Target Information
Target General Information | Top | |||||
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Target ID |
T06475
(Former ID: TTDR00575)
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Target Name |
Nucleolin (NCL)
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Synonyms |
Protein C23
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Gene Name |
NCL
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Leukaemia [ICD-11: 2A60-2B33] | |||||
2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Nucleolin is the major nucleolar protein of growing eukaryotic cells.
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UniProt ID | ||||||
Sequence |
MVKLAKAGKNQGDPKKMAPPPKEVEEDSEDEEMSEDEEDDSSGEEVVIPQKKGKKAAATS
AKKVVVSPTKKVAVATPAKKAAVTPGKKAAATPAKKTVTPAKAVTTPGKKGATPGKALVA TPGKKGAAIPAKGAKNGKNAKKEDSDEEEDDDSEEDEEDDEDEDEDEDEIEPAAMKAAAA APASEDEDDEDDEDDEDDDDDEEDDSEEEAMETTPAKGKKAAKVVPVKAKNVAEDEDEEE DDEDEDDDDDEDDEDDDDEDDEEEEEEEEEEPVKEAPGKRKKEMAKQKAAPEAKKQKVEG TEPTTAFNLFVGNLNFNKSAPELKTGISDVFAKNDLAVVDVRIGMTRKFGYVDFESAEDL EKALELTGLKVFGNEIKLEKPKGKDSKKERDARTLLAKNLPYKVTQDELKEVFEDAAEIR LVSKDGKSKGIAYIEFKTEADAEKTFEEKQGTEIDGRSISLYYTGEKGQNQDYRGGKNST WSGESKTLVLSNLSYSATEETLQEVFEKATFIKVPQNQNGKSKGYAFIEFASFEDAKEAL NSCNKREIEGRAIRLELQGPRGSPNARSQPSKTLFVKGLSEDTTEETLKESFDGSVRARI VTDRETGSSKGFGFVDFNSEEDAKAAKEAMEDGEIDGNKVTLDWAKPKGEGGFGGRGGGR GGFGGRGGGRGGRGGFGGRGRGGFGGRGGFRGGRGGGGDHKPQGKKTKFE Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T41A2B |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | ACT-GRO-777 | Drug Info | Phase 2 | Solid tumour/cancer | [2] | |
2 | Itarnafloxin | Drug Info | Phase 2 | leukaemia | [1] | |
3 | IPP-204106 | Drug Info | Phase 1/2 | Solid tumour/cancer | [3] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | Itarnafloxin | Drug Info | [1] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | IPP-204106 | Drug Info | [5] |
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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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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Midasin (MDN1) | 23.596 (21/89) | 4.00E-03 |
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 | 21 | Degree centrality | 2.26E-03 | Betweenness centrality | 2.74E-03 |
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Closeness centrality | 2.57E-01 | Radiality | 1.45E+01 | Clustering coefficient | 1.62E-01 |
Neighborhood connectivity | 7.46E+01 | Topological coefficient | 8.55E-02 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | TCR Signaling Pathway | |||||
2 | IL2 Signaling Pathway | |||||
PID Pathway | [+] 4 PID Pathways | + | ||||
1 | Aurora B signaling | |||||
2 | Validated targets of C-MYC transcriptional activation | |||||
3 | Regulation of Telomerase | |||||
4 | Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | |||||
WikiPathways | [+] 5 WikiPathways | + | ||||
1 | Pathogenic Escherichia coli infection | |||||
2 | miR-targeted genes in squamous cell - TarBase | |||||
3 | miR-targeted genes in muscle cell - TarBase | |||||
4 | miR-targeted genes in lymphocytes - TarBase | |||||
5 | miR-targeted genes in epithelium - TarBase |
References | Top | |||||
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REF 1 | Targeting G-quadruplexes in gene promoters: a novel anticancer strategy . Nat Rev Drug Discov. 2011 April; 10(4): 261-275. | |||||
REF 2 | ClinicalTrials.gov (NCT00740441) A Phase II Study of AS1411 in Renal Cell Carcinoma. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT01711398) Dose-finding Adaptive Phase I/IIa Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IPP-204106N on Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 4 | Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma. J Cancer Ther. 2013 June 1; 4(4): 872-890. | |||||
REF 5 | Company report (ImmuPharma) |
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