Target Information
| Target General Information | Top | |||||
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| Target ID |
T05387
(Former ID: TTDC00120)
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| Target Name |
Tissue transglutaminase (TG2)
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| Synonyms |
Transglutaminase-2; Transglutaminase H; Transglutaminase C; Transglutaminase 2; Tranglutaminase 2; TTg; TGase-H; TGase-2; TGase H; TGase C; TGC; TG(C)Protein-glutamine gamma-glutamyltransferase; TG(C); Protein-glutamine gamma-glutamyltransferase 2
Click to Show/Hide
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| Gene Name |
TGM2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Kidney fibrosis [ICD-11: GC01] | |||||
| Function |
Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.2.13
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| Sequence |
MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS
VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSL IVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG LHKLVVNFESDKLKAVKGFRNVIIGPA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T26FBV | |||||
| Drugs and Modes of Action | Top | |||||
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| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | NTU281 | Drug Info | Preclinical | Renal fibrosis | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 55 Inhibitor drugs | + | ||||
| 1 | 2-alkyloxy-3-phenylethynyl-4a,5-dihydropyrido[2,3-b]pyrazine derivative 1 | Drug Info | [1] | |||
| 2 | 3-acylidene-2-oxoindole derivative 1 | Drug Info | [1] | |||
| 3 | 3-acylidene-2-oxoindole derivative 2 | Drug Info | [1] | |||
| 4 | Acyl piperidine derivative 2 | Drug Info | [1] | |||
| 5 | Acyl piperidine derivative 3 | Drug Info | [1] | |||
| 6 | Azachalcone derivative 1 | Drug Info | [1] | |||
| 7 | Benzotriazole derivative 1 | Drug Info | [1] | |||
| 8 | Chalcone derivative 5 | Drug Info | [1] | |||
| 9 | Chloroacetyl ester derivative 1 | Drug Info | [1] | |||
| 10 | Dihydroisoxazole derivative 1 | Drug Info | [1] | |||
| 11 | Dihydroisoxazole derivative 2 | Drug Info | [1] | |||
| 12 | Dipeptide analog 2 | Drug Info | [1] | |||
| 13 | Dipeptide analog 3 | Drug Info | [1] | |||
| 14 | Dipeptide analog 4 | Drug Info | [1] | |||
| 15 | Isothiocyanate derivative 1 | Drug Info | [1] | |||
| 16 | Peptide analog 52 | Drug Info | [1] | |||
| 17 | Peptide analog 53 | Drug Info | [1] | |||
| 18 | Peptide analog 54 | Drug Info | [1] | |||
| 19 | PMID26560530-Compound-1 | Drug Info | [1] | |||
| 20 | PMID26560530-Compound-11 | Drug Info | [1] | |||
| 21 | PMID26560530-Compound-12 | Drug Info | [1] | |||
| 22 | PMID26560530-Compound-13 | Drug Info | [1] | |||
| 23 | PMID26560530-Compound-14 | Drug Info | [1] | |||
| 24 | PMID26560530-Compound-15 | Drug Info | [1] | |||
| 25 | PMID26560530-Compound-16 | Drug Info | [1] | |||
| 26 | PMID26560530-Compound-17 | Drug Info | [1] | |||
| 27 | PMID26560530-Compound-18 | Drug Info | [1] | |||
| 28 | PMID26560530-Compound-2 | Drug Info | [1] | |||
| 29 | PMID26560530-Compound-23 | Drug Info | [1] | |||
| 30 | PMID26560530-Compound-24 | Drug Info | [1] | |||
| 31 | PMID26560530-Compound-25 | Drug Info | [1] | |||
| 32 | PMID26560530-Compound-26 | Drug Info | [1] | |||
| 33 | PMID26560530-Compound-27 | Drug Info | [1] | |||
| 34 | PMID26560530-Compound-3 | Drug Info | [1] | |||
| 35 | PMID26560530-Compound-31 | Drug Info | [1] | |||
| 36 | PMID26560530-Compound-32 | Drug Info | [1] | |||
| 37 | PMID26560530-Compound-33 | Drug Info | [1] | |||
| 38 | PMID26560530-Compound-34 | Drug Info | [1] | |||
| 39 | PMID26560530-Compound-35 | Drug Info | [1] | |||
| 40 | PMID26560530-Compound-4 | Drug Info | [1] | |||
| 41 | PMID26560530-Compound-46 | Drug Info | [1] | |||
| 42 | PMID26560530-Compound-47 | Drug Info | [1] | |||
| 43 | PMID26560530-Compound-48 | Drug Info | [1] | |||
| 44 | PMID26560530-Compound-49 | Drug Info | [1] | |||
| 45 | PMID26560530-Compound-5 | Drug Info | [1] | |||
| 46 | PMID26560530-Compound-50 | Drug Info | [1] | |||
| 47 | PMID26560530-Compound-54 | Drug Info | [1] | |||
| 48 | PMID26560530-Compound-6 | Drug Info | [1] | |||
| 49 | PMID26560530-Compound-7 | Drug Info | [1] | |||
| 50 | PMID26560530-Compound-8 | Drug Info | [1] | |||
| 51 | Pyrazolodiazepine derivative 1 | Drug Info | [1] | |||
| 52 | Sulfonamide derivative 9 | Drug Info | [1] | |||
| 53 | Triazole derivative 1 | Drug Info | [1] | |||
| 54 | NTU281 | Drug Info | [2] | |||
| 55 | Guanosine-5'-Diphosphate | Drug Info | [3] | |||
| 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: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of human transglutaminase 2 complex with adenosine 5' Triphosphate | PDB:3LY6 | ||||
| Method | X-ray diffraction | Resolution | 3.14 Å | Mutation | No | [4] |
| PDB Sequence |
ELVLERCDLE
13 LETNGRDHHT23 ADLCREKLVV33 RRGQPFWLTL43 HFEGRNYEAS53 VDSLTFSVVT 63 GPAPSQEAGT73 KARFPLRDAV83 GDWTATVVDQ95 QDCTLSLQLT105 TPANAPIGLY 115 RLSLEASTGY125 QGSSFVLGHF135 ILLFNAWCPA145 DAVYLDSEEE155 RQEYVLTQQG 165 FIYQGSAKFI175 KNIPWNFGQF185 EDGILDICLI195 LLDVNPKFLK205 NAGRDCSRRS 215 SPVYVGRVGS225 GMVNCNDDQG235 VLLGRWDNNY245 GDGVSPMSWI255 GSVDILRRWK 265 NHGCQRVKYG275 QCWVFAAVAC285 TVLRCLGIPT295 RVVTNYNSAH305 DQNSNLLIEY 315 FRNEFGEIQG325 DKSEMIWNFH335 CWVESWMTRP345 DLQPGYEGWQ355 ALDPTPQEKS 365 EGTYCCGPVP375 VRAIKEGDLS385 TKYDAPFVFA395 EVNADVVDWI405 QQDDGSVHKS 415 INRSLIVGLK425 ISTKSVGRDE435 REDITHTYKY445 PEGSSEEREA455 FTRANHLNKL 465 AEKEETGMAM475 RIRVGQSMNM485 GSDFDVFAHI495 TNNTAEEYVC505 RLLLCARTVS 515 YNGILGPECG525 TKYLLNLNLE535 PFSEKSVPLC545 ILYEKYRDCL555 TESNLIKVRA 565 LLVEPVINSY575 LLAERDLYLE585 NPEIKIRILG595 EPKQKRKLVA605 EVSLQNPLPV 615 ALEGCTFTVE625 GAGLTEEQKT635 VEIPDPVEAG645 EEVKVRMDLL655 PLHMGLHKLV 665 VNFESDKLKA675 VKGFRNVIIG685 PAL
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| Ligand Name: Guanosine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | HUMAN TISSUE TRANSGLUTAMINASE IN GDP BOUND FORM | PDB:1KV3 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [5] |
| PDB Sequence |
ETNGRDHHTA
24 DLCREKLVVR34 RGQPFWLTLS56 LTFSVVTGPA66 PSQEAGTKAR76 FPLRDAVEEG 86 DWTATVVDQQ96 DCTLSLQLTT106 PANAPIGLYR116 LSLEASGHFI136 LLFNAWCPAD 146 AVYLDSEEER156 QEYVLTQQGF166 IYQGSAKFIK176 NIPWNFGQFQ186 DGILDICLIL 196 LDVNPKFLKN206 AGRDCSRRSS216 PVYVGRVGSG226 MVNCNDDQGV236 LLGRWDNNYG 246 DGVSPMSWIG256 SVDILRRWKN266 HGCQRVKYGQ276 CWVFAAVACT286 VLRCLGIPTR 296 VVTNYNSAHD306 QNSNLLIEYF316 RNEFGEIQGD326 KSEMIWNFHC336 WVESWMTRPD 346 LQPGYEGWQA356 LDPTPQEKSE366 GTYCCGPVPV376 RAIKEGDLST386 KYDAPFVFAE 396 VNADVVDWIQ406 QDDGSVHKSI416 NRSLIVGLKI426 STKSVGRDER436 EDITHTYKYP 446 EGSSEEREAF456 TRANHLNKLA466 EKEETGMAMR476 IRVGQSMNMG486 SDFDVFAHIT 496 NNTAEEYVCR506 LLLCARTVSY516 NGILGPECGT526 KYLLNLTLEP536 FSEKSVPLCI 546 LYEKYRDCLT556 ESNLIKVRAL566 LVEPVINSYL576 LAERDLYLEN586 PEIKIRILGE 596 PKQKRKLVAE606 VSLQNPLPVA616 LEGCTFTVEG626 AGLTEEQKTV636 EIPDPVEAGE 646 EVKVRMDLVP656 LHMGLHKLVV666 NFESDKLKAV676 KGFRNVIIGP686 A |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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).
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
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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| Degree | 11 | Degree centrality | 1.18E-03 | Betweenness centrality | 6.38E-04 |
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| Closeness centrality | 2.26E-01 | Radiality | 1.40E+01 | Clustering coefficient | 3.64E-02 |
| Neighborhood connectivity | 2.46E+01 | Topological coefficient | 1.09E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Huntington's disease | |||||
| PID Pathway | [+] 3 PID Pathways | + | ||||
| 1 | Beta1 integrin cell surface interactions | |||||
| 2 | Thromboxane A2 receptor signaling | |||||
| 3 | Alpha9 beta1 integrin signaling events | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Transglutaminase inhibitors: a patent review.Expert Opin Ther Pat. 2016;26(1):49-63. | |||||
| REF 2 | Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855. | |||||
| REF 3 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 4 | Crystal structure of human transglutaminase 2 in complex with adenosine triphosphate. Int J Biol Macromol. 2010 Aug 1;47(2):190-5. | |||||
| REF 5 | Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2743-7. | |||||
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