Target Information
| Target General Information | Top | |||||
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| Target ID |
T53468
(Former ID: TTDI03619)
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| Target Name |
WNK lysine-deficient protein kinase 3 (WNK3)
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| Synonyms |
Serine/threonine-protein kinase WNK3; Protein kinase with no lysine 3; Protein kinase lysine-deficient 3; KIAA1566
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| Gene Name |
WNK3
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MATDSGDPASTEDSEKPDGISFENRVPQVAATLTVEARLKEKNSTFSASGETVERKRFFR
KSVEMTEDDKVAESSPKDERIKAAMNIPRVDKLPSNVLRGGQEVKYEQCSKSTSEISKDC FKEKNEKEMEEEAEMKAVATSPSGRFLKFDIELGRGAFKTVYKGLDTETWVEVAWCELQD RKLTKAEQQRFKEEAEMLKGLQHPNIVRFYDSWESILKGKKCIVLVTELMTSGTLKTYLK RFKVMKPKVLRSWCRQILKGLQFLHTRTPPIIHRDLKCDNIFITGPTGSVKIGDLGLATL MRTSFAKSVIGTPEFMAPEMYEEHYDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRK VTSGIKPASFNKVTDPEVKEIIEGCIRQNKSERLSIRDLLNHAFFAEDTGLRVELAEEDD CSNSSLALRLWVEDPKKLKGKHKDNEAIEFSFNLETDTPEEVAYEMVKSGFFHESDSKAV AKSIRDRVTPIKKTREKKPAGCLEERRDSQCKSMGNVFPQPQNTTLPLAPAQQTGAECEE TEVDQHVRQQLLQRKPQQHCSSVTGDNLSEAGAASVIHSDTSSQPSVAYSSNQTMGSQMV SNIPQAEVNVPGQIYSSQQLVGHYQQVSGLQKHSKLTQPQILPLVQGQSTVLPVHVLGPT VVSQPQVSPLTVQKVPQIKPVSQPVGAEQQAALLKPDLVRSLNQDVATTKENVSSPDNPS GNGKQDRIKQRRASCPRPEKGTKFQLTVLQVSTSGDNMVECQLETHNNKMVTFKFDVDGD APEDIADYMVEDNFVLESEKEKFVEELRAIVGQAQEILHVHFATERATGVDSITVDSNSS QTGSSEQVQINSTSTQTSNESAPQSSPVGRWRFCINQTIRNRETQSPPSLQHSMSAVPGR HPLPSPKNTSNKEISRDTLLTIENNPCHRALFTSKSEHKDVVDGKISECASVETKQPAIL YQVEDNRQIMAPVTNSSSYSTTSVRAVPAECEGLTKQASIFIPVYPCHQTASQADALMSH PGESTQTSGNSLTTLAFDQKPQTLSVQQPAMDAEFISQEGETTVNTEASSPKTVIPTQTP GLEPTTLQPTTVLESDGERPPKLEFADNRIKTLDEKLRNLLYQEHSISSIYPESQKDTQS IDSPFSSSAEDTLSCPVTEVIAISHCGIKDSPVQSPNFQQTGSKLLSNVAASQPANISVF KRDLNVITSVPSELCLHEMSSDASLPGDPEAYPAAVSSGGAIHLQTGGGYFGLSFTCPSL KNPISKKSWTRKLKSWAYRLRQSTSFFKRSKVRQVETEEMRSAIAPDPIPLTRESTADTR ALNRCKAMSGSFQRGRFQVITIPQQQSAKMTSFGIEHISVFSETNHSSEEAFIKTAKSQL VEIEPATQNPKTSFSYEKLQALQETCKENKGVPKQGDNFLSFSAACETDVSSVTPEKEFE ETSATGSSMQSGSELLLKEREILTAGKQPSSDSEFSASLAGSGKSVAKTGPESNQCLPHH EEQAYAQTQSSLFYSPSSPMSSDDESEIEDEDLKVELQRLREKHIQEVVNLQTQQNKELQ ELYERLRSIKDSKTQSTEIPLPPASPRRPRSFKSKLRSRPQSLTHVDNGIVATGKSCLIN ELENPLCVESNAASCQQSPASKKGMFTDDLHKLVDDWTKEAVGNSLIKPSLNQLKQSQHK LETENWNKVSENTPSTMGYTSTWISSLSQIRGAVPTSLPQGLSLPSFPGPLSSYGMPHVC QYNAVAGAGYPVQWVGISGTTQQSVVIPAQSGGPFQPGMNMQAFPTSSVQNPATIPPGPK 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: PP121 | Ligand Info | |||||
| Structure Description | Crystal structure of WNK3 kinase domain in a diphosphorylated state and in a complex with the inhibitor PP-121 | PDB:5O2B | ||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [2] |
| PDB Sequence |
MEAEMKAVAT
140 SPSGRFLKFD150 IELGRGAFKT160 VYKGLDTETW170 VEVAWCELQL183 TKAEQQRFKE 193 EAEMLKGLQH203 PNIVRFYDSW213 ESIKCIVLVT227 ELMTSGTLKT237 YLKRFKVMKP 247 KVLRSWCRQI257 LKGLQFLHTR267 TPPIIHRDLK277 CDNIFITGPT287 GSVKIGDLGL 297 ATLMIGTPEF315 MAPEMYEEHY325 DESVDVYAFG335 MCMLEMATSE345 YPYSECQNAA 355 QIYRKVTSGI365 KPASFNKVTD375 PEVKEIIEGC385 IRQNKSERLS395 IRDLLNHAFF 405 AEDTGLRVE
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GLY154
3.996
ARG155
3.920
GLY156
4.013
LYS159
2.807
VAL161
3.502
ALA174
3.643
CYS176
4.109
VAL207
3.969
LEU225
3.789
THR227
2.996
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| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | Crystal structure of WNK3 kinase domain in a diphosphorylated state and in complex with AMP-PNP/Mg2+ | PDB:5O26 | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [3] |
| PDB Sequence |
MKAVATSPSG
144 RFLKFDIELG154 RGAFKTVYKG164 LDTETWVEVA174 WCELQDTKAE187 QQRFKEEAEM 197 LKGLQHPNIV207 RFYDSWESIK221 CIVLVTELMT231 SGTLKTYLKR241 FKVMKPKVLR 251 SWCRQILKGL261 QFLHTRTPPI271 IHRDLKCDNI281 FITGPTGSVK291 IGDLGLATLM 301 RTFAKVIGTP313 EFMAPEMYEE323 HYDESVDVYA333 FGMCMLEMAT343 SEYPYSECQN 353 AAQIYRKVTS363 GIKPASFNKV373 TDPEVKEIIE383 GCIRQNKSER393 LSIRDLLNHA 403 FFAEDTGLRV413 E
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GLY154
3.777
ARG155
3.706
GLY156
3.377
ALA157
2.966
PHE158
2.824
LYS159
2.933
VAL161
3.418
ALA174
3.823
CYS176
4.801
THR227
4.053
GLU228
3.161
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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 Similarity Proteins
Human Tissue Distribution
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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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| Chemical Structure based Activity Landscape of Target | Top |
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| References | Top | |||||
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| REF 1 | Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9. | |||||
| REF 2 | Crystal structure of WNK3 kinase domain in a diphosphorylated state and in a complex with the inhibitor PP-121 | |||||
| REF 3 | Crystal structure of WNK3 kinase domain in a diphosphorylated state and in complex with AMP-PNP/Mg2+ | |||||
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