Target Information
Target General Information | Top | |||||
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Target ID |
T49522
(Former ID: TTDR00108)
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Target Name |
Pleiotrophin (PTN)
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Synonyms |
Osteoblast-specific factor 1; Osteoblast specific factor 1; OSF-1; NEGF1; Heparin-binding neurite outgrowth-promoting factor 1; Heparin-binding neurite outgrowth-promoting factor; Heparin-binding neurite outgrowth promoting factor 1; Heparin-binding growth-associated molecule; Heparin-binding brain mitogen; HBNF1; HBNF-1; HBNF; HBBM; HB-GAM
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Gene Name |
PTN
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups. Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone. Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation. Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-AKT pathway. Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway. Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-773' phosphorylation. In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway. Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion. Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition. Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation. Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway. Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration. In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway. Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors.
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UniProt ID | ||||||
Sequence |
MQAQQYQQQRRKFAAAFLAFIFILAAVDTAEAGKKEKPEKKVKKSDCGEWQWSVCVPTSG
DCGLGTREGTRTGAECKQTMKTQRCKIPCNWKKQFGAECKYQFQAWGECDLNTALKTRTG SLKRALHNAECQKTVTISKPCGKLTKPKPQAESKKKKKEGKKQEKMLD Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T41DXP |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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 | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 8.80E-06 |
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Closeness centrality | 1.93E-01 | Radiality | 1.33E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 7.00E+00 | Topological coefficient | 2.61E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs |
References | Top | |||||
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REF 1 | New paradigms for the treatment of cancer: the role of anti-angiogenesis agents. Adv Cancer Res. 2000;79:1-38. |
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