Details of the Target

General Information of Target

Target ID LDTP08697
Target Name Sodium leak channel NALCN (NALCN)
Gene Name NALCN
Gene ID 259232
Synonyms
VGCNL1; Sodium leak channel NALCN; CanIon; Sodium leak channel non-selective protein; Voltage gated channel-like protein 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLKRKQSSRVEAQPVTDFGPDESLSDNADILWINKPWVHSLLRICAIISVISVCMNTPMT
FEHYPPLQYVTFTLDTLLMFLYTAEMIAKMHIRGIVKGDSSYVKDRWCVFDGFMVFCLWV
SLVLQVFEIADIVDQMSPWGMLRIPRPLIMIRAFRIYFRFELPRTRITNILKRSGEQIWS
VSIFLLFFLLLYGILGVQMFGTFTYHCVVNDTKPGNVTWNSLAIPDTHCSPELEEGYQCP
PGFKCMDLEDLGLSRQELGYSGFNEIGTSIFTVYEAASQEGWVFLMYRAIDSFPRWRSYF
YFITLIFFLAWLVKNVFIAVIIETFAEIRVQFQQMWGSRSSTTSTATTQMFHEDAAGGWQ
LVAVDVNKPQGRAPACLQKMMRSSVFHMFILSMVTVDVIVAASNYYKGENFRRQYDEFYL
AEVAFTVLFDLEALLKIWCLGFTGYISSSLHKFELLLVIGTTLHVYPDLYHSQFTYFQVL
RVVRLIKISPALEDFVYKIFGPGKKLGSLVVFTASLLIVMSAISLQMFCFVEELDRFTTF
PRAFMSMFQILTQEGWVDVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVILD
NLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRE
SFMKQFIDRQQQDTCCLLRSLPTTSSSSCDHSKRSAIEDNKYIDQKLRKSVFSIRARNLL
EKETAVTKILRACTRQRMLSGSFEGQPAKERSILSVQHHIRQERRSLRHGSNSQRISRGK
SLETLTQDHSNTVRYRNAQREDSEIKMIQEKKEQAEMKRKVQEEELRENHPYFDKPLFIV
GREHRFRNFCRVVVRARFNASKTDPVTGAVKNTKYHQLYDLLGLVTYLDWVMIIVTICSC
ISMMFESPFRRVMHAPTLQIAEYVFVIFMSIELNLKIMADGLFFTPTAVIRDFGGVMDIF
IYLVSLIFLCWMPQNVPAESGAQLLMVLRCLRPLRIFKLVPQMRKVVRELFSGFKEIFLV
SILLLTLMLVFASFGVQLFAGKLAKCNDPNIIRREDCNGIFRINVSVSKNLNLKLRPGEK
KPGFWVPRVWANPRNFNFDNVGNAMLALFEVLSLKGWVEVRDVIIHRVGPIHGIYIHVFV
FLGCMIGLTLFVGVVIANFNENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFR
AKMYDITQHPFFKRTIALLVLAQSVLLSVKWDVEDPVTVPLATMSVVFTFIFVLEVTMKI
IAMSPAGFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVIVFRFFSICGKHVT
LKMLLLTVVVSMYKSFFIIVGMFLLLLCYAFAGVVLFGTVKYGENINRHANFSSAGKAIT
VLFRIVTGEDWNKIMHDCMVQPPFCTPDEFTYWATDCGNYAGALMYFCSFYVIIAYIMLN
LLVAIIVENFSLFYSTEEDQLLSYNDLRHFQIIWNMVDDKREGVIPTFRVKFLLRLLRGR
LEVDLDKDKLLFKHMCYEMERLHNGGDVTFHDVLSMLSYRSVDIRKSLQLEELLAREQLE
YTIEEEVAKQTIRMWLKKCLKRIRAKQQQSCSIIHSLRESQQQELSRFLNPPSIETTQPS
EDTNANSQDNSMQPETSSQQQLLSPTLSDRGGSRQDAADAGKPQRKFGQWRLPSAPKPIS
HSVSSVNLRFGGRTTMKSVVCKMNPMTDAASCGSEVKKWWTRQLTVESDESGDDLLDI
Target Bioclass
Transporter and channel
Family
NALCN family
Subcellular location
Cell membrane
Function
Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability. NALCN channel functions as a multi-protein complex, which consists at least of NALCN, NALF1, UNC79 and UNC80. NALCN is the voltage-sensing, pore-forming subunit of the NALCN channel complex. NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. In addition to its role in regulating neuronal excitability, is required for normal respiratory rhythm, systemic osmoregulation by controlling the serum sodium concentration and in the regulation of the intestinal pace-making activity in the interstitial cells of Cajal. NALCN channel is also activated by neuropeptides such as neurotensin and substance P (SP) through a SRC family kinases-dependent pathway. In addition, NALCN activity is enhanced/modulated by several GPCRs, such as CHRM3.
Uniprot ID
Q8IZF0
Ensemble ID
ENST00000251127.11
HGNC ID
HGNC:19082

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
786O SNV: p.L918F .
CAL33 SNV: p.M663L .
CAL51 SNV: p.Y301C; p.S1638N .
CASKI SNV: p.W1175Ter .
CCK81 SNV: p.L248P; p.A1166V .
CHL1 SNV: p.S1698Y .
DU145 SNV: p.M957I .
HCC1143 SNV: p.M1476I .
HCT116 SNV: p.D1659E .
HCT15 Deletion: p.L1019WfsTer7 .
HEC1B SNV: p.Y274H .
HT115 SNV: p.A363V .
IGR1 SNV: p.G1483R .
JHH4 SNV: p.R694S .
KARPAS299 Substitution: p.P1191T .
KARPAS422 SNV: p.K1662N .
LS180 SNV: p.M55T; p.T552A .
NCIH1299 SNV: p.W179L .
NCIH146 SNV: p.A1375T .
NCIH2286 SNV: p.D21N .
NCIH23 SNV: p.W571C .
NCIH446 Substitution: p.Q757E .
NCIN87 SNV: p.M150R .
NUGC3 Deletion: p.F1151LfsTer4
SNV: p.E1564Ter		 .
OCUG1 SNV: p.H1189N .
SNU449 SNV: p.W119Ter .
SW1783 SNV: p.V458I .
SW1990 SNV: p.L1010P .
T24 SNV: p.R1053I .
U937 SNV: p.P946L .
WM793 SNV: p.E825K; p.Q1002R .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Acrolein
 Probe Info  		N.A.  LDD0231  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0109  NEM HeLa N.A.  LDD0231  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein MOX-2 (MEOX2) . P50222
GPCR
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Muscarinic acetylcholine receptor M3 (CHRM3) G-protein coupled receptor 1 family P20309

References

1 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.