Details of the Target

General Information of Target

Target ID LDTP09418
Target Name Transient receptor potential cation channel subfamily M member 4 (TRPM4)
Gene Name TRPM4
Gene ID 54795
Synonyms
LTRPC4; Transient receptor potential cation channel subfamily M member 4; hTRPM4; Calcium-activated non-selective cation channel 1; Long transient receptor potential channel 4; LTrpC-4; LTrpC4; Melastatin-4
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MVVPEKEQSWIPKIFKKKTCTTFIVDSTDPGGTLCQCGRPRTAHPAVAMEDAFGAAVVTV
WDSDAHTTEKPTDAYGELDFTGAGRKHSNFLRLSDRTDPAAVYSLVTRTWGFRAPNLVVS
VLGGSGGPVLQTWLQDLLRRGLVRAAQSTGAWIVTGGLHTGIGRHVGVAVRDHQMASTGG
TKVVAMGVAPWGVVRNRDTLINPKGSFPARYRWRGDPEDGVQFPLDYNYSAFFLVDDGTH
GCLGGENRFRLRLESYISQQKTGVGGTGIDIPVLLLLIDGDEKMLTRIENATQAQLPCLL
VAGSGGAADCLAETLEDTLAPGSGGARQGEARDRIRRFFPKGDLEVLQAQVERIMTRKEL
LTVYSSEDGSEEFETIVLKALVKACGSSEASAYLDELRLAVAWNRVDIAQSELFRGDIQW
RSFHLEASLMDALLNDRPEFVRLLISHGLSLGHFLTPMRLAQLYSAAPSNSLIRNLLDQA
SHSAGTKAPALKGGAAELRPPDVGHVLRMLLGKMCAPRYPSGGAWDPHPGQGFGESMYLL
SDKATSPLSLDAGLGQAPWSDLLLWALLLNRAQMAMYFWEMGSNAVSSALGACLLLRVMA
RLEPDAEEAARRKDLAFKFEGMGVDLFGECYRSSEVRAARLLLRRCPLWGDATCLQLAMQ
ADARAFFAQDGVQSLLTQKWWGDMASTTPIWALVLAFFCPPLIYTRLITFRKSEEEPTRE
ELEFDMDSVINGEGPVGTADPAEKTPLGVPRQSGRPGCCGGRCGGRRCLRRWFHFWGAPV
TIFMGNVVSYLLFLLLFSRVLLVDFQPAPPGSLELLLYFWAFTLLCEELRQGLSGGGGSL
ASGGPGPGHASLSQRLRLYLADSWNQCDLVALTCFLLGVGCRLTPGLYHLGRTVLCIDFM
VFTVRLLHIFTVNKQLGPKIVIVSKMMKDVFFFLFFLGVWLVAYGVATEGLLRPRDSDFP
SILRRVFYRPYLQIFGQIPQEDMDVALMEHSNCSSEPGFWAHPPGAQAGTCVSQYANWLV
VLLLVIFLLVANILLVNLLIAMFSYTFGKVQGNSDLYWKAQRYRLIREFHSRPALAPPFI
VISHLRLLLRQLCRRPRSPQPSSPALEHFRVYLSKEAERKLLTWESVHKENFLLARARDK
RESDSERLKRTSQKVDLALKQLGHIREYEQRLKVLEREVQQCSRVLGWVAEALSRSALLP
PGGPPPPDLPGSKD
Target Type
Clinical trial
Target Bioclass
Transporter and channel
Family
Transient receptor (TC 1.A.4) family, LTrpC subfamily, TRPM4 sub-subfamily
Subcellular location
Cell membrane
Function
Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Plays a role in keratinocyte differentiation.
TTD ID
T94255
Uniprot ID
Q8TD43
DrugMap ID
TTJ2HKA
Ensemble ID
ENST00000252826.10
HGNC ID
HGNC:17993
ChEMBL ID
CHEMBL1628469

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CALU1 SNV: p.E1142K .
CCK81 SNV: p.A145T DBIA    Probe Info 
FTC133 SNV: p.G886S .
HCT15 SNV: p.G82E; p.L1075M .
HKGZCC SNV: p.K1129E DBIA    Probe Info 
J82 SNV: p.L511Q .
KYSE410 SNV: p.T155N DBIA    Probe Info 
L428 Deletion: p.P115TfsTer162
SNV: p.A114V		 .
MELHO SNV: p.P1204Q .
MFE296 SNV: p.L225M .
MOLT4 SNV: p.R1184H .
NCIH1048 Deletion: p.R41GfsTer18 .
NCIH2286 SNV: p.R601P .
NCIH716 SNV: p.F975I .
SKNSH SNV: p.P1201Q .
SW620 SNV: p.D1055N .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C630(1.28)  LDD0593  [1]
ATP probe
 Probe Info  		N.A.  LDD0199  [2]
IA-alkyne
 Probe Info  		N.A.  LDD0162  [3]
TFBX
 Probe Info  		N.A.  LDD0148  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0276  AC17 HCT 116 C630(1.28)  LDD0593  [1]
 LDCM0277  AC18 HCT 116 C630(0.85)  LDD0594  [1]
 LDCM0278  AC19 HCT 116 C630(0.93)  LDD0595  [1]
 LDCM0280  AC20 HCT 116 C630(0.92)  LDD0597  [1]
 LDCM0281  AC21 HCT 116 C630(1.01)  LDD0598  [1]
 LDCM0282  AC22 HCT 116 C630(1.23)  LDD0599  [1]
 LDCM0283  AC23 HCT 116 C630(1.07)  LDD0600  [1]
 LDCM0284  AC24 HCT 116 C630(1.04)  LDD0601  [1]
 LDCM0296  AC35 HCT 116 C630(1.06)  LDD0613  [1]
 LDCM0297  AC36 HCT 116 C630(1.06)  LDD0614  [1]
 LDCM0298  AC37 HCT 116 C630(1.11)  LDD0615  [1]
 LDCM0299  AC38 HCT 116 C630(1.16)  LDD0616  [1]
 LDCM0300  AC39 HCT 116 C630(1.05)  LDD0617  [1]
 LDCM0302  AC40 HCT 116 C630(1.07)  LDD0619  [1]
 LDCM0303  AC41 HCT 116 C630(1.04)  LDD0620  [1]
 LDCM0304  AC42 HCT 116 C630(1.03)  LDD0621  [1]
 LDCM0305  AC43 HCT 116 C630(1.03)  LDD0622  [1]
 LDCM0306  AC44 HCT 116 C630(1.04)  LDD0623  [1]
 LDCM0307  AC45 HCT 116 C630(0.97)  LDD0624  [1]
 LDCM0320  AC57 HCT 116 C630(1.02); C758(1.09); C759(1.09)  LDD0637  [1]
 LDCM0321  AC58 HCT 116 C758(0.85); C759(0.85); C630(0.92)  LDD0638  [1]
 LDCM0322  AC59 HCT 116 C630(1.12); C758(1.20); C759(1.20)  LDD0639  [1]
 LDCM0324  AC60 HCT 116 C630(1.07); C758(1.46); C759(1.46)  LDD0641  [1]
 LDCM0325  AC61 HCT 116 C630(0.97); C758(1.29); C759(1.29)  LDD0642  [1]
 LDCM0326  AC62 HCT 116 C630(0.98); C758(1.51); C759(1.51)  LDD0643  [1]
 LDCM0327  AC63 HCT 116 C630(0.98); C758(1.05); C759(1.05)  LDD0644  [1]
 LDCM0328  AC64 HCT 116 C630(0.96); C758(1.22); C759(1.22)  LDD0645  [1]
 LDCM0329  AC65 HCT 116 C758(1.06); C759(1.06); C630(1.34)  LDD0646  [1]
 LDCM0330  AC66 HCT 116 C630(1.14); C758(1.27); C759(1.27)  LDD0647  [1]
 LDCM0331  AC67 HCT 116 C630(0.92); C758(1.28); C759(1.28)  LDD0648  [1]
 LDCM0332  AC68 HCT 116 C630(0.89)  LDD0649  [1]
 LDCM0333  AC69 HCT 116 C630(0.69)  LDD0650  [1]
 LDCM0335  AC70 HCT 116 C630(0.80)  LDD0652  [1]
 LDCM0336  AC71 HCT 116 C630(0.96)  LDD0653  [1]
 LDCM0337  AC72 HCT 116 C630(0.85)  LDD0654  [1]
 LDCM0338  AC73 HCT 116 C630(0.96)  LDD0655  [1]
 LDCM0339  AC74 HCT 116 C630(0.88)  LDD0656  [1]
 LDCM0340  AC75 HCT 116 C630(0.84)  LDD0657  [1]
 LDCM0341  AC76 HCT 116 C630(0.96)  LDD0658  [1]
 LDCM0342  AC77 HCT 116 C630(1.10)  LDD0659  [1]
 LDCM0343  AC78 HCT 116 C630(0.77)  LDD0660  [1]
 LDCM0344  AC79 HCT 116 C630(1.06)  LDD0661  [1]
 LDCM0346  AC80 HCT 116 C630(0.86)  LDD0663  [1]
 LDCM0347  AC81 HCT 116 C630(0.40)  LDD0664  [1]
 LDCM0348  AC82 HCT 116 C630(0.85)  LDD0665  [1]
 LDCM0367  CL1 HCT 116 C630(0.95)  LDD0684  [1]
 LDCM0368  CL10 HCT 116 C630(0.87)  LDD0685  [1]
 LDCM0374  CL105 HCT 116 C630(0.89)  LDD0691  [1]
 LDCM0375  CL106 HCT 116 C630(0.74)  LDD0692  [1]
 LDCM0376  CL107 HCT 116 C630(1.08)  LDD0693  [1]
 LDCM0377  CL108 HCT 116 C630(0.98)  LDD0694  [1]
 LDCM0378  CL109 HCT 116 C630(0.90)  LDD0695  [1]
 LDCM0379  CL11 HCT 116 C630(0.88)  LDD0696  [1]
 LDCM0380  CL110 HCT 116 C630(0.93)  LDD0697  [1]
 LDCM0381  CL111 HCT 116 C630(0.96)  LDD0698  [1]
 LDCM0387  CL117 HCT 116 C630(0.90)  LDD0704  [1]
 LDCM0388  CL118 HCT 116 C630(0.97)  LDD0705  [1]
 LDCM0389  CL119 HCT 116 C630(0.88)  LDD0706  [1]
 LDCM0390  CL12 HCT 116 C630(1.14)  LDD0707  [1]
 LDCM0391  CL120 HCT 116 C630(1.12)  LDD0708  [1]
 LDCM0396  CL125 HCT 116 C630(1.19); C758(1.53); C759(1.53)  LDD0713  [1]
 LDCM0397  CL126 HCT 116 C758(1.10); C759(1.10); C630(1.15)  LDD0714  [1]
 LDCM0398  CL127 HCT 116 C758(0.77); C759(0.77); C630(1.37)  LDD0715  [1]
 LDCM0399  CL128 HCT 116 C630(1.03); C758(1.22); C759(1.22)  LDD0716  [1]
 LDCM0400  CL13 HCT 116 C630(0.99)  LDD0717  [1]
 LDCM0401  CL14 HCT 116 C630(1.16)  LDD0718  [1]
 LDCM0402  CL15 HCT 116 C630(0.95)  LDD0719  [1]
 LDCM0403  CL16 HCT 116 C630(0.74); C758(0.97); C759(0.97)  LDD0720  [1]
 LDCM0404  CL17 HCT 116 C758(0.52); C759(0.52); C630(0.69)  LDD0721  [1]
 LDCM0405  CL18 HCT 116 C630(0.54); C758(0.80); C759(0.80)  LDD0722  [1]
 LDCM0406  CL19 HCT 116 C630(0.59); C758(0.82); C759(0.82)  LDD0723  [1]
 LDCM0407  CL2 HCT 116 C630(1.19)  LDD0724  [1]
 LDCM0408  CL20 HCT 116 C630(0.63); C758(1.01); C759(1.01)  LDD0725  [1]
 LDCM0409  CL21 HCT 116 C630(0.59); C758(0.87); C759(0.87)  LDD0726  [1]
 LDCM0410  CL22 HCT 116 C630(0.68); C758(0.99); C759(0.99)  LDD0727  [1]
 LDCM0411  CL23 HCT 116 C630(0.75); C758(1.03); C759(1.03)  LDD0728  [1]
 LDCM0412  CL24 HCT 116 C630(0.67); C758(0.64); C759(0.64)  LDD0729  [1]
 LDCM0413  CL25 HCT 116 C630(0.68); C758(0.60); C759(0.60)  LDD0730  [1]
 LDCM0414  CL26 HCT 116 C630(0.68); C758(0.67); C759(0.67)  LDD0731  [1]
 LDCM0415  CL27 HCT 116 C630(0.74); C758(0.66); C759(0.66)  LDD0732  [1]
 LDCM0416  CL28 HCT 116 C630(0.60); C758(0.74); C759(0.74)  LDD0733  [1]
 LDCM0417  CL29 HCT 116 C630(0.77); C758(0.93); C759(0.93)  LDD0734  [1]
 LDCM0418  CL3 HCT 116 C630(1.10)  LDD0735  [1]
 LDCM0419  CL30 HCT 116 C630(0.66); C758(0.84); C759(0.84)  LDD0736  [1]
 LDCM0429  CL4 HCT 116 C630(1.02)  LDD0746  [1]
 LDCM0436  CL46 HCT 116 C630(1.49); C758(0.79); C759(0.79)  LDD0753  [1]
 LDCM0437  CL47 HCT 116 C630(1.08); C758(0.73); C759(0.73)  LDD0754  [1]
 LDCM0438  CL48 HCT 116 C630(1.60); C758(1.15); C759(1.15)  LDD0755  [1]
 LDCM0439  CL49 HCT 116 C630(1.22); C758(0.81); C759(0.81)  LDD0756  [1]
 LDCM0440  CL5 HCT 116 C630(1.18)  LDD0757  [1]
 LDCM0441  CL50 HCT 116 C630(1.25); C758(0.91); C759(0.91)  LDD0758  [1]
 LDCM0442  CL51 HCT 116 C630(1.52); C758(0.82); C759(0.82)  LDD0759  [1]
 LDCM0443  CL52 HCT 116 C630(1.26); C758(0.91); C759(0.91)  LDD0760  [1]
 LDCM0444  CL53 HCT 116 C630(1.05); C758(1.01); C759(1.01)  LDD0761  [1]
 LDCM0445  CL54 HCT 116 C630(1.00); C758(1.24); C759(1.24)  LDD0762  [1]
 LDCM0446  CL55 HCT 116 C630(1.22); C758(0.84); C759(0.84)  LDD0763  [1]
 LDCM0447  CL56 HCT 116 C630(1.10); C758(0.98); C759(0.98)  LDD0764  [1]
 LDCM0448  CL57 HCT 116 C630(1.54); C758(0.65); C759(0.65)  LDD0765  [1]
 LDCM0449  CL58 HCT 116 C630(1.19); C758(1.19); C759(1.19)  LDD0766  [1]
 LDCM0450  CL59 HCT 116 C630(1.17); C758(0.88); C759(0.88)  LDD0767  [1]
 LDCM0451  CL6 HCT 116 C630(0.94)  LDD0768  [1]
 LDCM0452  CL60 HCT 116 C630(1.17); C758(1.15); C759(1.15)  LDD0769  [1]
 LDCM0453  CL61 HCT 116 C758(1.09); C759(1.09)  LDD0770  [1]
 LDCM0454  CL62 HCT 116 C758(1.89); C759(1.89)  LDD0771  [1]
 LDCM0455  CL63 HCT 116 C758(1.57); C759(1.57)  LDD0772  [1]
 LDCM0456  CL64 HCT 116 C758(0.95); C759(0.95)  LDD0773  [1]
 LDCM0457  CL65 HCT 116 C758(1.48); C759(1.48)  LDD0774  [1]
 LDCM0458  CL66 HCT 116 C758(1.07); C759(1.07)  LDD0775  [1]
 LDCM0459  CL67 HCT 116 C758(1.36); C759(1.36)  LDD0776  [1]
 LDCM0460  CL68 HCT 116 C758(1.05); C759(1.05)  LDD0777  [1]
 LDCM0461  CL69 HCT 116 C758(1.37); C759(1.37)  LDD0778  [1]
 LDCM0462  CL7 HCT 116 C630(1.22)  LDD0779  [1]
 LDCM0463  CL70 HCT 116 C758(1.39); C759(1.39)  LDD0780  [1]
 LDCM0464  CL71 HCT 116 C758(2.01); C759(2.01)  LDD0781  [1]
 LDCM0465  CL72 HCT 116 C758(1.32); C759(1.32)  LDD0782  [1]
 LDCM0466  CL73 HCT 116 C758(1.21); C759(1.21)  LDD0783  [1]
 LDCM0467  CL74 HCT 116 C758(1.18); C759(1.18)  LDD0784  [1]
 LDCM0469  CL76 HCT 116 C758(1.23); C759(1.23)  LDD0786  [1]
 LDCM0470  CL77 HCT 116 C758(0.75); C759(0.75)  LDD0787  [1]
 LDCM0471  CL78 HCT 116 C758(1.07); C759(1.07)  LDD0788  [1]
 LDCM0472  CL79 HCT 116 C758(0.72); C759(0.72)  LDD0789  [1]
 LDCM0473  CL8 HCT 116 C630(0.88)  LDD0790  [1]
 LDCM0474  CL80 HCT 116 C758(0.93); C759(0.93)  LDD0791  [1]
 LDCM0475  CL81 HCT 116 C758(0.68); C759(0.68)  LDD0792  [1]
 LDCM0476  CL82 HCT 116 C758(0.97); C759(0.97)  LDD0793  [1]
 LDCM0477  CL83 HCT 116 C758(1.01); C759(1.01)  LDD0794  [1]
 LDCM0478  CL84 HCT 116 C758(1.09); C759(1.09)  LDD0795  [1]
 LDCM0479  CL85 HCT 116 C758(1.05); C759(1.05)  LDD0796  [1]
 LDCM0480  CL86 HCT 116 C758(0.84); C759(0.84)  LDD0797  [1]
 LDCM0481  CL87 HCT 116 C758(0.86); C759(0.86)  LDD0798  [1]
 LDCM0482  CL88 HCT 116 C758(0.77); C759(0.77)  LDD0799  [1]
 LDCM0483  CL89 HCT 116 C758(1.12); C759(1.12)  LDD0800  [1]
 LDCM0484  CL9 HCT 116 C630(1.05)  LDD0801  [1]
 LDCM0485  CL90 HCT 116 C758(2.31); C759(2.31)  LDD0802  [1]
 LDCM0468  Fragment33 HCT 116 C758(1.08); C759(1.08)  LDD0785  [1]
 LDCM0022  KB02 22RV1 C385(1.35)  LDD2243  [5]
 LDCM0023  KB03 22RV1 C385(1.97)  LDD2660  [5]
 LDCM0024  KB05 COLO792 C1182(1.92)  LDD3310  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein S100-A10 (S100A10) S-100 family P60903
Other
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein S100-A11 (S100A11) S-100 family P31949
Protein S100-A2 (S100A2) S-100 family P29034
Protein S100-A3 (S100A3) S-100 family P33764
Protein S100-A4 (S100A4) S-100 family P26447
Protein S100-A5 (S100A5) S-100 family P33763
Protein S100-A6 (S100A6) S-100 family P06703
Protein S100-A8 (S100A8) S-100 family P05109

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Glyburide Small molecular drug DB01016
Investigative
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
9-phenanthrol Small molecular drug D0G2MU
Adenosine Diphosphate Small molecular drug D05NWF
Amp-pnp Small molecular drug D00ICA
Btp2 Small molecular drug D0JV2P
Decavanadate Small molecular drug D06KHR
Pip2 Small molecular drug D07ZAJ

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 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
5 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