Target Information
| Target General Information | Top | |||||
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| Target ID |
T75545
(Former ID: TTDR01199)
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| Target Name |
Solute carrier family 12 member 6 (SLC12A6)
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| Synonyms |
SLC12A6; Electroneutral potassium-chloride cotransporter 3
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| Gene Name |
SLC12A6
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.
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| BioChemical Class |
Cation-chloride cotransporter
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| UniProt ID | ||||||
| Sequence |
MHPPETTTKMASVRFMVTPTKIDDIPGLSDTSPDLSSRSSSRVRFSSRESVPETSRSEPM
SEMSGATTSLATVALDPPSDRTSHPQDVIEDLSQNSITGEHSQLLDDGHKKARNAYLNNS NYEEGDEYFDKNLALFEEEMDTRPKVSSLLNRMANYTNLTQGAKEHEEAENITEGKKKPT KTPQMGTFMGVYLPCLQNIFGVILFLRLTWVVGTAGVLQAFAIVLICCCCTMLTAISMSA IATNGVVPAGGSYFMISRALGPEFGGAVGLCFYLGTTFAAAMYILGAIEIFLVYIVPRAA IFHSDDALKESAAMLNNMRVYGTAFLVLMVLVVFIGVRYVNKFASLFLACVIVSILAIYA GAIKSSFAPPHFPVCMLGNRTLSSRHIDVCSKTKEINNMTVPSKLWGFFCNSSQFFNATC DEYFVHNNVTSIQGIPGLASGIITENLWSNYLPKGEIIEKPSAKSSDVLGSLNHEYVLVD ITTSFTLLVGIFFPSVTGIMAGSNRSGDLKDAQKSIPIGTILAILTTSFVYLSNVVLFGA CIEGVVLRDKFGDAVKGNLVVGTLSWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAIAK DNIIPFLRVFGHSKANGEPTWALLLTAAIAELGILIASLDLVAPILSMFFLMCYLFVNLA CALQTLLRTPNWRPRFRYYHWALSFMGMSICLALMFISSWYYAIVAMVIAGMIYKYIEYQ GAEKEWGDGIRGLSLSAARFALLRLEEGPPHTKNWRPQLLVLLKLDEDLHVKHPRLLTFA SQLKAGKGLTIVGSVIVGNFLENYGEALAAEQTIKHLMEAEKVKGFCQLVVAAKLREGIS HLIQSCGLGGMKHNTVVMGWPNGWRQSEDARAWKTFIGTVRVTTAAHLALLVAKNISFFP SNVEQFSEGNIDVWWIVHDGGMLMLLPFLLKQHKVWRKCSIRIFTVAQLEDNSIQMKKDL ATFLYHLRIEAEVEVVEMHDSDISAYTYERTLMMEQRSQMLRHMRLSKTERDREAQLVKD RNSMLRLTSIGSDEDEETETYQEKVHMTWTKDKYMASRGQKAKSMEGFQDLLNMRPDQSN VRRMHTAVKLNEVIVNKSHEAKLVLLNMPGPPRNPEGDENYMEFLEVLTEGLERVLLVRG GGSEVITIYS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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-[[(2~{R})-2-butyl-6,7-bis(chloranyl)-2-cyclopentyl-1-oxidanylidene-3~{H}-inden-5-yl]oxy]ethanoic acid | Ligand Info | |||||
| Structure Description | KCC3 bound with DIOA | PDB:6M22 | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
YTNLTQGAKE
114 HEEQMGTFMG139 VYLPCLQNIF149 GVILFLRLTW159 VVGTAGVLQA169 FAIVLICCCC 179 TMLTAISMSA189 IATNGVVPAG199 GSYFMISRAL209 GPEFGGAVGL219 CFYLGTTFAA 229 AMYILGAIEI239 FLVYIVPRAA249 IFHSDDALKE259 SAAMLNNMRV269 YGTAFLVLMV 279 LVVFIGVRYV289 NKFASLFLAC299 VIVSILAIYA309 GAIKSSFAPP319 HFPVCMLGNR 329 TLSSRHIDVC339 SKTKEINNMT349 VPSKLWGFFC359 NSSQFFNATC369 DEYFVHNNVT 379 SIQGIPGLAS389 GIITENLWSN399 YLPKGEIIEK409 PSAKSSDVLG419 SLNHEYVLVD 429 ITTSFTLLVG439 IFFPSVTGIM449 AGSNRSGDLK459 DAQKSIPIGT469 ILAILTTSFV 479 YLSNVVLFGA489 CIEGVVLRDK499 FGDAVKGNLV509 VGTLSWPSPW519 VIVIGSFFST 529 CGAGLQSLTG539 APRLLQAIAK549 DNIIPFLRVF559 GHSKANGEPT569 WALLLTAAIA 579 ELGILIASLD589 LVAPILSMFF599 LMCYLFVNLA609 CALQTLLRTP619 NWRPRFRYYH 629 WALSFMGMSI639 CLALMFISSW649 YYAIVAMVIA659 GMIYKYIEYQ669 GAEKEWGDGI 679 RGLSLSAARF689 ALLRLEEGPP699 HTKNWRPQLL709 VLLKLDEDLH719 VKHPRLLTFA 729 SQLKAGKGLT739 IVGSVIVGNF749 LENYGEALAA759 EQTIKHLMEA769 EKVKGFCQLV 779 VAAKLREGIS789 HLIQSCGLGG799 MKHNTVVMGW809 PNGWRQSEDA819 RAWKTFIGTV 829 RVTTAAHLAL839 LVAKNISFFP849 SNVEQFSEGN859 IDVWWIVHDG869 GMLMLLPFLL 879 KQHKVWRKCS889 IRIFTVAQLE899 DNSIQMKKDL909 ATFLYHLRIE919 AEVEVVEMHD 929 SDISNVRRMH1034 TAVKLNEVIV1044 NKSHEAKLVL1054 LNMPGPPRNP1064 EGDENYMEFL 1074 EVLTEGLERV1084 LLVRGGGSEV1094 ITIYS
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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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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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| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | FSH Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Cation-coupled Chloride cotransporters | |||||
| References | Top | |||||
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| REF 1 | 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. (Target id: 973). | |||||
| REF 2 | Cryo-EM structures of the full-length human KCC2 and KCC3 cation-chloride cotransporters. Cell Res. 2021 Apr;31(4):482-484. | |||||
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