Details of the Target

General Information of Target

Target ID LDTP04459
Target Name H(+)/Cl(-) exchange transporter 3 (CLCN3)
Gene Name CLCN3
Gene ID 1182
Synonyms
H(+)/Cl(-) exchange transporter 3; Chloride channel protein 3; ClC-3; Chloride transporter ClC-3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQTSEDDNLLDGDTAVGTHYTMT
NGGSINSSTHLLDLLDEPIPGVGTYDDFHTIDWVREKCKDRERHRRINSKKKESAWEMTK
SLYDAWSGWLVVTLTGLASGALAGLIDIAADWMTDLKEGICLSALWYNHEQCCWGSNETT
FEERDKCPQWKTWAELIIGQAEGPGSYIMNYIMYIFWALSFAFLAVSLVKVFAPYACGSG
IPEIKTILSGFIIRGYLGKWTLMIKTITLVLAVASGLSLGKEGPLVHVACCCGNIFSYLF
PKYSTNEAKKREVLSAASAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAA
FVLRSINPFGNSRLVLFYVEYHTPWYLFELFPFILLGVFGGLWGAFFIRANIAWCRRRKS
TKFGKYPVLEVIIVAAITAVIAFPNPYTRLNTSELIKELFTDCGPLESSSLCDYRNDMNA
SKIVDDIPDRPAGIGVYSAIWQLCLALIFKIIMTVFTFGIKVPSGLFIPSMAIGAIAGRI
VGIAVEQLAYYHHDWFIFKEWCEVGADCITPGLYAMVGAAACLGGVTRMTVSLVVIVFEL
TGGLEYIVPLMAAVMTSKWVGDAFGREGIYEAHIRLNGYPFLDAKEEFTHTTLAADVMRP
RRNDPPLAVLTQDNMTVDDIENMINETSYNGFPVIMSKESQRLVGFALRRDLTIAIESAR
KKQEGIVGSSRVCFAQHTPSLPAESPRPLKLRSILDMSPFTVTDHTPMEIVVDIFRKLGL
RQCLVTHNGRLLGIITKKDILRHMAQTANQDPASIMFN
Target Type
Literature-reported
Target Bioclass
Transporter and channel
Family
Chloride channel (TC 2.A.49) family, ClC-3/CLCN3 subfamily
Subcellular location
Early endosome membrane; Golgi apparatus membrane
Function
[Isoform 1]: Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters.; [Isoform 2]: Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons.
TTD ID
T60671
Uniprot ID
P51790
DrugMap ID
TT8XNZ7
Ensemble ID
ENST00000347613.9
HGNC ID
HGNC:2021
ChEMBL ID
CHEMBL2401603

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CAL120 SNV: p.R539S DBIA    Probe Info 
CHL1 SNV: p.P491S DBIA    Probe Info 
HCT116 Deletion: p.D799IfsTer17 .
HEC1 SNV: p.V428I DBIA    Probe Info 
HEC1B SNV: p.V428I .
Ishikawa (Heraklio) 02 ER SNV: p.I508M DBIA    Probe Info 
KPL1 SNV: p.W555Ter DBIA    Probe Info 
MCF7 SNV: p.W555Ter .
MDAMB453 SNV: p.L376I DBIA    Probe Info 
MOLT4 SNV: p.T192I .
NCIH1155 SNV: p.T514I DBIA    Probe Info 
NCIH2172 SNV: p.Y256F .
NCIH3122 SNV: p.I695V DBIA    Probe Info 
OVK18 SNV: p.E26D DBIA    Probe Info 
SG231 SNV: p.D485N DBIA    Probe Info 
SKN SNV: p.V379M DBIA    Probe Info 
SNGM SNV: p.A579V DBIA    Probe Info 
SNU1 Deletion: p.R311GfsTer14 DBIA    Probe Info 
SUPT1 SNV: p.G565R DBIA    Probe Info 
SW1271 SNV: p.R184S .
SW620 SNV: p.E26K DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 7 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C733(1.64)  LDD3310  [1]
BTD
 Probe Info  		C783(0.65)  LDD2091  [2]
FBPP2
 Probe Info  		2.36  LDD0054  [3]
IA-alkyne
 Probe Info  		C783(0.00); C733(0.00)  LDD0036  [4]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [4]
IPM
 Probe Info  		N.A.  LDD0025  [5]
NAIA_5
 Probe Info  		N.A.  LDD2224  [6]
PAL-AfBPP Probe
Click To Hide/Show 44 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C040
 Probe Info  		8.28  LDD1740  [7]
C063
 Probe Info  		10.06  LDD1760  [7]
C091
 Probe Info  		10.20  LDD1782  [7]
C095
 Probe Info  		5.31  LDD1786  [7]
C100
 Probe Info  		6.15  LDD1789  [7]
C107
 Probe Info  		6.54  LDD1794  [7]
C112
 Probe Info  		19.43  LDD1799  [7]
C141
 Probe Info  		9.78  LDD1823  [7]
C143
 Probe Info  		12.82  LDD1825  [7]
C149
 Probe Info  		5.10  LDD1830  [7]
C159
 Probe Info  		9.00  LDD1839  [7]
C160
 Probe Info  		8.00  LDD1840  [7]
C161
 Probe Info  		15.03  LDD1841  [7]
C170
 Probe Info  		31.12  LDD1850  [7]
C177
 Probe Info  		7.62  LDD1856  [7]
C178
 Probe Info  		15.14  LDD1857  [7]
C186
 Probe Info  		15.45  LDD1864  [7]
C187
 Probe Info  		16.91  LDD1865  [7]
C197
 Probe Info  		10.56  LDD1873  [7]
C198
 Probe Info  		14.03  LDD1874  [7]
C201
 Probe Info  		33.36  LDD1877  [7]
C208
 Probe Info  		10.27  LDD1883  [7]
C218
 Probe Info  		11.47  LDD1892  [7]
C219
 Probe Info  		5.35  LDD1893  [7]
C221
 Probe Info  		5.90  LDD1895  [7]
C223
 Probe Info  		4.92  LDD1897  [7]
C231
 Probe Info  		18.64  LDD1904  [7]
C235
 Probe Info  		22.32  LDD1908  [7]
C237
 Probe Info  		5.90  LDD1910  [7]
C243
 Probe Info  		14.52  LDD1916  [7]
C246
 Probe Info  		17.75  LDD1919  [7]
C277
 Probe Info  		7.84  LDD1947  [7]
C281
 Probe Info  		5.94  LDD1951  [7]
C310
 Probe Info  		11.79  LDD1977  [7]
C326
 Probe Info  		7.62  LDD1990  [7]
C349
 Probe Info  		9.00  LDD2010  [7]
C350
 Probe Info  		25.99  LDD2011  [7]
C355
 Probe Info  		36.00  LDD2016  [7]
C356
 Probe Info  		13.18  LDD2017  [7]
C386
 Probe Info  		6.50  LDD2045  [7]
C388
 Probe Info  		38.85  LDD2047  [7]
C390
 Probe Info  		21.71  LDD2049  [7]
C420
 Probe Info  		10.13  LDD2075  [7]
C425
 Probe Info  		7.11  LDD2080  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0558  2-Cyano-N-phenylacetamide MDA-MB-231 C733(0.50)  LDD2152  [2]
 LDCM0498  BS-3668 MDA-MB-231 C783(0.65)  LDD2091  [2]
 LDCM0625  F8 Ramos C237(1.36); C733(1.41)  LDD2187  [8]
 LDCM0572  Fragment10 Ramos C237(0.82); C733(1.04)  LDD2189  [8]
 LDCM0573  Fragment11 Ramos C237(2.82); C733(3.25)  LDD2190  [8]
 LDCM0574  Fragment12 Ramos C237(1.13); C733(0.66)  LDD2191  [8]
 LDCM0575  Fragment13 Ramos C237(0.97); C733(1.00)  LDD2192  [8]
 LDCM0576  Fragment14 Ramos C237(1.45); C733(0.80)  LDD2193  [8]
 LDCM0579  Fragment20 Ramos C733(0.54)  LDD2194  [8]
 LDCM0580  Fragment21 Ramos C237(0.96); C733(0.64)  LDD2195  [8]
 LDCM0582  Fragment23 Ramos C237(1.11); C733(0.80)  LDD2196  [8]
 LDCM0578  Fragment27 Ramos C237(0.60); C733(0.53)  LDD2197  [8]
 LDCM0586  Fragment28 Ramos C237(0.71); C733(0.23)  LDD2198  [8]
 LDCM0588  Fragment30 Ramos C237(0.81); C733(0.64)  LDD2199  [8]
 LDCM0589  Fragment31 Ramos C237(1.01); C733(0.58)  LDD2200  [8]
 LDCM0590  Fragment32 Ramos C237(0.94); C733(3.37)  LDD2201  [8]
 LDCM0468  Fragment33 Ramos C237(1.58); C733(0.78)  LDD2202  [8]
 LDCM0596  Fragment38 Ramos C237(0.80); C733(0.65)  LDD2203  [8]
 LDCM0566  Fragment4 Ramos C237(1.11); C733(1.11)  LDD2184  [8]
 LDCM0610  Fragment52 Ramos C237(1.34); C733(0.39)  LDD2204  [8]
 LDCM0614  Fragment56 Ramos C237(0.99); C733(0.77)  LDD2205  [8]
 LDCM0569  Fragment7 Ramos C237(0.91); C733(0.98)  LDD2186  [8]
 LDCM0571  Fragment9 Ramos C733(0.85)  LDD2188  [8]
 LDCM0022  KB02 HEK-293T C733(1.02); C237(1.03)  LDD1492  [9]
 LDCM0023  KB03 HEK-293T C733(0.98); C237(0.99)  LDD1497  [9]
 LDCM0024  KB05 COLO792 C733(1.64)  LDD3310  [1]
 LDCM0528  N-(4-bromophenyl)-2-cyano-N-phenylacetamide MDA-MB-231 C733(1.01)  LDD2121  [2]
 LDCM0501  Nucleophilic fragment 13b MDA-MB-231 C783(1.74)  LDD2094  [2]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C733(0.91)  LDD2104  [2]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C783(1.66)  LDD2107  [2]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C733(0.51)  LDD2120  [2]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C733(1.10)  LDD2135  [2]
 LDCM0549  Nucleophilic fragment 43 MDA-MB-231 C733(0.66)  LDD2143  [2]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C733(0.66); C783(0.63)  LDD2150  [2]
 LDCM0008  Tranylcypromine SH-SY5Y 2.36  LDD0054  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cystic fibrosis transmembrane conductance regulator (CFTR) ABCC family P13569
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Na(+)/H(+) exchange regulatory cofactor NHE-RF3 (PDZK1) NHER family Q5T2W1

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phloretin Small molecular drug D0HD2G

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
4 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
5 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
6 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
7 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
8 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
9 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402