Target Information
| Target General Information | Top | |||||
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| Target ID |
T54316
(Former ID: TTDNR00680)
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| Target Name |
Glucose-6-phosphate isomerase (GPI)
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| Synonyms |
Sperm antigen 36; SA-36; Phosphohexose isomerase; Phosphoglucose isomerase; PHI; PGI; Neuroleukin; NLK; GPI; Autocrine motility factor; AMF
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| Gene Name |
GPI
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Besides it's role as a glycolytic enzyme, mammalian GPI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. GPI is also a neurotrophic factor (Neuroleukin) for spinal and sensory neurons.
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| BioChemical Class |
Intramolecular oxidoreductases
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| UniProt ID | ||||||
| EC Number |
EC 5.3.1.9
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| Sequence |
MAALTRDPQFQKLQQWYREHRSELNLRRLFDANKDRFNHFSLTLNTNHGHILVDYSKNLV
TEDVMRMLVDLAKSRGVEAARERMFNGEKINYTEGRAVLHVALRNRSNTPILVDGKDVMP EVNKVLDKMKSFCQRVRSGDWKGYTGKTITDVINIGIGGSDLGPLMVTEALKPYSSGGPR VWYVSNIDGTHIAKTLAQLNPESSLFIIASKTFTTQETITNAETAKEWFLQAAKDPSAVA KHFVALSTNTTKVKEFGIDPQNMFEFWDWVGGRYSLWSAIGLSIALHVGFDNFEQLLSGA HWMDQHFRTTPLEKNAPVLLALLGIWYINCFGCETHAMLPYDQYLHRFAAYFQQGDMESN GKYITKSGTRVDHQTGPIVWGEPGTNGQHAFYQLIHQGTKMIPCDFLIPVQTQHPIRKGL HHKILLANFLAQTEALMRGKSTEEARKELQAAGKSPEDLERLLPHKVFEGNRPTNSIVFT KLTPFMLGALVAMYEHKIFVQGIIWDINSFDQWGVELGKQLAKKIEPELDGSAQVTSHDA STNGLINFIKQQREARVQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T55A2Y | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Erythose-4-phosphate | Ligand Info | |||||
| Structure Description | Crystal structure of human autocrine motility factor complexed with an inhibitor | PDB:1IRI | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
MAALTRDPQF
10 QKLQQWYREH20 RSELNLRRLF30 DANKDRFNHF40 SLTLNTNHGH50 ILVDYSKNLV 60 TEDVMRMLVD70 LAKSRGVEAA80 RERMFNGEKI90 NYTEGRAVLH100 VALRNRSNTP 110 ILVDGKDVMP120 EVNKVLDKMK130 SFCQRVRSGD140 WKGYTGKTIT150 DVINIGIGGS 160 DLGPLMVTEA170 LKPYSSGGPR180 VWYVSNIDGT190 HIAKTLAQLN200 PESSLFIIAS 210 KTFTTQETIT220 NAETAKEWFL230 QAAKDPSAVA240 KHFVALSTNT250 TKVKEFGIDP 260 QNMFEFWDWV270 GGRYSLWSAI280 GLSIALHVGF290 DNFEQLLSGA300 HWMDQHFRTT 310 PLEKNAPVLL320 ALLGIWYINC330 FGCETHAMLP340 YDQYLHRFAA350 YFQQGDMESN 360 GKYITKSGTR370 VDHQTGPIVW380 GEPGTNGQHA390 FYQLIHQGTK400 MIPCDFLIPV 410 QTQHPIRKGL420 HHKILLANFL430 AQTEALMRGK440 STEEARKELQ450 AAGKSPEDLE 460 RLLPHKVFEG470 NRPTNSIVFT480 KLTPFMLGAL490 VAMYEHKIFV500 QGIIWDINSF 510 DQWGVELGKQ520 LAKKIEPELD530 GSAQVTSHDA540 STNGLINFIK550 QQREARV |
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| Ligand Name: 2,5,8,11,14,17-Hexaoxaoctadecane | Ligand Info | |||||
| Structure Description | Crystal structure of human phosphoglucose isomerase in complex with inhibitor | PDB:6XUI | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [3] |
| PDB Sequence |
AALTRDPQFQ
10 KLQQWYREHR20 SELNLRRLFD30 ANKDRFNHFS40 LTLNTNHGHI50 LVDYSKNLVT 60 EDVMRMLVDL70 AKSRGVEAAR80 ERMFNGEKIN90 YTEGRAVLHV100 ALRNRSNTPI 110 LVDGKDVMPE120 VNKVLDKMKS130 FCQRVRSGDW140 KGYTGKTITD150 VINIGIGGSD 160 LGPLMVTEAL170 KPYSSGGPRV180 WYVSNIDGTH190 IAKTLAQLNP200 ESSLFIIASK 210 TFTTQETITN220 AETAKEWFLQ230 AAKDPSAVAK240 HFVALSTNTT250 KVKEFGIDPQ 260 NMFEFWDWVG270 GRYSLWSAIG280 LSIALHVGFD290 NFEQLLSGAH300 WMDQHFRTTP 310 LEKNAPVLLA320 LLGIWYINCF330 GCETHAMLPY340 DQYLHRFAAY350 FQQGDMESNG 360 KYITKSGTRV370 DHQTGPIVWG380 EPGTNGQHAF390 YQLIHQGTKM400 IPCDFLIPVQ 410 TQHPIRKGLH420 HKILLANFLA430 QTEALMRGKS440 TEEARKELQA450 AGKSPEDLER 460 LLPHKVFEGN470 RPTNSIVFTK480 LTPFMLGALV490 AMYEHKIFVQ500 GIIWDINSFD 510 QWGVELGKQL520 AKKIEPELDG530 SAQVTSHDAS540 TNGLINFIKQ550 QREARV |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Glycolysis / Gluconeogenesis | hsa00010 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Pentose phosphate pathway | hsa00030 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Starch and sucrose metabolism | hsa00500 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Amino sugar and nucleotide sugar metabolism | hsa00520 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Degree | 40 | Degree centrality | 4.30E-03 | Betweenness centrality | 4.41E-03 |
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| Closeness centrality | 2.16E-01 | Radiality | 1.38E+01 | Clustering coefficient | 1.51E-01 |
| Neighborhood connectivity | 1.03E+01 | Topological coefficient | 7.81E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Molecular association of glucose-6-phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehydrogenase in cancer cells. BMC Cancer. 2016 Feb 24;16:152. | |||||
| REF 2 | Inhibition mechanism of cytokine activity of human autocrine motility factor examined by crystal structure analyses and site-directed mutagenesis studies. J Mol Biol. 2002 May 10;318(4):985-97. | |||||
| REF 3 | Novel N-substituted 5-phosphate-d-arabinonamide derivatives as strong inhibitors of phosphoglucose isomerases: Synthesis, structure-activity relationship and crystallographic studies. Bioorg Chem. 2020 Sep;102:104048. | |||||
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