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IPR015527

Description

IPR015527 is a Peptidase C26, gamma-glutamyl hydrolase.

<p>Gamma-glutamyl hydrolase (GH) is a lysosomal and secreted glycoprotein that hydrolyses the gamma-glutamyl tail of antifolate and folate polyglutamates. Tumour cells that have high levels of GH are inherently resistant to classical antifolates, and further resistance can be acquired by elevations in GH following exposure to this class of anti-tumour agents. The highest level of expression in normal tissues occurs in the liver and kidney in humans. GH is a low-affinity (micromolar), high-turnover enzyme that has a cysteine at the active site. GH is being evaluated as an intracellular target for inhibition in order to enhance the therapeutic activity of antifolates and fluorouracil [[cite:PUB00034829]].</p> <p>The 3-dimensional structure of GH shows a central eight-stranded β-sheet, which is sandwiched by three and five α-helices on each side (see [[cite:PUB00015219]]. The fold resembles that of glutamine amidotransferases (GATase) of class I, which are characterised by a conserved Cys-His-Glu active site. The major differences consist of extensions in four loops and at the C terminus of GGH. The active site residues are well conserved and the catalytically essential cysteine, positioned at a nucleophile elbow, suggests that GGH is a cysteine peptidase.</p>

This description is obtained from EB-eye REST.

Associated GO terms

GO predictions are based solely on the InterPro-to-GO mappings published by EMBL-EBI, which are in turn based on the mapping of predicted domains to the InterPro dataset. The InterPro-to-GO mapping was last updated on , while the GO metadata was last updated on .

GO term Namespace Name Definition Relationships
Molecular function Omega peptidase activity Catalysis of the removal of terminal peptide residues that are substituted, cyclized or linked by isopeptide bonds (peptide linkages other than those of alpha-carboxyl to alpha-amino groups).

Associated Lotus transcripts 4

Transcript Name Description Predicted domains Domain count
PREDICTED: gamma-glutamyl hydrolase-like [Glycine max] gi|356549636|ref|XP_003543198.1| 6
PREDICTED: gamma-glutamyl hydrolase-like [Glycine max] gi|356549636|ref|XP_003543198.1| 15
Gamma-glutamyl hydrolase; TAIR: AT1G78680.1 gamma-glutamyl hydrolase 2; Swiss-Prot: sp|O65355|GGH2_ARATH Gamma-glutamyl hydrolase 2; TrEMBL-Plants: tr|I3T794|I3T794_LOTJA Uncharacterized protein; Found in the gene: LotjaGi1g1v0441900 15
Gamma-glutamyl hydrolase; TAIR: AT1G78680.1 gamma-glutamyl hydrolase 2; Swiss-Prot: sp|O65355|GGH2_ARATH Gamma-glutamyl hydrolase 2; TrEMBL-Plants: tr|I3T794|I3T794_LOTJA Uncharacterized protein; Found in the gene: LotjaGi3g1v0262100 15

Co-occuring domains 1

A list of co-occurring predicted domains within the L. japonicus gene space:

Predicted domain Source Observations Saturation (%)
SignalP-noTM SignalP_GRAM_NEGATIVE 1 25.00