Target Information
Target General Information | Top | |||||
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Target ID |
T80395
(Former ID: TTDI00045)
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Target Name |
GAP-associated tyrosine phosphoprotein p62 (KHDRBS1)
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Synonyms |
p68; p21 Ras GTPaseactivating proteinassociated p62; p21 Ras GTPase-activating protein-associated p62; Srcassociated in mitosis 68 kDa protein; Src-associated in mitosis 68 kDa protein; Sam68; KH domaincontaining, RNAbinding, signal transductionassociated protein 1; KH domain-containing, RNA-binding, signal transduction-associated protein 1; GAPassociated tyrosine phosphoprotein p62
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Gene Name |
KHDRBS1
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to. RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner. In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1. Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4. Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors.
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UniProt ID | ||||||
Sequence |
MQRRDDPAARMSRSSGRSGSMDPSGAHPSVRQTPSRQPPLPHRSRGGGGGSRGGARASPA
TQPPPLLPPSATGPDATVGGPAPTPLLPPSATASVKMEPENKYLPELMAEKDSLDPSFTH AMQLLTAEIEKIQKGDSKKDDEENYLDLFSHKNMKLKERVLIPVKQYPKFNFVGKILGPQ GNTIKRLQEETGAKISVLGKGSMRDKAKEEELRKGGDPKYAHLNMDLHVFIEVFGPPCEA YALMAHAMEEVKKFLVPDMMDDICQEQFLELSYLNGVPEPSRGRGVPVRGRGAAPPPPPV PRGRGVGPPRGALVRGTPVRGAITRGATVTRGVPPPPTVRGAPAPRARTAGIQRIPLPPP PAPETYEEYGYDDTYAEQSYEGYEGYYSQSQGDSEYYDYGHGEVQDSYEAYGQDDWNGTR PSLKAPPARPVKGAYREHPYGRY 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 |
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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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 | 15 | Degree centrality | 1.61E-03 | Betweenness centrality | 1.37E-03 |
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Closeness centrality | 2.38E-01 | Radiality | 1.42E+01 | Clustering coefficient | 1.52E-01 |
Neighborhood connectivity | 4.84E+01 | Topological coefficient | 1.13E-01 | 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 | Clinical significance and effect of Sam68 expression in gastric cancer. Oncol Lett. 2018 Apr;15(4):4745-4752. |
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