Target Information
| Target General Information | Top | |||||
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| Target ID |
T78581
(Former ID: TTDR00184)
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| Target Name |
Galanin receptor type 1 (GAL1-R)
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| Synonyms |
GALR1; GALR-1; GALNR1; GALN1R; GAL1-R
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| Gene Name |
GALR1
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| Function |
The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Receptor for the hormone galanin. G protein-coupled peptide receptor activity. Neuropeptide binding. Peptide hormone binding.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MELAVGNLSEGNASWPEPPAPEPGPLFGIGVENFVTLVVFGLIFALGVLGNSLVITVLAR
SKPGKPRSTTNLFILNLSIADLAYLLFCIPFQATVYALPTWVLGAFICKFIHYFFTVSML VSIFTLAAMSVDRYVAIVHSRRSSSLRVSRNALLGVGCIWALSIAMASPVAYHQGLFHPR ASNQTFCWEQWPDPRHKKAYVVCTFVFGYLLPLLLICFCYAKVLNHLHKKLKNMSKKSEA SKKKTAQTVLVVVVVFGISWLPHHIIHLWAEFGVFPLTPASFLFRITAHCLAYSNSSVNP IIYAFLSENFRKAYKQVFKCHIRKDSHLSDTKESKSRIDTPPSTNCTHV 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: Cholesterol | Ligand Info | |||||
| Structure Description | Galanin-bound galanin receptor 1 in complex with Gi | PDB:7WQ3 | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | Yes | [7] |
| PDB Sequence |
ENFVTLVVFG
41 LIFALGVLGN51 SLVITVLARS61 KPGKPRSTTN71 LFILNLSIAD81 LAYLLFCIPF 91 QATVYALPTW101 VLGAFICKFI111 HYFFTVSMLV121 SIFTLAAMSV131 DRYVAIVHSR 141 RSSSLRVSRN151 ALLGVGCIWA161 LSIAMASPVA171 YHQGLFHPRA181 SNQTFCWEQW 191 PDPRHKKAYV201 VCTFVFGYLL211 PLLLICFCYA221 KVLNHLHKKL231 KNMSKKSEAS 241 KKKTAQTVLV251 VVVVFGISWL261 PHHIIHLWAE271 FGVFPLTPAS281 FLFRITAHCL 291 AYSNSSVNPI301 IYAFLSENFR311 KAYKQVFKC
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PHE73
4.424
ALA105
4.551
PHE106
3.601
LYS109
4.177
PHE110
3.593
TYR113
4.337
PHE124
3.976
ALA127
3.735
ALA128
3.753
VAL131
3.723
ASP132
4.430
LEU146
3.973
ARG147
3.361
VAL148
4.644
ASN151
3.298
GLY155
4.052
ILE159
3.859
ILE164
3.732
SER168
4.143
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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 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 Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.36E-01 | Radiality | 1.14E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 4.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Peptide GPCRs | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43. | |||||
| REF 2 | Structural requirements for a lipoamino acid in modulating the anticonvulsant activities of systemically active galanin analogues. J Med Chem. 2009 Mar 12;52(5):1310-6. | |||||
| REF 3 | Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic de... J Med Chem. 2010 Feb 25;53(4):1871-5. | |||||
| REF 4 | cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8. | |||||
| REF 5 | Anticonvulsant activity of a nonpeptide galanin receptor agonist. Proc Natl Acad Sci U S A. 2002 May 14;99(10):7136-41. | |||||
| REF 6 | Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities. J Med Chem. 2008 Dec 25;51(24):8038-47. | |||||
| REF 7 | Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors. doi:10.1038/s41467-022-29072-3. | |||||
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