Target Information
| Target General Information | Top | |||||
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| Target ID |
T99818
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| Target Name |
HUMAN sodium pump subunit alpha-1 (ATP1A1)
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| Synonyms |
Sodium/potassium-transporting ATPase alpha1; Sodium pump 1; Na+/K+ ATPase 1; ATP1A1
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| Gene Name |
ATP1A1
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Middle East Respiratory Syndrome [ICD-11: 1D64] | |||||
| Function |
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of atp coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions.
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| BioChemical Class |
Acid anhydrides hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 7.2.2.13
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| Sequence |
MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE TYY 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 hemisuccinate | Ligand Info | |||||
| Structure Description | Cryo EM structure of a K+-bound Na+,K+-ATPase in the E2 state | PDB:7E20 | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
RDMDELKKEV
39 SMDDHKLSLD49 ELHRKYGTDL59 SRGLTSARAA69 EILARDGPNA79 LTPPPTTPEW 89 IKFCRQLFGG99 FSMLLWIGAI109 LCFLAYSIQA119 ATEEEPQNDN129 LYLGVVLSAV 139 VIITGCFSYY149 QEAKSSKIME159 SFKNMVPQQA169 LVIRNGEKMS179 INAEEVVVGD 189 LVEVKGGDRI199 PADLRIISAN209 GCKVDNSSLT219 GESEPQTRSP229 DFTNENPLET 239 RNIAFFSTNC249 VEGTARGIVV259 YTGDRTVMGR269 IATLASGLEG279 GQTPIAAEIE 289 HFIHIITGVA299 VFLGVSFFIL309 SLILEYTWLE319 AVIFLIGIIV329 ANVPEGLLAT 339 VTVCLTLTAK349 RMARKNCLVK359 NLEAVETLGS369 TSTICSDKTG379 TLTQNRMTVA 389 HMWFDNQIHE399 ADTTENQSGV409 SFDKTSATWL419 ALSRIAGLCN429 RAVFQANQEN 439 LPILKRAVAG449 DASESALLKC459 IELCCGSVKE469 MRERYAKIVE479 IPFNSTNKYQ 489 LSIHKNPNTS499 EPQHLLVMKG509 APERILDRCS519 SILLHGKEQP529 LDEELKDAFQ 539 NAYLELGGLG549 ERVLGFCHLF559 LPDEQFPEGF569 QFDTDDVNFP579 IDNLCFVGLI 589 SMIDPPRAAV599 PDAVGKCRSA609 GIKVIMVTGD619 HPITAKAIAK629 GVGIISEGNE 639 TVEDIAARLN649 IPVSQVNPRD659 AKACVVHGSD669 LKDMTSEQLD679 DILKYHTEIV 689 FARTSPQQKL699 IIVEGCQRQG709 AIVAVTGDGV719 NDSPALKKAD729 IGVAMGIAGS 739 DVSKQAADMI749 LLDDNFASIV759 TGVEEGRLIF769 DNLKKSIAYT779 LTSNIPEITP 789 FLIFIIANIP799 LPLGTVTILC809 IDLGTDMVPA819 ISLAYEQAES829 DIMKRQPRNP 839 KTDKLVNERL849 ISMAYGQIGM859 IQALGGFFTY869 FVILAENGFL879 PIHLLGLRVD 889 WDDRWINDVE899 DSYGQQWTYE909 QRKIVEFTCH919 TAFFVSIVVV929 QWADLVICKT 939 RRNSVFQQGM949 KNKILIFGLF959 EETALAAFLS969 YCPGMGVALR979 MYPLKPTWWF 989 CAFPYSLLIF999 VYDEVRKLII1009 RRRPGGWVEK1019 ETYY
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ILE784
4.850
THR788
3.884
ILE792
3.876
ILE798
4.788
MET859
2.272
ALA862
3.970
LEU863
3.401
PHE866
3.243
PHE867
3.592
PHE870
3.135
VAL871
4.500
GLU875
2.388
PRO880
3.823
ILE881
2.218
LEU884
3.885
TRP931
4.280
ALA932
4.948
VAL935
3.079
VAL944
3.488
PHE945
3.018
GLN946
4.135
GLN947
3.900
GLY948
3.558
MET949
2.748
LYS950
4.639
THR986
3.584
PHE989
3.805
CYS990
3.522
PHE992
3.742
PRO993
3.919
SER995
3.980
LEU996
4.418
PHE999
2.852
ILE784
3.663
ILE787
4.258
THR788
4.207
GLU847
3.318
ILE850
4.953
SER851
4.451
TYR854
4.112
GLY855
3.754
MET859
2.746
LEU863
4.624
ILE881
4.140
LEU884
3.918
TRP931
3.758
THR962
3.534
TYR970
3.920
PRO985
3.326
TRP988
3.641
PHE989
3.619
PHE992
3.292
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Phosphothiophosphoric acid-adenylate ester | Ligand Info | |||||
| Structure Description | Cryo EM structure of a Na+-bound Na+,K+-ATPase in the E1 state with ATP-gamma-S | PDB:7E21 | ||||
| Method | Electron microscopy | Resolution | 2.90 Å | Mutation | No | [2] |
| PDB Sequence |
SMDDHKLSLD
49 ELHRKYGTDL59 SRGLTSARAA69 EILARDGPNA79 LTPPPTTPEW89 IKFCRQLFGG 99 FSMLLWIGAI109 LCFLAYSIQA119 ATEEEPQNDN129 LYLGVVLSAV139 VIITGCFSYY 149 QEAKSSKIME159 SFKNMVPQQA169 LVIRNGEKMS179 INAEEVVVGD189 LVEVKGGDRI 199 PADLRIISAN209 GCKVDNSSLT219 GESEPQTRSP229 DFTNENPLET239 RNIAFFSTNC 249 VEGTARGIVV259 YTGDRTVMGR269 IAGQTPIAAE287 IEHFIHIITG297 VAVFLGVSFF 307 ILSLILEYTW317 LEAVIFLIGI327 IVANVPEGLL337 ATVTVCLTLT347 AKRMARKNCL 357 VKNLEAVETL367 GSTSTICSDK377 TGTLTQNRMT387 VAHMWFDNQI397 HEADTTENQS 407 GVSFDKTSAT417 WLALSRIAGL427 CNRAVFQANQ437 ENLPILKRAV447 AGDASESALL 457 KCIELCCGSV467 KEMRERYAKI477 VEIPFNSTNK487 YQLSIHKNPN497 TSEPQHLLVM 507 KGAPERILDR517 CSSILLHGKE527 QPLDEELKDA537 FQNAYLELGG547 LGERVLGFCH 557 LFLPDEQFPE567 GFQFDTDDVN577 FPIDNLCFVG587 LISMIDPPRA597 AVPDAVGKCR 607 SAGIKVIMVT617 GDHPITAKAI627 AKGVGIISEG637 NETVEDIAAR647 LNIPVSQVNP 657 RDAKACVVHG667 SDLKDMTSEQ677 LDDILKYHTE687 IVFARTSPQQ697 KLIIVEGCQR 707 QGAIVAVTGD717 GVNDSPALKK727 ADIGVAMGIA737 GSDVSKQAAD747 MILLDDNFAS 757 IVTGVEEGRL767 IFDNLKKSIA777 YTLTSNIPEI787 TPFLIFIIAN797 IPLPLGTVTI 807 LCIDLGTDMV817 PAISLAYEQA827 ESDIMKRQPR837 NPKTDKLVNE847 RLISMAYGQI 857 GMIQALGGFF867 TYFVILAENG877 FLPIHLLGLR887 VDWDDRWIND897 VEDSYGQQWT 907 YEQRKIVEFT917 CHTAFFVSIV927 VVQWADLVIC937 KTRRNSVFQQ947 GMKNKILIFG 957 LFEETALAAF967 LSYCPGMGVA977 LRMYPLKPTW987 WFCAFPYSLL997 IFVYDEVRKL 1007 IIRRRPGGWV1017 EKETYY
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ASP376
3.603
LYS377
3.220
THR378
3.260
ASP450
3.593
SER452
3.990
GLU453
4.531
PHE482
3.184
SER484
3.861
LYS487
3.692
TYR488
4.533
GLN489
4.038
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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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| cGMP-PKG signaling pathway | hsa04022 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| cAMP signaling pathway | hsa04024 | 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 | ||
| Adrenergic signaling in cardiomyocytes | hsa04261 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Insulin secretion | hsa04911 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Thyroid hormone synthesis | hsa04918 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Thyroid hormone signaling pathway | hsa04919 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Aldosterone synthesis and secretion | hsa04925 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Aldosterone-regulated sodium reabsorption | hsa04960 | Affiliated Target |
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| Class: Organismal Systems => Excretory system | Pathway Hierarchy | ||
| Endocrine and other factor-regulated calcium reabsorption | hsa04961 | Affiliated Target |
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| Class: Organismal Systems => Excretory system | Pathway Hierarchy | ||
| Proximal tubule bicarbonate reclamation | hsa04964 | Affiliated Target |
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| Class: Organismal Systems => Excretory system | Pathway Hierarchy | ||
| Salivary secretion | hsa04970 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Gastric acid secretion | hsa04971 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Pancreatic secretion | hsa04972 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Carbohydrate digestion and absorption | hsa04973 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Protein digestion and absorption | hsa04974 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Bile secretion | hsa04976 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Mineral absorption | hsa04978 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 7.74E-08 |
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| Closeness centrality | 1.27E-01 | Radiality | 1.09E+01 | Clustering coefficient | 1.67E-01 |
| Neighborhood connectivity | 4.00E+00 | Topological coefficient | 5.83E-01 | Eccentricity | 15 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| References | Top | |||||
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| REF 1 | The 14-3-3 Protein Translates the NA+,K+-ATPase {alpha}1-subunit Phosphorylation Signal Into Binding and Activation of Phosphoinositide 3-kinase During Endocytosis J Biol Chem. 2005 Apr 22;280(16):16272-7. | |||||
| REF 2 | Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states. Nat Commun. 2022 Jul 8;13(1):3957. | |||||
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