Target Information
| Target General Information | Top | |||||
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| Target ID |
T52133
(Former ID: TTDI02424)
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| Target Name |
Aspartate beta-hydroxylase (ASPH)
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| Synonyms |
Peptideaspartate betadioxygenase; Aspartyl/asparaginyl betahydroxylase; ASPH; ASP betahydroxylase
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| Gene Name |
ASPH
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells. {ECO:0000269|PubMed:22586105}.
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| BioChemical Class |
Paired donor oxygen oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.14.11.16
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| Sequence |
MAQRKNAKSSGNSSSSGSGSGSTSAGSSSPGARRETKHGGHKNGRKGGLSGTSFFTWFMV
IALLGVWTSVAVVWFDLVDYEEVLGKLGIYDADGDGDFDVDDAKVLLGLKERSTSEPAVP PEEAEPHTEPEEQVPVEAEPQNIEDEAKEQIQSLLHEMVHAEHVEGEDLQQEDGPTGEPQ QEDDEFLMATDVDDRFETLEPEVSHEETEHSYHVEETVSQDCNQDMEEMMSEQENPDSSE PVVEDERLHHDTDDVTYQVYEEQAVYEPLENEGIEITEVTAPPEDNPVEDSQVIVEEVSI FPVEEQQEVPPETNRKTDDPEQKAKVKKKKPKLLNKFDKTIKAELDAAEKLRKRGKIEEA VNAFKELVRKYPQSPRARYGKAQCEDDLAEKRRSNEVLRGAIETYQEVASLPDVPADLLK LSLKRRSDRQQFLGHMRGSLLTLQRLVQLFPNDTSLKNDLGVGYLLIGDNDNAKKVYEEV LSVTPNDGFAKVHYGFILKAQNKIAESIPYLKEGIESGDPGTDDGRFYFHLGDAMQRVGN KEAYKWYELGHKRGHFASVWQRSLYNVNGLKAQPWWTPKETGYTELVKSLERNWKLIRDE GLAVMDKAKGLFLPEDENLREKGDWSQFTLWQQGRRNENACKGAPKTCTLLEKFPETTGC RRGQIKYSIMHPGTHVWPHTGPTNCRLRMHLGLVIPKEGCKIRCANETKTWEEGKVLIFD DSFEHEVWQDASSFRLIFIVDVWHPELTPQQRRSLPAI 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: 2-(carboxymethylamino)-2-oxoacetic acid | Ligand Info | |||||
| Structure Description | Aspartyl/Asparaginyl beta-hydroxylase (AspH) H679A in complex with Mn, NOG and Factor X peptide fragment (39mer-4Ser) | PDB:6Q9F | ||||
| Method | X-ray diffraction | Resolution | 1.63 Å | Mutation | Yes | [2] |
| PDB Sequence |
KPKLLNKFDK
339 TIKAELDAAE349 KLRKRGKIEE359 AVNAFKELVR369 KYPQSPRARY379 GKAQCEDDLA 389 EKRRSNEVLR399 GAIETYQEVA409 SLPDVPADLL419 KLSLKRRSDR429 QQFLGHMRGS 439 LLTLQRLVQL449 FPNDTSLKND459 LGVGYLLIGD469 NDNAKKVYEE479 VLSVTPNDGF 489 AKVHYGFILK499 AQNKIAESIP509 YLKEGIESGD519 PGTDDGRFYF529 HLGDAMQRVG 539 NKEAYKWYEL549 GHKRGHFASV559 WQRSLYNVNG569 LKAQPWWTPK579 ETGYTELVKS 589 LERNWKLIRD599 EGLAVMDKAK609 GLFLPEDENL619 REKGDWSQFT629 LWQQGRRNEN 639 ACKGAPKTCT649 LLEKFPETTG659 CRRGQIKYSI669 MHPGTHVWPA679 TGPTNCRLRM 689 HLGLVIPKEG699 CKIRCANETK709 TWEEGKVLIF719 DDSFEHEVWQ729 DASSFRLIFI 739 VDVWHPELTP749 QQRRSLPAI
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Propanoic acid | Ligand Info | |||||
| Structure Description | Aspartyl/Asparaginyl beta-hydroxylase (AspH) H725A in complex with Factor X peptide fragment (39mer-4Ser) | PDB:7E6J | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [3] |
| PDB Sequence |
KPKLLNKFDK
339 TIKAELDAAE349 KLRKRGKIEE359 AVNAFKELVR369 KYPQSPRARY379 GKAQCEDDLA 389 EKRRSNEVLR399 GAIETYQEVA409 SLPDVPADLL419 KLSLKRRSDR429 QQFLGHMRGS 439 LLTLQRLVQL449 FPNDTSLKND459 LGVGYLLIGD469 NDNAKKVYEE479 VLSVTPNDGF 489 AKVHYGFILK499 AQNKIAESIP509 YLKEGIESGD519 PGTDDGRFYF529 HLGDAMQRVG 539 NKEAYKWYEL549 GHKRGHFASV559 WQRSLYNVNG569 LKAQPWWTPK579 ETGYTELVKS 589 LERNWKLIRD599 EGLAVMDKAK609 GLFLPEDENL619 REKGDWSQFT629 LWQQGRRNEN 639 ACKGAPKTCT649 LLEKFPETTG659 CRRGQIKYSI669 MHPGTHVWPH679 TGPTNCRLRM 689 HLGLVIPKEG699 CKIRCANETK709 TWEEGKVLIF719 DDSFEAEVWQ729 DASSFRLIFI 739 VDVWHPELTP749 QQRRSLPAI
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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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| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cardiac muscle contraction | hsa04260 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 1.02E-04 |
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| Closeness centrality | 1.70E-01 | Radiality | 1.27E+01 | Clustering coefficient | 6.00E-01 |
| Neighborhood connectivity | 7.60E+00 | Topological coefficient | 3.45E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Aspartate beta-hydroxylase promotes cholangiocarcinoma progression by modulating RB1 phosphorylation. Cancer Lett. 2018 Aug 10;429:1-10. | |||||
| REF 2 | Aspartyl/Asparaginyl beta-hydroxylase (AspH) H679A in complex with Mn, NOG and Factor X peptide fragment (39mer-4Ser) | |||||
| REF 3 | Human Oxygenase Variants Employing a Single Protein Fe(II) Ligand Are Catalytically Active. Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14657-14663. | |||||
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