Details of the Target

General Information of Target

Target ID LDTP09886
Target Name Gamma-glutamyl hydrolase (GGH)
Gene Name GGH
Gene ID 8836
Synonyms
Gamma-glutamyl hydrolase; EC 3.4.19.9; Conjugase; GH; Gamma-Glu-X carboxypeptidase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MHCERFLCILRIIGTTLFGVSLLLGITAAYIVGYQFIQTDNYYFSFGLYGAFLASHLIIQ
SLFAFLEHRKMKKSLETPIKLNKTVALCIAAYQEDPDYLRKCLQSVKRLTYPGIKVVMVI
DGNSEDDLYMMDIFSEVMGRDKSATYIWKNNFHEKGPGETDESHKESSQHVTQLVLSNKS
ICIMQKWGGKREVMYTAFRALGRSVDYVQVCDSDTMLDPASSVEMVKVLEEDPMVGGVGG
DVQILNKYDSWISFLSSVRYWMAFNIERACQSYFGCVQCISGPLGMYRNSLLHEFVEDWY
NQEFMGNQCSFGDDRHLTNRVLSLGYATKYTARSKCLTETPIEYLRWLNQQTRWSKSYFR
EWLYNAMWFHKHHLWMTYEAIITGFFPFFLIATVIQLFYRGKIWNILLFLLTVQLVGLIK
SSFASCLRGNIVMVFMSLYSVLYMSSLLPAKMFAIATINKAGWGTSGRKTIVVNFIGLIP
VSVWFTILLGGVIFTIYKESKRPFSESKQTVLIVGTLLYACYWVMLLTLYVVLINKCGRR
KKGQQYDMVLDV
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Peptidase C26 family
Subcellular location
Secreted, extracellular space
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.
TTD ID
T71646
Uniprot ID
Q92820
DrugMap ID
TTZJRL0
Ensemble ID
ENST00000260118.7
HGNC ID
HGNC:4248
ChEMBL ID
CHEMBL2223

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 16 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
Alkylaryl probe 1
 Probe Info  		5.00  LDD0387  [2]
C-Sul
 Probe Info  		10.38  LDD0066  [3]
STPyne
 Probe Info  		K287(10.00); K49(1.16)  LDD0277  [4]
Probe 1
 Probe Info  		Y55(10.70)  LDD3495  [5]
P11
 Probe Info  		20.00  LDD0201  [6]
FBPP2
 Probe Info  		2.29  LDD0054  [7]
Acrolein
 Probe Info  		N.A.  LDD0221  [8]
DBIA
 Probe Info  		C314(0.91)  LDD1507  [9]
ATP probe
 Probe Info  		N.A.  LDD0199  [10]
1d-yne
 Probe Info  		N.A.  LDD0358  [11]
NHS
 Probe Info  		K253(0.00); K212(0.00)  LDD0010  [12]
Phosphinate-6
 Probe Info  		N.A.  LDD0018  [13]
1c-yne
 Probe Info  		N.A.  LDD0228  [11]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [8]
AOyne
 Probe Info  		12.90  LDD0443  [14]
PAL-AfBPP Probe
Click To Hide/Show 26 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C045
 Probe Info  		5.90  LDD1744  [15]
C149
 Probe Info  		6.50  LDD1830  [15]
C170
 Probe Info  		29.24  LDD1850  [15]
C171
 Probe Info  		6.59  LDD1851  [15]
C184
 Probe Info  		6.54  LDD1862  [15]
C186
 Probe Info  		13.18  LDD1864  [15]
C197
 Probe Info  		8.00  LDD1873  [15]
C208
 Probe Info  		9.65  LDD1883  [15]
C223
 Probe Info  		10.06  LDD1897  [15]
C237
 Probe Info  		6.96  LDD1910  [15]
C277
 Probe Info  		7.89  LDD1947  [15]
C281
 Probe Info  		6.11  LDD1951  [15]
C302
 Probe Info  		6.36  LDD1971  [15]
C310
 Probe Info  		14.42  LDD1977  [15]
C425
 Probe Info  		13.45  LDD2080  [15]
FFF probe11
 Probe Info  		14.12  LDD0471  [16]
FFF probe12
 Probe Info  		20.00  LDD0473  [16]
FFF probe13
 Probe Info  		20.00  LDD0475  [16]
FFF probe14
 Probe Info  		20.00  LDD0477  [16]
FFF probe15
 Probe Info  		5.39  LDD0478  [16]
FFF probe2
 Probe Info  		5.88  LDD0463  [16]
FFF probe3
 Probe Info  		7.04  LDD0464  [16]
FFF probe9
 Probe Info  		20.00  LDD0470  [16]
JN0003
 Probe Info  		20.00  LDD0469  [16]
VE-P
 Probe Info  		N.A.  LDD0396  [17]
OEA-DA
 Probe Info  		7.50  LDD0046  [18]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C314(0.91)  LDD1507  [9]
 LDCM0226  AC11 HEK-293T C314(0.86)  LDD1509  [9]
 LDCM0259  AC14 HEK-293T C314(0.86)  LDD1512  [9]
 LDCM0276  AC17 HEK-293T C314(0.88)  LDD1515  [9]
 LDCM0278  AC19 HEK-293T C314(0.70)  LDD1517  [9]
 LDCM0281  AC21 HEK-293T C314(0.90)  LDD1520  [9]
 LDCM0282  AC22 HEK-293T C314(0.88)  LDD1521  [9]
 LDCM0284  AC24 HEK-293T C314(1.06)  LDD1523  [9]
 LDCM0285  AC25 HEK-293T C314(0.89)  LDD1524  [9]
 LDCM0287  AC27 HEK-293T C314(1.00)  LDD1526  [9]
 LDCM0289  AC29 HEK-293T C314(0.98)  LDD1528  [9]
 LDCM0290  AC3 HEK-293T C314(0.82)  LDD1529  [9]
 LDCM0291  AC30 HEK-293T C314(0.68)  LDD1530  [9]
 LDCM0293  AC32 HEK-293T C314(0.94)  LDD1532  [9]
 LDCM0294  AC33 HEK-293T C314(1.09)  LDD1533  [9]
 LDCM0296  AC35 HEK-293T C314(1.11)  LDD1535  [9]
 LDCM0298  AC37 HEK-293T C314(1.27)  LDD1537  [9]
 LDCM0299  AC38 HEK-293T C314(0.95)  LDD1538  [9]
 LDCM0302  AC40 HEK-293T C314(0.83)  LDD1541  [9]
 LDCM0303  AC41 HEK-293T C314(0.96)  LDD1542  [9]
 LDCM0305  AC43 HEK-293T C314(0.88)  LDD1544  [9]
 LDCM0307  AC45 HEK-293T C314(0.93)  LDD1546  [9]
 LDCM0308  AC46 HEK-293T C314(0.64)  LDD1547  [9]
 LDCM0310  AC48 HEK-293T C314(0.95)  LDD1549  [9]
 LDCM0311  AC49 HEK-293T C314(0.75)  LDD1550  [9]
 LDCM0312  AC5 HEK-293T C314(0.76)  LDD1551  [9]
 LDCM0314  AC51 HEK-293T C314(0.88)  LDD1553  [9]
 LDCM0316  AC53 HEK-293T C314(0.85)  LDD1555  [9]
 LDCM0317  AC54 HEK-293T C314(0.93)  LDD1556  [9]
 LDCM0319  AC56 HEK-293T C314(1.01)  LDD1558  [9]
 LDCM0320  AC57 HEK-293T C314(0.88)  LDD1559  [9]
 LDCM0322  AC59 HEK-293T C314(0.75)  LDD1561  [9]
 LDCM0323  AC6 HEK-293T C314(0.68)  LDD1562  [9]
 LDCM0325  AC61 HEK-293T C314(0.85)  LDD1564  [9]
 LDCM0326  AC62 HEK-293T C314(0.78)  LDD1565  [9]
 LDCM0328  AC64 HEK-293T C314(1.12)  LDD1567  [9]
 LDCM0345  AC8 HEK-293T C314(0.91)  LDD1569  [9]
 LDCM0248  AKOS034007472 HEK-293T C314(1.06)  LDD1511  [9]
 LDCM0356  AKOS034007680 HEK-293T C314(0.99)  LDD1570  [9]
 LDCM0275  AKOS034007705 HEK-293T C314(1.03)  LDD1514  [9]
 LDCM0156  Aniline NCI-H1299 12.13  LDD0403  [1]
 LDCM0088  C45 HEK-293T 20.00  LDD0201  [6]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [8]
 LDCM0367  CL1 HEK-293T C314(1.22)  LDD1571  [9]
 LDCM0368  CL10 HEK-293T C314(0.83)  LDD1572  [9]
 LDCM0370  CL101 HEK-293T C314(1.06)  LDD1574  [9]
 LDCM0372  CL103 HEK-293T C314(1.10)  LDD1576  [9]
 LDCM0374  CL105 HEK-293T C314(0.93)  LDD1578  [9]
 LDCM0376  CL107 HEK-293T C314(0.94)  LDD1580  [9]
 LDCM0378  CL109 HEK-293T C314(1.47)  LDD1582  [9]
 LDCM0381  CL111 HEK-293T C314(1.30)  LDD1585  [9]
 LDCM0383  CL113 HEK-293T C314(1.41)  LDD1587  [9]
 LDCM0385  CL115 HEK-293T C314(1.08)  LDD1589  [9]
 LDCM0387  CL117 HEK-293T C314(0.95)  LDD1591  [9]
 LDCM0389  CL119 HEK-293T C314(1.21)  LDD1593  [9]
 LDCM0390  CL12 HEK-293T C314(0.94)  LDD1594  [9]
 LDCM0392  CL121 HEK-293T C314(0.95)  LDD1596  [9]
 LDCM0394  CL123 HEK-293T C314(1.26)  LDD1598  [9]
 LDCM0396  CL125 HEK-293T C314(1.57)  LDD1600  [9]
 LDCM0398  CL127 HEK-293T C314(1.20)  LDD1602  [9]
 LDCM0400  CL13 HEK-293T C314(1.03)  LDD1604  [9]
 LDCM0402  CL15 HEK-293T C314(1.02)  LDD1606  [9]
 LDCM0404  CL17 HEK-293T C314(1.07)  LDD1608  [9]
 LDCM0406  CL19 HEK-293T C314(1.04)  LDD1610  [9]
 LDCM0409  CL21 HEK-293T C314(0.95)  LDD1613  [9]
 LDCM0410  CL22 HEK-293T C314(0.68)  LDD1614  [9]
 LDCM0412  CL24 HEK-293T C314(0.92)  LDD1616  [9]
 LDCM0413  CL25 HEK-293T C314(1.31)  LDD1617  [9]
 LDCM0415  CL27 HEK-293T C314(0.92)  LDD1619  [9]
 LDCM0417  CL29 HEK-293T C314(0.84)  LDD1621  [9]
 LDCM0418  CL3 HEK-293T C314(1.00)  LDD1622  [9]
 LDCM0420  CL31 HEK-293T C314(0.82)  LDD1624  [9]
 LDCM0422  CL33 HEK-293T C314(0.73)  LDD1626  [9]
 LDCM0423  CL34 HEK-293T C314(0.71)  LDD1627  [9]
 LDCM0425  CL36 HEK-293T C314(1.01)  LDD1629  [9]
 LDCM0426  CL37 HEK-293T C314(0.93)  LDD1630  [9]
 LDCM0428  CL39 HEK-293T C314(1.28)  LDD1632  [9]
 LDCM0431  CL41 HEK-293T C314(0.87)  LDD1635  [9]
 LDCM0433  CL43 HEK-293T C314(0.98)  LDD1637  [9]
 LDCM0435  CL45 HEK-293T C314(0.73)  LDD1639  [9]
 LDCM0436  CL46 HEK-293T C314(0.63)  LDD1640  [9]
 LDCM0438  CL48 HEK-293T C314(1.14)  LDD1642  [9]
 LDCM0439  CL49 HEK-293T C314(0.76)  LDD1643  [9]
 LDCM0440  CL5 HEK-293T C314(1.08)  LDD1644  [9]
 LDCM0444  CL53 HEK-293T C314(0.96)  LDD1647  [9]
 LDCM0446  CL55 HEK-293T C314(1.03)  LDD1649  [9]
 LDCM0448  CL57 HEK-293T C314(0.91)  LDD1651  [9]
 LDCM0449  CL58 HEK-293T C314(0.75)  LDD1652  [9]
 LDCM0452  CL60 HEK-293T C314(1.04)  LDD1655  [9]
 LDCM0453  CL61 HEK-293T C314(1.20)  LDD1656  [9]
 LDCM0455  CL63 HEK-293T C314(1.20)  LDD1658  [9]
 LDCM0457  CL65 HEK-293T C314(0.90)  LDD1660  [9]
 LDCM0459  CL67 HEK-293T C314(0.88)  LDD1662  [9]
 LDCM0461  CL69 HEK-293T C314(0.79)  LDD1664  [9]
 LDCM0462  CL7 HEK-293T C314(0.87)  LDD1665  [9]
 LDCM0463  CL70 HEK-293T C314(0.83)  LDD1666  [9]
 LDCM0465  CL72 HEK-293T C314(0.98)  LDD1668  [9]
 LDCM0466  CL73 HEK-293T C314(1.10)  LDD1669  [9]
 LDCM0470  CL77 HEK-293T C314(0.96)  LDD1673  [9]
 LDCM0472  CL79 HEK-293T C314(0.91)  LDD1675  [9]
 LDCM0475  CL81 HEK-293T C314(0.76)  LDD1678  [9]
 LDCM0476  CL82 HEK-293T C314(0.68)  LDD1679  [9]
 LDCM0478  CL84 HEK-293T C314(0.77)  LDD1681  [9]
 LDCM0479  CL85 HEK-293T C314(1.19)  LDD1682  [9]
 LDCM0481  CL87 HEK-293T C314(1.00)  LDD1684  [9]
 LDCM0483  CL89 HEK-293T C314(0.91)  LDD1686  [9]
 LDCM0484  CL9 HEK-293T C314(0.92)  LDD1687  [9]
 LDCM0486  CL91 HEK-293T C314(0.78)  LDD1689  [9]
 LDCM0488  CL93 HEK-293T C314(1.03)  LDD1691  [9]
 LDCM0489  CL94 HEK-293T C314(1.17)  LDD1692  [9]
 LDCM0491  CL96 HEK-293T C314(0.81)  LDD1694  [9]
 LDCM0492  CL97 HEK-293T C314(1.35)  LDD1695  [9]
 LDCM0494  CL99 HEK-293T C314(1.09)  LDD1697  [9]
 LDCM0185  Compound 17 HEK-293T 6.49  LDD0512  [16]
 LDCM0191  Compound 21 HEK-293T 3.89  LDD0508  [16]
 LDCM0190  Compound 34 HEK-293T 3.81  LDD0510  [16]
 LDCM0193  Compound 36 HEK-293T 4.07  LDD0511  [16]
 LDCM0495  E2913 HEK-293T C314(1.38)  LDD1698  [9]
 LDCM0468  Fragment33 HEK-293T C314(1.34)  LDD1671  [9]
 LDCM0107  IAA HeLa N.A.  LDD0221  [8]
 LDCM0109  NEM HeLa N.A.  LDD0226  [8]
 LDCM0099  Phenelzine MDA-MB-231 11.00  LDD0388  [2]
 LDCM0008  Tranylcypromine SH-SY5Y 2.29  LDD0054  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Small glutamine-rich tetratricopeptide repeat-containing protein beta (SGTB) SGT family Q96EQ0

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Folic Acid Small molecular drug DB00158
Methotrexate Small molecular drug DB00563

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
3 Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells. Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129. Epub 2022 Mar 4.
4 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
5 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
6 Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors. J Am Chem Soc. 2022 Mar 30;144(12):5377-5388. doi: 10.1021/jacs.1c12748. Epub 2022 Mar 2.
7 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
8 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
9 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
10 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
11 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
12 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
13 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
14 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
15 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
16 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
17 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
18 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570