Target Information
| Target General Information | Top | |||||
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| Target ID |
T32780
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| Target Name |
Asialoglycoprotein receptor 1 (ASGR1)
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| Synonyms |
Hepatic lectin H1; HL-1; C-type lectin domain family 4 member H1
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| Gene Name |
ASGR1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Cardiovascular disease [ICD-11: BA00-BE2Z] | |||||
| Function |
Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.
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| UniProt ID | ||||||
| Sequence |
MTKEYQDLQHLDNEESDHHQLRKGPPPPQPLLQRLCSGPRLLLLSLGLSLLLLVVVCVIG
SQNSQLQEELRGLRETFSNFTASTEAQVKGLSTQGGNVGRKMKSLESQLEKQQKDLSEDH SSLLLHVKQFVSDLRSLSCQMAALQGNGSERTCCPVNWVEHERSCYWFSRSGKAWADADN YCRLEDAHLVVVTSWEEQKFVQHHIGPVNTWMGLHDQNGPWKWVDGTDYETGFKNWRPEQ PDDWYGHGLGGGEDCAHFTDDGRWNDDVCQRPYRWVCETELDKASQEPPLL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T37SKN | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | AMG 529 | Drug Info | Phase 1 | Cardiovascular disease | [1] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | AMG 529 | Drug Info | [1] | |||
| 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: N-[(1s,2r,3r,4r,5s)-2,3-Dihydroxy-1-(Hydroxymethyl)-6,8-Dioxabicyclo[3.2.1]octan-4-Yl]acetamide | Ligand Info | |||||
| Structure Description | Efficient targeting of the asialoglycoprotein receptor by polyvalent display of a compact galactosamine mimic | PDB:5JQ1 | ||||
| Method | X-ray diffraction | Resolution | 1.83 Å | Mutation | No | [2] |
| PDB Sequence |
TCCPVNWVEH
160 ERSCYWFSRS170 GKAWADADNY180 CRLEDAHLVV190 VTSWEEQKFV200 QHHIGPVNTW 210 MGLHDQNGPW220 KWVDGTDYET230 GFKNWRPEQP240 DDWYGHGLGG250 GEDCAHFTDD 260 GRWNDDVCQR270 PYRWVCETEL280
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| Ligand Name: 5-[(2~{R},3~{R},4~{R},5~{R},6~{R})-3-acetamido-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-2-yl]oxy-~{N}-[3-(propanoylamino)propyl]pentanamide | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF ASGPR 1 IN COMPLEX WITH GN-A. | PDB:6YAU | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | No | [3] |
| PDB Sequence |
CCPVNWVEHE
161 RSCYWFSRSG171 KAWADADNYC181 RLEDAHLVVV191 TSWEEQKFVQ201 HHIGPVNTWM 211 GLHDQNGPWK221 WVDGTDYETG231 FKNWRPEQPD241 DWYGHGLGGG251 EDCAHFTDDG 261 RWNDDVCQRP271 YRWVCETEL
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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).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Putative C-type lectin-like domain family 1 (CLECL1P) | 25.862 (15/58) | 5.00E-03 | |
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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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| Thyroid hormone synthesis | hsa04918 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Thyroid hormone synthesis | |||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | Efficient Liver Targeting by Polyvalent Display of a Compact Ligand for the Asialoglycoprotein Receptor. J Am Chem Soc. 2017 Mar 8;139(9):3528-3536. | |||||
| REF 3 | Triantennary GalNAc Molecular Imaging Probes for Monitoring Hepatocyte Function in a Rat Model of Nonalcoholic Steatohepatitis. Adv Sci (Weinh). 2020 Nov 9;7(24):2002997. | |||||
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