Target Information
| Target General Information | Top | |||||
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| Target ID |
T22945
(Former ID: TTDI01517)
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| Target Name |
Antigen peptide transporter 1 (TAP1)
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| Synonyms |
Y3; Really interesting new gene 4 protein; RING4; Peptide transporter involved in antigen processing 1; Peptide transporter TAP1; Peptide transporter PSF1; Peptide supply factor 1; PSF1; PSF-1; ATP-binding cassette sub-family B member 2; ABCB2
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| Gene Name |
TAP1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules.
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| UniProt ID | ||||||
| Sequence |
MAELLASAGSACSWDFPRAPPSFPPPAASRGGLGGTRSFRPHRGAESPRPGRDRDGVRVP
MASSRCPAPRGCRCLPGASLAWLGTVLLLLADWVLLRTALPRIFSLLVPTALPLLRVWAV GLSRWAVLWLGACGVLRATVGSKSENAGAQGWLAALKPLAAALGLALPGLALFRELISWG APGSADSTRLLHWGSHPTAFVVSYAAALPAAALWHKLGSLWVPGGQGGSGNPVRRLLGCL GSETRRLSLFLVLVVLSSLGEMAIPFFTGRLTDWILQDGSADTFTRNLTLMSILTIASAV LEFVGDGIYNNTMGHVHSHLQGEVFGAVLRQETEFFQQNQTGNIMSRVTEDTSTLSDSLS ENLSLFLWYLVRGLCLLGIMLWGSVSLTMVTLITLPLLFLLPKKVGKWYQLLEVQVRESL AKSSQVAIEALSAMPTVRSFANEEGEAQKFREKLQEIKTLNQKEAVAYAVNSWTTSISGM LLKVGILYIGGQLVTSGAVSSGNLVTFVLYQMQFTQAVEVLLSIYPRVQKAVGSSEKIFE YLDRTPRCPPSGLLTPLHLEGLVQFQDVSFAYPNRPDVLVLQGLTFTLRPGEVTALVGPN GSGKSTVAALLQNLYQPTGGQLLLDGKPLPQYEHRYLHRQVAAVGQEPQVFGRSLQENIA YGLTQKPTMEEITAAAVKSGAHSFISGLPQGYDTEVDEAGSQLSGGQRQAVALARALIRK PCVLILDDATSALDANSQLQVEQLLYESPERYSRSVLLITQHLSLVEQADHILFLEGGAI REGGTHQQLMEKKGCYWAMVQAPADAPE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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 diphosphate | Ligand Info | |||||
| Structure Description | Crystal Structure of the C-terminal ATPase domain of human TAP1 | PDB:1JJ7 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
GLLTPLHLEG
501 LVQFQDVSFA511 YPNRPDVLVL521 QGLTFTLRPG531 EVTALVGPNG541 SGKSTVAALL 551 QNLYQPTGGQ561 LLLDGKPLPQ571 YEHRYLHRQV581 AAVGQEPQVF591 GRSLQENIAY 601 GLTQKPTMEE611 ITAAAVKSGA621 HSFISGLPQG631 YDTEVDEAGS641 QLSGGQRQAV 651 ALARALIRKP661 CVLILDDATS671 ALDANSQLQV681 EQLLYESPER691 YSRSVLLITQ 701 HLSLVEQADH711 ILFLEGGAIR721 EGGTHQQLME731 KKGCYWAMVQ741 A |
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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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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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| ABC transporters | hsa02010 | Affiliated Target |
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| Class: Environmental Information Processing => Membrane transport | Pathway Hierarchy | ||
| Phagosome | hsa04145 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Antigen processing and presentation | hsa04612 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 8.14E-05 |
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| Closeness centrality | 1.94E-01 | Radiality | 1.33E+01 | Clustering coefficient | 5.00E-01 |
| Neighborhood connectivity | 2.40E+01 | Topological coefficient | 2.22E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | A novel mutation in TAP1 gene leading to MHC class I deficiency: Report of two cases and review of the literature. Clin Immunol. 2017 May;178:74-78. | |||||
| REF 2 | Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing. EMBO J. 2001 Sep 3;20(17):4964-72. | |||||
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