Target Information
| Target General Information | Top | |||||
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| Target ID |
T43531
(Former ID: TTDI03370)
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| Target Name |
Chloride channel protein 7 (ClC-7)
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| Synonyms |
H(+)/Cl(-) exchange transporter 7; ClC-7; Chloride channel 7 alpha subunit
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| Gene Name |
CLCN7
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Slowly voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the lysosome lumen.
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| BioChemical Class |
Chloride channel
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| UniProt ID | ||||||
| Sequence |
MANVSKKVSWSGRDRDDEEAAPLLRRTARPGGGTPLLNGAGPGAARQSPRSALFRVGHMS
SVELDDELLDPDMDPPHPFPKEIPHNEKLLSLKYESLDYDNSENQLFLEEERRINHTAFR TVEIKRWVICALIGILTGLVACFIDIVVENLAGLKYRVIKGNIDKFTEKGGLSFSLLLWA TLNAAFVLVGSVIVAFIEPVAAGSGIPQIKCFLNGVKIPHVVRLKTLVIKVSGVILSVVG GLAVGKEGPMIHSGSVIAAGISQGRSTSLKRDFKIFEYFRRDTEKRDFVSAGAAAGVSAA FGAPVGGVLFSLEEGASFWNQFLTWRIFFASMISTFTLNFVLSIYHGNMWDLSSPGLINF GRFDSEKMAYTIHEIPVFIAMGVVGGVLGAVFNALNYWLTMFRIRYIHRPCLQVIEAVLV AAVTATVAFVLIYSSRDCQPLQGGSMSYPLQLFCADGEYNSMAAAFFNTPEKSVVSLFHD PPGSYNPLTLGLFTLVYFFLACWTYGLTVSAGVFIPSLLIGAAWGRLFGISLSYLTGAAI WADPGKYALMGAAAQLGGIVRMTLSLTVIMMEATSNVTYGFPIMLVLMTAKIVGDVFIEG LYDMHIQLQSVPFLHWEAPVTSHSLTAREVMSTPVTCLRRREKVGVIVDVLSDTASNHNG FPVVEHADDTQPARLQGLILRSQLIVLLKHKVFVERSNLGLVQRRLRLKDFRDAYPRFPP IQSIHVSQDERECTMDLSEFMNPSPYTVPQEASLPRVFKLFRALGLRHLVVVDNRNQVVG LVTRKDLARYRLGKRGLEELSLAQT 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 the human CLCN7-OSTM1 complex with ATP | PDB:7CQ5 | ||||
| Method | Electron microscopy | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
YESLDYDNSE
103 NQLFLEEERR113 INHTAFRTVE123 IKRWVICALI133 GILTGLVACF143 IDIVVENLAG 153 LKYRVIKGNI163 DKFTEKGGLS173 FSLLLWATLN183 AAFVLVGSVI193 VAFIEPVAAG 203 SGIPQIKCFL213 NGVKIPHVVR223 LKTLVIKVSG233 VILSVVGGLA243 VGKEGPMIHS 253 GSVIAAGISQ263 GRSTSLKRDF273 KIFEYFRRDT283 EKRDFVSAGA293 AAGVSAAFGA 303 PVGGVLFSLE313 EGASFWNQFL323 TWRIFFASMI333 STFTLNFVLS343 IYHGNMWDLS 353 SPGLINFGRF363 DSEKMAYTIH373 EIPVFIAMGV383 VGGVLGAVFN393 ALNYWLTMFR 403 IRYIHRPCLQ413 VIEAVLVAAV423 TATVAFVLIY433 SSRDCQPLQG443 GSMSYPLQLF 453 CADGEYNSMA463 AAFFNTPEKS473 VVSLFHDPPG483 SYNPLTLGLF493 TLVYFFLACW 503 TYGLTVSAGV513 FIPSLLIGAA523 WGRLFGISLS533 YLTGAAIWAD543 PGKYALMGAA 553 AQLGGIVRMT563 LSLTVIMMEA573 TSNVTYGFPI583 MLVLMTAKIV593 GDVFIEGLYD 603 MHIQLQSVPF613 LHWEAPVTSH623 SLTAREVMST633 PVTCLRRREK643 VGVIVDVLSD 653 TASNHNGFPV663 VEARLQGLIL680 RSQLIVLLKH690 KVFVRRLRLK709 DFRDAYPRFP 719 PIQSIHVSQD729 ERECTMDLSE739 FMNPSPYTVP749 QEASLPRVFK759 LFRALGLRHL 769 VVVDNRNQVV779 GLVTRKDLAR789 Y
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TYR94
3.804
GLU95
3.371
SER96
2.983
SER632
3.269
PRO634
3.597
VAL635
3.869
THR636
3.293
SER656
4.104
ASN657
3.253
HIS658
2.627
ASN659
2.775
GLY660
2.529
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Structure of the human CLCN7-OSTM1 complex with ADP | PDB:7CQ7 | ||||
| Method | Electron microscopy | Resolution | 3.55 Å | Mutation | No | [4] |
| PDB Sequence |
YESLDYDNSE
103 NQLFLEEERR113 INHTVEIKRW127 VICALIGILT137 GLVACFIDIV147 VENLAGLKYR 157 VIKGNIDKFT167 EKGGLSFSLL177 LWATLNAAFV187 LVGSVIVAFI197 EPVAAGSGIP 207 QIKCFLNGVK217 IPHVVRLKTL227 VIKVSGVILS237 VVGGLAVGKE247 GPMIHSGSVI 257 AAGISQGRST267 SLKRDFKIFE277 YFRRDTEKRD287 FVSAGAAAGV297 SAAFGAPVGG 307 VLFSLEEGAS317 FWNQFLTWRI327 FFASMISTFT337 LNFVLSIYHG347 NMWDLSSPGL 357 INFGRFDSEK367 MAYTIHEIPV377 FIAMGVVGGV387 LGAVFNALNY397 WLTMFRIRYI 407 HRPCLQVIEA417 VLVAAVTATV427 AFVLIYSSRD437 CQPLQGGSMS447 YPLQLFCADG 457 EYNSMAAAFF467 NTPEKSVVSL477 FHDPPGSYNP487 LTLGLFTLVY497 FFLACWTYGL 507 TVSAGVFIPS517 LLIGAAWGRL527 FGISLSYLTG537 AAIWADPGKY547 ALMGAAAQLG 557 GIVRMTLSLT567 VIMMEATSNV577 TYGFPIMLVL587 MTAKIVGDVF597 IEGLYDMHIQ 607 LQSVPFLHWE617 APVTSHSLTA627 REVMSTPVTC637 LRRREKVGVI647 VDVLSDTASN 657 HNGFPVVEAR674 LQGLILRSQL684 IVLLKHKVFR704 RLRLKDFRDA714 YPRFPPIQSI 724 HVSQDERECT734 MDLSEFMNPS744 PYTVPQEASL754 PRVFKLFRAL764 GLRHLVVVDN 774 RNQVVGLVTR784 KDLARY
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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).
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
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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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| 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: 709). | |||||
| REF 2 | The G215R mutation in the Cl-/H+-antiporter ClC-7 found in ADO II osteopetrosis does not abolish function but causes a severe trafficking defect. PLoS One. 2010 Sep 7;5(9):e12585. | |||||
| REF 3 | Structure of the human CLCN7-OSTM1 complex with ATP | |||||
| REF 4 | Structure of the human CLCN7-OSTM1 complex with ADP | |||||
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