RefSeq (protein)	NP_003869	NP_034411
Location (UCSC)	Chr 8: 63.02 – 63.04 Mb	Chr 4: 20.04 – 20.07 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This lysosomal or secreted, thiol-dependent peptidase, most active at acidic pH.

In humans, gamma-glutamyl hydrolase is encoded by the GGH gene.[7][9][10] This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate.[10]

Nomenclature

Gamma-glutamyl hydrolase is also known as conjugase, folate conjugase, lysosomal gamma-glutamyl carboxypeptidase, gamma-Glu-X carboxypeptidase, pteroyl-poly-gamma-glutamate hydrolase, carboxypeptidase G, folic acid conjugase, poly(gamma-glutamic acid) endohydrolase, polyglutamate hydrolase, poly(glutamic acid) hydrolase II, pteroylpoly-gamma-glutamyl hydrolase.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.[§ 1]

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|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

References

1. GRCh38: Ensembl release 89: ENSG00000137563 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000073987 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wang Y, Nimec Z, Ryan TJ, Dias JA, Galivan J (August 1993). "The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells". Biochim. Biophys. Acta. 1164 (3): 227–35. doi:10.1016/0167-4838(93)90253-n. PMID 8343522.
6. Yao R, Rhee MS, Galivan J (September 1995). "Effects of gamma-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells". Mol. Pharmacol. 48 (3): 505–11. PMID 7565632.
7. Yao R, Schneider E, Ryan TJ, Galivan J (September 1996). "Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10134–8. doi:10.1073/pnas.93.19.10134. PMC 38349. PMID 8816764.
8. Yao R, Nimec Z, Ryan TJ, Galivan J (April 1996). "Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase". J. Biol. Chem. 271 (15): 8525–8. doi:10.1074/jbc.271.15.8525. PMID 8621474.
9. Yin D, Chave KJ, Macaluso CR, Galivan J, Yao R (Dec 1999). "Structural organization of the human gamma-glutamyl hydrolase gene". Gene. 238 (2): 463–70. doi:10.1016/S0378-1119(99)00362-5. PMID 10570974.
10. "Entrez Gene: GGH gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)".

Further reading

• Galivan J, Ryan T, Rhee M, et al. (1999). "Glutamyl hydrolase: properties and pharmacologic impact". Semin. Oncol. 26 (2 Suppl 6): 33–7. PMID 10598552.
• O'Connor BM, Rotundo RF, Nimec Z, et al. (1991). "Secretion of gamma-glutamyl hydrolase in vitro". Cancer Res. 51 (15): 3874–81. PMID 1713122.
• Chandler CJ, Wang TT, Halsted CH (1986). "Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization". J. Biol. Chem. 261 (2): 928–33. PMID 2867095.
• Wang TT, Chandler CJ, Halsted CH (1986). "Intracellular pteroylpolyglutamate hydrolase from human jejunal mucosa. Isolation and characterization". J. Biol. Chem. 261 (29): 13551–5. PMID 3759978.
• Yao R, Nimec Z, Ryan TJ, Galivan J (1996). "Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase". J. Biol. Chem. 271 (15): 8525–8. doi:10.1074/jbc.271.15.8525. PMID 8621474.
• Rhee MS, Lindau-Shepard B, Chave KJ, et al. (1998). "Characterization of human cellular gamma-glutamyl hydrolase". Mol. Pharmacol. 53 (6): 1040–6. PMID 9614206.
• Li H, Ryan TJ, Chave KJ, Van Roey P (2002). "Three-dimensional structure of human gamma -glutamyl hydrolase. A class I glatamine amidotransferase adapted for a complex substate". J. Biol. Chem. 277 (27): 24522–9. doi:10.1074/jbc.M202020200. PMID 11953431.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Basrur V, Yang F, Kushimoto T, et al. (2003). "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins". J. Proteome Res. 2 (1): 69–79. doi:10.1021/pr025562r. PMID 12643545.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• He P, Varticovski L, Bowman ED, et al. (2004). "Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray". Hum. Pathol. 35 (10): 1196–209. doi:10.1016/j.humpath.2004.06.014. PMID 15492986.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Eisele LE, Chave KJ, Lehning AC, Ryan TJ (2006). "Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer". Biochim. Biophys. Acta. 1764 (9): 1479–86. doi:10.1016/j.bbapap.2006.06.008. PMID 16945597.
• Chi A, Valencia JC, Hu ZZ, et al. (2007). "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes". J. Proteome Res. 5 (11): 3135–44. doi:10.1021/pr060363j. PMID 17081065.
• Hayashi H, Fujimaki C, Inoue K, et al. (2007). "Genetic polymorphism of C452T (T127I) in human gamma-glutamyl hydrolase in a Japanese population". Biol. Pharm. Bull. 30 (4): 839–41. doi:10.1248/bpb.30.839. PMID 17409534.

External links

• Gamma-glutamyl+hydrolase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q92820 (Gamma-glutamyl hydrolase) at the PDBe-KB.