Target Information
| Target General Information | Top | |||||
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| Target ID |
T55094
(Former ID: TTDR01256)
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| Target Name |
Acid-sensing ion channel 1 (ASIC1)
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| Synonyms |
Brain sodium channel 2; BNaC2; Amiloride-sensitive cation channel 2, neuronal; ASIC1; ACCN2
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| Gene Name |
ASIC1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| Function |
Isoform 1 does not display proton-gated cation channel activity.
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| BioChemical Class |
Amiloride-sensitive sodium channel
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| UniProt ID | ||||||
| Sequence |
MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCV
CTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNN RYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCS AEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETS FEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLD FFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEY CVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETI EQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSA DKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T42DE3 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Amiloride | Drug Info | Approved | Congestive heart failure | [2], [3] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | PPC-5650 | Drug Info | Phase 1 | Pain | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Amiloride | Drug Info | [1] | |||
| 2 | PPC-5650 | Drug Info | [4] | |||
| Blocker | [+] 1 Blocker drugs | + | ||||
| 1 | PcTx1 | Drug Info | [5], [6] | |||
| 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-(Acetylamino)-2-Deoxy-a-D-Glucopyranose | Ligand Info | |||||
| Structure Description | hASIC1a co-crystallized with Nafamostat | PDB:6L6N | ||||
| Method | X-ray diffraction | Resolution | 2.86 Å | Mutation | No | [7] |
| PDB Sequence |
LWALCFLGSL
54 AVLLCVCTER64 VQYYFHYHHV74 TKLDEVAASQ84 LTFPAVTLCN94 LNEFRFSQVS 104 KNDLYHAGEL114 LALLNNRYEI124 PDTQMADEKQ134 LEILQDKANF144 RSFKPKPFNM 154 REFYDRAGHD164 IRDMLLSCHF174 RGEVCSAEDF184 KVVFTRYGKC194 YTFNSGRDGR 204 PRLKTMKGGT214 GNGLEIMLDI224 QQDEYLPVWG234 ETDETSFEAG244 IKVQIHSQDE 254 PPFIDQLGFG264 VAPGFQTFVA274 CQEQRLIYLP284 PPWGTCKAVT294 MDSDLDFFDS 304 YSITACRIDC314 ETRYLVENCN324 CRMVHMPGDA334 PYCTPEQYKE344 CADPALDFLV 354 EKDQEYCVCE364 MPCNLTRYGK374 ELSMVKIPSK384 ASAKYLAKKF394 NKSEQYIGEN 404 ILVLDIFFEV414 LNYETIEQKK424 AYEIAGLLGD434 IGGQMGLFIG444 ASILT |
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| Ligand Name: Cholesterol hemisuccinate | Ligand Info | |||||
| Structure Description | Cryo-EM strucutre of human acid-sensing ion channel 1a at pH 8.0 | PDB:7CFS | ||||
| Method | Electron microscopy | Resolution | 3.56 Å | Mutation | No | [8] |
| PDB Sequence |
SLKRALWALC
49 FLGSLAVLLC59 VCTERVQYYF69 HYHHVTKLDE79 VAASQLTFPA89 VTLCNLNEFR 99 FSQVSKNDLY109 HAGELLALLN119 NRYEIPDTQM129 ADEKQLEILQ139 DKANFRSFKP 149 KPFNMREFYD159 RAGHDIRDML169 LSCHFRGEVC179 SAEDFKVVFT189 RYGKCYTFNS 199 GRDGRPRLKT209 MKGGTGNGLE219 IMLDIQQDEY229 LPVWGETDET239 SFEAGIKVQI 249 HSQDEPPFID259 QLGFGVAPGF269 QTFVACQEQR279 LIYLPPPWGT289 CKAVTMDSDL 299 DFFDSYSITA309 CRIDCETRYL319 VENCNCRMVH329 MPGDAPYCTP339 EQYKECADPA 349 LDFLVEKDQE359 YCVCEMPCNL369 TRYGKELSMV379 KIPSKASAKY389 LAKKFNKSEQ 399 YIGENILVLD409 IFFEVLNYET419 IEQKKAYEIA429 GLLGDIGGQM439 GLFIGASILT 449 VLELFDYAYE459 VIKHKL
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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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| Inflammatory mediator regulation of TRP channels | hsa04750 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.71E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.10E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Inflammatory mediator regulation of TRP channels | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Stimuli-sensing channels | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Iron uptake and transport | |||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2421). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 070346. | |||||
| REF 4 | ClinicalTrials.gov (NCT01449487) Investigation of Efficacy and Safety of PPC-5650 to Experimental Induced Sensation and Pain in the Rectosigmoid. U.S. National Institutes of Health. | |||||
| REF 5 | Challenges in analgesic drug development. Clin Pharmacol Ther. 2009 Oct;86(4):447-50. | |||||
| REF 6 | Peptides inhibitors of acid-sensing ion channels. Toxicon. 2007 Feb;49(2):271-84. | |||||
| REF 7 | hASIC1a co-crystallized with Mamb-1 | |||||
| REF 8 | Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1. Elife. 2020 Sep 11;9:e57096. | |||||
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