Target Information
Target General Information | Top | |||||
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Target ID |
T58679
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Target Name |
Polyadenylate-binding protein 1 (PABPC1)
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Synonyms |
PABP-1; Poly(A)-binding protein 1
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Gene Name |
PABPC1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability.
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UniProt ID | ||||||
Sequence |
MNPSAPSYPMASLYVGDLHPDVTEAMLYEKFSPAGPILSIRVCRDMITRRSLGYAYVNFQ
QPADAERALDTMNFDVIKGKPVRIMWSQRDPSLRKSGVGNIFIKNLDKSIDNKALYDTFS AFGNILSCKVVCDENGSKGYGFVHFETQEAAERAIEKMNGMLLNDRKVFVGRFKSRKERE AELGARAKEFTNVYIKNFGEDMDDERLKDLFGKFGPALSVKVMTDESGKSKGFGFVSFER HEDAQKAVDEMNGKELNGKQIYVGRAQKKVERQTELKRKFEQMKQDRITRYQGVNLYVKN LDDGIDDERLRKEFSPFGTITSAKVMMEGGRSKGFGFVCFSSPEEATKAVTEMNGRIVAT KPLYVALAQRKEERQAHLTNQYMQRMASVRAVPNPVINPYQPAPPSGYFMAAIPQTQNRA AYYPPSQIAQLRPSPRWTAQGARPHPFQNMPGAIRPAAPRPPFSTMRPASSQVPRVMSTQ RVANTSTQTMGPRPAAAAAAATPAVRTVPQYKYAAGVRNPQQHLNAQPQVTMQQPAVHVQ GQEPLTASMLASAPPQEQKQMLGERLFPLIQAMHPTLAGKITGMLLEIDNSELLHMLESP ESLRSKVDEAVAVLQAHQAKEAAQKAVNSATGVPTV Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ATRC-101 | Drug Info | Phase 1 | Solid tumour/cancer | [2] |
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 monophosphate | Ligand Info | |||||
Structure Description | X-RAY CRYSTAL STRUCTURE OF THE POLY(A)-BINDING PROTEIN IN COMPLEX WITH POLYADENYLATE RNA | PDB:1CVJ | ||||
Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
PDB Sequence |
ASLYVGDLHP
20 DVTEAMLYEK30 FSPAGPILSI40 RVCRDMITRR50 SLGYAYVNFQ60 QPADAERALD 70 TMNFDVIKGK80 PVRIMWSQRD90 PSLRKSGVGN100 IFIKNLDKSI110 DNKALYDTFS 120 AFGNILSCKV130 VCDENGSKGY140 GFVHFETQEA150 AERAIEKMNG160 MLLNDRKVFV 170 GRFKSRKER
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Ligand Name: Tilarginine | Ligand Info | |||||
Structure Description | Crystal structure of CARM1, sinefungin, and PABP1 peptide (R455) | PDB:5DX1 | ||||
Method | X-ray diffraction | Resolution | 1.93 Å | Mutation | Yes | [4] |
PDB Sequence |
GAIRPAAP
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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).
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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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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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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mRNA surveillance pathway | hsa03015 | Affiliated Target |
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Class: Genetic Information Processing => Translation | Pathway Hierarchy | ||
RNA degradation | hsa03018 | Affiliated Target |
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Class: Genetic Information Processing => Folding, sorting and degradation | Pathway Hierarchy |
Degree | 37 | Degree centrality | 3.98E-03 | Betweenness centrality | 3.84E-03 |
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Closeness centrality | 2.22E-01 | Radiality | 1.39E+01 | Clustering coefficient | 9.91E-02 |
Neighborhood connectivity | 1.51E+01 | Topological coefficient | 5.33E-02 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
References | Top | |||||
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REF 1 | Clinical pipeline report, company report or official report of Atreca. | |||||
REF 2 | ClinicalTrials.gov (NCT04244552) A Dose Escalation Trial of ATRC-101 in Adults With Advanced Solid Malignancies. U.S. National Institutes of Health. | |||||
REF 3 | Recognition of polyadenylate RNA by the poly(A)-binding protein. Cell. 1999 Sep 17;98(6):835-45. | |||||
REF 4 | Structural Insights into Ternary Complex Formation of Human CARM1 with Various Substrates. ACS Chem Biol. 2016 Mar 18;11(3):763-71. |
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