Target Information
| Target General Information | Top | |||||
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| Target ID |
T21580
(Former ID: TTDI02476)
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| Target Name |
GTPase activating protein (RASA1)
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| Synonyms |
p120GAP; RasGAP; Ras p21 protein activator; Ras GTPase-activating protein 1; RASA; GTPase-activating protein; GAP
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| Gene Name |
RASA1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. Inhibitory regulator of the Ras-cyclic AMP pathway.
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| UniProt ID | ||||||
| Sequence |
MMAAEAGSEEGGPVTAGAGGGGAAAGSSAYPAVCRVKIPAALPVAAAPYPGLVETGVAGT
LGGGAALGSEFLGAGSVAGALGGAGLTGGGTAAGVAGAAAGVAGAAVAGPSGDMALTKLP TSLLAETLGPGGGFPPLPPPPYLPPLGAGLGTVDEGDSLDGPEYEEEEVAIPLTAPPTNQ WYHGKLDRTIAEERLRQAGKSGSYLIRESDRRPGSFVLSFLSQMNVVNHFRIIAMCGDYY IGGRRFSSLSDLIGYYSHVSCLLKGEKLLYPVAPPEPVEDRRRVRAILPYTKVPDTDEIS FLKGDMFIVHNELEDGWMWVTNLRTDEQGLIVEDLVEEVGREEDPHEGKIWFHGKISKQE AYNLLMTVGQVCSFLVRPSDNTPGDYSLYFRTNENIQRFKICPTPNNQFMMGGRYYNSIG DIIDHYRKEQIVEGYYLKEPVPMQDQEQVLNDTVDGKEIYNTIRRKTKDAFYKNIVKKGY LLKKGKGKRWKNLYFILEGSDAQLIYFESEKRATKPKGLIDLSVCSVYVVHDSLFGRPNC FQIVVQHFSEEHYIFYFAGETPEQAEDWMKGLQAFCNLRKSSPGTSNKRLRQVSSLVLHI EEAHKLPVKHFTNPYCNIYLNSVQVAKTHAREGQNPVWSEEFVFDDLPPDINRFEITLSN KTKKSKDPDILFMRCQLSRLQKGHATDEWFLLSSHIPLKGIEPGSLRVRARYSMEKIMPE EEYSEFKELILQKELHVVYALSHVCGQDRTLLASILLRIFLHEKLESLLLCTLNDREISM EDEATTLFRATTLASTLMEQYMKATATQFVHHALKDSILKIMESKQSCELSPSKLEKNED VNTNLTHLLNILSELVEKIFMASEILPPTLRYIYGCLQKSVQHKWPTNTTMRTRVVSGFV FLRLICPAILNPRMFNIISDSPSPIAARTLILVAKSVQNLANLVEFGAKEPYMEGVNPFI KSNKHRMIMFLDELGNVPELPDTTEHSRTDLSRDLAALHEICVAHSDELRTLSNERGAQQ HVLKKLLAITELLQQKQNQYTKTNDVR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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: Guanosine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | RAS-RASGAP COMPLEX | PDB:1WQ1 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
MPEEEYSEFK
727 ELILQKELHV737 VYALSHVCGQ747 DRTLLASILL757 RIFLHEKLES767 LLLCTLNDRE 777 ISMEDEATTL787 FRATTLASTL797 MEQYMKATAT807 QFVHHALKDS817 ILKIMESKQS 827 CELSPSKLEK837 NEDVNTNLTH847 LLNILSELVE857 KIFMASEILP867 PTLRYIYGCL 877 QKSVQHKWPT887 NTTMRTRVVS897 GFVFLRLICP907 AILNPRMFNI917 ISDSPSPIAA 927 RTLILVAKSV937 QNLANLVEFG947 AKEPYMEGVN957 PFIKSNKHRM967 IMFLDELGNV 977 PELPDTTEHS987 RTDLSRDLAA997 LHEICVAHSD1007 ELRTLSNERG1017 AQQHVLKKLL 1027 AITELLQQKQ1037
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| Ligand Name: Aluminum fluoride | Ligand Info | |||||
| Structure Description | RAS-RASGAP COMPLEX | PDB:1WQ1 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
MPEEEYSEFK
727 ELILQKELHV737 VYALSHVCGQ747 DRTLLASILL757 RIFLHEKLES767 LLLCTLNDRE 777 ISMEDEATTL787 FRATTLASTL797 MEQYMKATAT807 QFVHHALKDS817 ILKIMESKQS 827 CELSPSKLEK837 NEDVNTNLTH847 LLNILSELVE857 KIFMASEILP867 PTLRYIYGCL 877 QKSVQHKWPT887 NTTMRTRVVS897 GFVFLRLICP907 AILNPRMFNI917 ISDSPSPIAA 927 RTLILVAKSV937 QNLANLVEFG947 AKEPYMEGVN957 PFIKSNKHRM967 IMFLDELGNV 977 PELPDTTEHS987 RTDLSRDLAA997 LHEICVAHSD1007 ELRTLSNERG1017 AQQHVLKKLL 1027 AITELLQQKQ1037
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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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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| LIM and SH3 domain protein 1 (LASP1) | 36.207 (21/58) | 9.36E-06 | |
| Nebulette (NEBL) | 35.593 (21/59) | 2.00E-03 |
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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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| MAPK signaling pathway | hsa04010 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Ras signaling pathway | hsa04014 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Axon guidance | hsa04360 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Degree | 20 | Degree centrality | 2.15E-03 | Betweenness centrality | 6.25E-04 |
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| Closeness centrality | 2.43E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.53E-01 |
| Neighborhood connectivity | 5.88E+01 | Topological coefficient | 9.24E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases. Mol Cell Neurosci. 2017 Apr;80:18-31. | |||||
| REF 2 | The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 1997 Jul 18;277(5324):333-8. | |||||
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