Q6Q760
uniprot
Q6Q760
canonical
activity_regulation
ACTIVITY REGULATION: Inhibited by low micromolar concentrations of Gd(3+) and high micromolar concentrations of verapamil. Insensitive to tetrodotoxin (TTX) and potentiated by low external Ca(2+) concentration. {ECO:0000250|UniProtKB:Q8IZF0}.
uniprot
proteins
amino_acid_sequence
MLKRKQSSRVEAQPVTDFGPDESLSDNADILWINKPWVHSLLRICAIISVIPVCMNTPMTFEHYPPLQYVTFTLDTLLMFLYTAEMIAKMHIRGIVKGDSSYVKDRWCVFDGFMVFCLWVSLVLQVFEIADIVDQMSPWGMLRIPRPLIMIRAFRIYFRFELPRTRITNILKRSGEQIWSVSIFLLFFLLLYGILGVQMFGTFTYHCVVNDTKPGNVTWNSLAIPDTHCSPELEEGYQCPPGFKCMDLEDLGLSRQELGYSGFNEIGTSIFTVYEASSQEGWVFLMYRAIDSFPRWRSYFYFITLIFFLAWLVKNVFIAVIIETFAEIRVQFQQMWGTRSSTTSTATTQMFHEDAAGGWQLVAVDVNKPQGRAPACLQKMMRSSVFHMFILSMVTVDVIVAASNYYKGENFRRQYDEFYLAEVAFTVLFDLEALLKIWCLGFTGYISSSLHKFELLLVIGTTLHVYPDLYHSQFTYFQVLRVVRLIKISPALEDFVYKIFGPGKKLGSLVVFTASLLIVMSAISLQMFCFVEELDRFTTFPRAFMSMFQILTQEGWVDVMDQTLNAVGHMWAPLVAIYFILYHLFATLILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRESFMKQFIDRQQQDTCCLFRILPSTSSSSCDNPKRPTVEDNKYIDQKLRKSVFSIRARNLLEKETAVTKILRACTRQRMLSGSFEGQPTKERSILSVQHHIRQERRSLRHGSNSQRISRGKSLETLTQDHSNTVRYRNAQREDSEIKMIQEKKEQAEMKRKVQEEELRENHPYFDKPLFIVGREHRFRNFCRVVVRARFNASKTDPVTGAVKNTKYHQLYDLLGLVTYLDWVMITVTICSCISMMFESPFRRVMHAPTLQIAEYVFVIFMSIELNLKIMADGLFFTPTAVIRDFGGVMDIFIYLVSLIFLCWMPQNVPAESGAQLLMVLRCLRPLRIFKLVPQMRKVVRELFSGFKEIFLVSILLLTLMLVFASFGVQLFAGKLAKCNDPNIIRREDCNGIFRINVSVSKNLNLKLRPGEKKPGFWVPRVWANPRNFNFDNVGNAMLALFEVLSLKGWVEVRDVIIHRVGPIHGIYIHVFVFLGCMIGLTLFVGVVIANFNENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRAKMYDITQHPFFKRTIALLVLAQSVLLSVKWDVEDPVTVPLATMSVVFTFIFVLEVTMKIIAMSPAGFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVIVFRFFSICGKHVTLKMLLLTVVVSMYKSFFIIVGMFLLLLCYAFAGVVLFGTVKYGENINRHANFSSAGKAITVLFRIVTGEDWNKIMHDCMVQPPFCTPDEFTYWATDCGNYAGALMYFCSFYVIIAYIMLNLLVAIIVENFSLFYSTEEDQLLSYNDLRHFQIIWNMVDDKREGVIPTFRVKFLLRLLRGRLEVDLDKDKLLFKHMCYEMERLHNGGDVTFHDVLSMLSYRSVDIRKSLQLEELLAREQLEYTIEEEVAKQTIRMWLKKCLKRIRAKQQQSCSIIHSLRESQQQELSRFLNPPSIETTQPSEDTNANSQDHNTQPESSSQQQLLSPTLSDRGGSRQDAADTGKPQRKIGQWRLPSAPKPISHSVSSVNLRFGGRTTMKSVVCKMNPMPDTASCGSEVKKWWTRQLTVESDESGDDLLDI
uniprot
proteins
function
FUNCTION: Voltage-sensing, pore-forming subunit of the NALCN channelosome complex, which regulates the resting membrane potential by depolarizing sodium leak currents (By similarity). The NALCN channelosome complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (By similarity). The NALCN channelosome is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations (By similarity). 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 (By similarity). Plays a critical role in both maintenance of spontaneous firing of substantia nigra pars reticulata (SNr) neurons and physiological modulation of SNr neuron excitability (By similarity). NALCN channel is also activated by neuropeptides such as neurotensin and substance P (SP) through a SRC family kinases-dependent pathway (By similarity). In addition, NALCN activity is enhanced/modulated by several GPCRs, such as CHRM3 (By similarity). {ECO:0000250|UniProtKB:Q8BXR5, ECO:0000250|UniProtKB:Q8IZF0}.
uniprot
proteins
mass_dalton
200491
uniprot
proteins
mutagenesis
MUTAGEN 1389; /note="E->A: Affects ion selectivity."; /evidence="ECO:0000269|PubMed:33273469"; MUTAGEN 1390; /note="D->A: Affects ion selectivity."; /evidence="ECO:0000269|PubMed:33273469
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues. {ECO:0000250|UniProtKB:Q8BXR5}.
uniprot
proteins
protein_family
NALCN family
uniprot
proteins
pubmed
10094463
uniprot
proteins
pubmed
17448995
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
33273469
uniprot
proteins
sequence_length
1738
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8IZF0}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 37..57; /note="Helical; Name=S1 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 66..90; /note="Helical; Name=S2 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 107..129; /note="Helical; Name=S3 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 138..158; /note="Helical; Voltage-sensor; Name=S4 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 174..199; /note="Helical; Name=S5 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 295..322; /note="Helical; Name=S6 of VSD1"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 383..403; /note="Helical; Name=S1 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 417..439; /note="Helical; Name=S2 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 448..468; /note="Helical; Name=S3 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 473..492; /note="Helical; Voltage-sensor; Name=S4 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 503..530; /note="Helical; Name=S5 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 570..599; /note="Helical; Name=S6 of VSD2"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 887..906; /note="Helical; Name=S1 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 916..939; /note="Helical; Name=S2 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 948..972; /note="Helical; Name=S3 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 981..1003; /note="Helical; Voltage-sensor; Name=S4 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1016..1039; /note="Helical; Name=S5 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1130..1159; /note="Helical; Name=S6 of VSD3"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1211..1227; /note="Helical; Name=S1 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1237..1260; /note="Helical; Name=S2 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1272..1293; /note="Helical; Name=S3 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1297..1318; /note="Helical; Voltage-sensor; Name=S4 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1332..1357; /note="Helical; Name=S5 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0"; TRANSMEM 1421..1447; /note="Helical; Name=S6 of VSD4"; /evidence="ECO:0000250|UniProtKB:Q8IZF0
uniprot
proteins