Target Information
| Target General Information | Top | |||||
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| Target ID |
T58890
(Former ID: TTDI03312)
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| Target Name |
Solute carrier family 12 member 4 (SLC12A4)
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| Synonyms |
hKCC1; KCC1; Erythroid K-Cl cotransporter 1; Electroneutral potassium-chloride cotransporter 1
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| Gene Name |
SLC12A4
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.
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| UniProt ID | ||||||
| Sequence |
MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSDGHGNHRESSPFLSPLEASRGID
YYDRNLALFEEELDIRPKVSSLLGKLVSYTNLTQGAKEHEEAESGEGTRRRAAEAPSMGT LMGVYLPCLQNIFGVILFLRLTWMVGTAGVLQALLIVLICCCCTLLTAISMSAIATNGVV PAGGSYFMISRSLGPEFGGAVGLCFYLGTTFAAAMYILGAIEILLTYIAPPAAIFYPSGA HDTSNATLNNMRVYGTIFLTFMTLVVFVGVKYVNKFASLFLACVIISILSIYAGGIKSIF DPPVFPVCMLGNRTLSRDQFDICAKTAVVDNETVATQLWSFFCHSPNLTTDSCDPYFMLN NVTEIPGIPGAAAGVLQENLWSAYLEKGDIVEKHGLPSADAPSLKESLPLYVVADIATSF TVLVGIFFPSVTGIMAGSNRSGDLRDAQKSIPVGTILAIITTSLVYFSSVVLFGACIEGV VLRDKYGDGVSRNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAIAKDNIIP FLRVFGHGKVNGEPTWALLLTALIAELGILIASLDMVAPILSMFFLMCYLFVNLACAVQT LLRTPNWRPRFKYYHWALSFLGMSLCLALMFVSSWYYALVAMLIAGMIYKYIEYQGAEKE WGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLLKLDEDLHVKYPRLLTFASQLKA GKGLTIVGSVIQGSFLESYGEAQAAEQTIKNMMEIEKVKGFCQVVVASKVREGLAHLIQS CGLGGMRHNSVVLGWPYGWRQSEDPRAWKTFIDTVRCTTAAHLALLVPKNIAFYPSNHER YLEGHIDVWWIVHDGGMLMLLPFLLRQHKVWRKCRMRIFTVAQMDDNSIQMKKDLAVFLY HLRLEAEVEVVEMHNSDISAYTYERTLMMEQRSQMLRQMRLTKTEREREAQLVKDRHSAL RLESLYSDEEDESAVGADKIQMTWTRDKYMTETWDPSHAPDNFRELVHIKPDQSNVRRMH TAVKLNEVIVTRSHDARLVLLNMPGPPRNSEGDENYMEFLEVLTEGLERVLLVRGGGREV ITIYS 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: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Structure of Human Potassium Chloride Transporter KCC1 in NaCl (Reference Map) | PDB:7AIP | ||||
| Method | Electron microscopy | Resolution | 3.12 Å | Mutation | No | [2] |
| PDB Sequence |
PSMGTLMGVY
125 LPCLQNIFGV135 ILFLRLTWMV145 GTAGVLQALL155 IVLICCCCTL165 LTAISMSAIA 175 TNGVVPAGGS185 YFMISRSLGP195 EFGGAVGLCF205 YLGTTFAAAM215 YILGAIEILL 225 TYIAPPAAIF235 YSNATLNNMR252 VYGTIFLTFM262 TLVVFVGVKY272 VNKFASLFLA 282 CVIISILSIY292 AGGIKSIFDP302 PVFPVCMLGN312 RTLSRDQFDI322 CAKTAVVDNE 332 TVATQLWSFF342 CHSPNLTTDS352 CDPYFMLNNV362 TEIPGIPGAA372 AGVLQENLWS 382 AYLEKGDIVE392 KHGLPSADAP402 SLKESLPLYV412 VADIATSFTV422 LVGIFFPSVT 432 GIMAGSNRSG442 DLRDAQKSIP452 VGTILAIITT462 SLVYFSSVVL472 FGACIEGVVL 482 RDKYGDGVSR492 NLVVGTLAWP502 SPWVIVIGSF512 FSTCGAGLQS522 LTGAPRLLQA 532 IAKDNIIPFL542 RVFGHGKVNG552 EPTWALLLTA562 LIAELGILIA572 SLDMVAPILS 582 MFFLMCYLFV592 NLACAVQTLL602 RTPNWRPRFK612 YYHWALSFLG622 MSLCLALMFV 632 SSWYYALVAM642 LIAGMIYKYI652 EYQGAEKEWG662 DGIRGLSLSA672 ARYALLRLEE 682 GPPHTKNWRP692 QLLVLLKLDE702 DLHVKYPRLL712 TFASQLKAGK722 GLTIVGSVIQ 732 GFLESYGEAQ743 AAEQTIKNMM753 EIEKVKGFCQ763 VVVASKVREG773 LAHLIQSCGL 783 GGMRHNSVVL793 GWPYGWRQSE803 DPRAWKTFID813 TVRCTTAAHL823 ALLVPKNIAF 833 YPSNHERYLE843 GHIDVWWIVH853 DGGMLMLLPF863 LLRQHKVWRK873 CRMRIFTVNS 888 IQMKKDLAVF898 LYHLRLEAEV908 EVVEMHNDIS919 AYTYERTSNV1016 RRMHTAVKLN 1026 EVIVTRSHDA1036 RLVLLNMPGP1046 PRNSEGDENY1056 MEFLEVLTEG1066 LERVLLVRGG 1076 GREVI
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LEU697
2.791
LEU698
2.850
LYS699
3.134
LEU700
4.903
LYS707
3.400
TYR708
2.912
GLY728
4.986
SER729
3.881
VAL730
3.115
VAL770
3.205
LEU774
3.520
LEU793
3.714
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: L-serine-O-phosphate | Ligand Info | |||||
| Structure Description | Structure of Human Potassium Chloride Transporter KCC1 in NaCl (Reference Map) | PDB:7AIP | ||||
| Method | Electron microscopy | Resolution | 3.12 Å | Mutation | No | [2] |
| PDB Sequence |
PSMGTLMGVY
125 LPCLQNIFGV135 ILFLRLTWMV145 GTAGVLQALL155 IVLICCCCTL165 LTAISMSAIA 175 TNGVVPAGGS185 YFMISRSLGP195 EFGGAVGLCF205 YLGTTFAAAM215 YILGAIEILL 225 TYIAPPAAIF235 YSNATLNNMR252 VYGTIFLTFM262 TLVVFVGVKY272 VNKFASLFLA 282 CVIISILSIY292 AGGIKSIFDP302 PVFPVCMLGN312 RTLSRDQFDI322 CAKTAVVDNE 332 TVATQLWSFF342 CHSPNLTTDS352 CDPYFMLNNV362 TEIPGIPGAA372 AGVLQENLWS 382 AYLEKGDIVE392 KHGLPSADAP402 SLKESLPLYV412 VADIATSFTV422 LVGIFFPSVT 432 GIMAGSNRSG442 DLRDAQKSIP452 VGTILAIITT462 SLVYFSSVVL472 FGACIEGVVL 482 RDKYGDGVSR492 NLVVGTLAWP502 SPWVIVIGSF512 FSTCGAGLQS522 LTGAPRLLQA 532 IAKDNIIPFL542 RVFGHGKVNG552 EPTWALLLTA562 LIAELGILIA572 SLDMVAPILS 582 MFFLMCYLFV592 NLACAVQTLL602 RTPNWRPRFK612 YYHWALSFLG622 MSLCLALMFV 632 SSWYYALVAM642 LIAGMIYKYI652 EYQGAEKEWG662 DGIRGLSLSA672 ARYALLRLEE 682 GPPHTKNWRP692 QLLVLLKLDE702 DLHVKYPRLL712 TFASQLKAGK722 GLTIVGSVIQ 732 GFLESYGEAQ743 AAEQTIKNMM753 EIEKVKGFCQ763 VVVASKVREG773 LAHLIQSCGL 783 GGMRHNSVVL793 GWPYGWRQSE803 DPRAWKTFID813 TVRCTTAAHL823 ALLVPKNIAF 833 YPSNHERYLE843 GHIDVWWIVH853 DGGMLMLLPF863 LLRQHKVWRK873 CRMRIFTVNS 888 IQMKKDLAVF898 LYHLRLEAEV908 EVVEMHNDIS919 AYTYERTSNV1016 RRMHTAVKLN 1026 EVIVTRSHDA1036 RLVLLNMPGP1046 PRNSEGDENY1056 MEFLEVLTEG1066 LERVLLVRGG 1076 GREVI
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Cationic amino acid transporter 2 (SLC7A2) | 24.257 (49/202) | 1.00E-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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| 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: 971). | |||||
| REF 2 | Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters. EMBO J. 2021 Jul 15;40(14):e107294. | |||||
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