NALCN
entrez
259232
canonical
uniprot
Q8IZF0
canonical
ensembl
ENSG00000102452
resolver
ensp
ENSP00000251127
resolver
ensp
ENSP00000501603
resolver
ensp
ENSP00000501955
resolver
ensp
ENSP00000528774
resolver
enst
ENST00000675332
resolver
enst
ENST00000676315
resolver
genesymbol
NALCN
resolver
genesymbol_syn
VGCNL1
resolver
hgnc
HGNC:19082
resolver
uniprot
A0A6Q8PF19
resolver
uniprot
A0A6Q8PFS9
resolver
uniprot
Q6P2S6
resolver
uniprot
Q6ZMI7
resolver
uniprot
Q8IZZ1
resolver
uniprot
Q8TAH1
resolver
uniprot_entry
A0A6Q8PF19_HUMAN
resolver
uniprot_entry
A0A6Q8PFS9_HUMAN
resolver
uniprot_entry
NALCN_HUMAN
resolver
uniprot_sec
Q6P2S6
resolver
uniprot_sec
Q6ZMI7
resolver
uniprot_sec
Q8IZZ1
resolver
uniprot_sec
Q8TAH1
resolver
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:0000269|PubMed:32494638, ECO:0000269|PubMed:33203861}.
uniprot
proteins
amino_acid_sequence
MLKRKQSSRVEAQPVTDFGPDESLSDNADILWINKPWVHSLLRICAIISVISVCMNTPMTFEHYPPLQYVTFTLDTLLMFLYTAEMIAKMHIRGIVKGDSSYVKDRWCVFDGFMVFCLWVSLVLQVFEIADIVDQMSPWGMLRIPRPLIMIRAFRIYFRFELPRTRITNILKRSGEQIWSVSIFLLFFLLLYGILGVQMFGTFTYHCVVNDTKPGNVTWNSLAIPDTHCSPELEEGYQCPPGFKCMDLEDLGLSRQELGYSGFNEIGTSIFTVYEAASQEGWVFLMYRAIDSFPRWRSYFYFITLIFFLAWLVKNVFIAVIIETFAEIRVQFQQMWGSRSSTTSTATTQMFHEDAAGGWQLVAVDVNKPQGRAPACLQKMMRSSVFHMFILSMVTVDVIVAASNYYKGENFRRQYDEFYLAEVAFTVLFDLEALLKIWCLGFTGYISSSLHKFELLLVIGTTLHVYPDLYHSQFTYFQVLRVVRLIKISPALEDFVYKIFGPGKKLGSLVVFTASLLIVMSAISLQMFCFVEELDRFTTFPRAFMSMFQILTQEGWVDVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRESFMKQFIDRQQQDTCCLLRSLPTTSSSSCDHSKRSAIEDNKYIDQKLRKSVFSIRARNLLEKETAVTKILRACTRQRMLSGSFEGQPAKERSILSVQHHIRQERRSLRHGSNSQRISRGKSLETLTQDHSNTVRYRNAQREDSEIKMIQEKKEQAEMKRKVQEEELRENHPYFDKPLFIVGREHRFRNFCRVVVRARFNASKTDPVTGAVKNTKYHQLYDLLGLVTYLDWVMIIVTICSCISMMFESPFRRVMHAPTLQIAEYVFVIFMSIELNLKIMADGLFFTPTAVIRDFGGVMDIFIYLVSLIFLCWMPQNVPAESGAQLLMVLRCLRPLRIFKLVPQMRKVVRELFSGFKEIFLVSILLLTLMLVFASFGVQLFAGKLAKCNDPNIIRREDCNGIFRINVSVSKNLNLKLRPGEKKPGFWVPRVWANPRNFNFDNVGNAMLALFEVLSLKGWVEVRDVIIHRVGPIHGIYIHVFVFLGCMIGLTLFVGVVIANFNENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRAKMYDITQHPFFKRTIALLVLAQSVLLSVKWDVEDPVTVPLATMSVVFTFIFVLEVTMKIIAMSPAGFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVIVFRFFSICGKHVTLKMLLLTVVVSMYKSFFIIVGMFLLLLCYAFAGVVLFGTVKYGENINRHANFSSAGKAITVLFRIVTGEDWNKIMHDCMVQPPFCTPDEFTYWATDCGNYAGALMYFCSFYVIIAYIMLNLLVAIIVENFSLFYSTEEDQLLSYNDLRHFQIIWNMVDDKREGVIPTFRVKFLLRLLRGRLEVDLDKDKLLFKHMCYEMERLHNGGDVTFHDVLSMLSYRSVDIRKSLQLEELLAREQLEYTIEEEVAKQTIRMWLKKCLKRIRAKQQQSCSIIHSLRESQQQELSRFLNPPSIETTQPSEDTNANSQDNSMQPETSSQQQLLSPTLSDRGGSRQDAADAGKPQRKFGQWRLPSAPKPISHSVSSVNLRFGGRTTMKSVVCKMNPMTDAASCGSEVKKWWTRQLTVESDESGDDLLDI
uniprot
proteins
disease_involvement
DISEASE: Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (IHPRF1) [MIM:615419]: A neurodegenerative disease characterized by variable degrees of hypotonia, speech impairment, intellectual disability, pyramidal signs, subtle facial dysmorphism, and chronic constipation. Some patients manifest neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid bodies in tissue biopsies. {ECO:0000269|PubMed:23749988, ECO:0000269|PubMed:24075186, ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32698188}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) [MIM:616266]: A disease characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, abnormal tone, most commonly manifested as hypotonia, and variable degrees of developmental delay. {ECO:0000269|PubMed:25683120, ECO:0000269|PubMed:25864427, ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32698188}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:17448995, PubMed:32494638, PubMed:33203861, PubMed:35387979, PubMed:34929720). The NALCN channelosome complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (PubMed:17448995, PubMed:31409833, PubMed:35387979, PubMed:34929720). The NALCN channelosome is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations (PubMed:32494638). 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). The NALCN channelosome 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:0000269|PubMed:17448995, ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32494638, ECO:0000269|PubMed:33203861, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979}.
uniprot
proteins
mass_dalton
200331
uniprot
proteins
mutagenesis
MUTAGEN 146; /note="R->Q: Affects voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 152; /note="R->Q: Affects voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 155; /note="R->Q: Affects voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 280; /note="E->A: Drastically more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 325; /note="F->A: Increases channel activity."; /evidence="ECO:0000269|PubMed:33203861"; MUTAGEN 328; /note="I->W: Increases channel activity."; /evidence="ECO:0000269|PubMed:33203861"; MUTAGEN 332; /note="F->A: No effect on the channel activity."; /evidence="ECO:0000269|PubMed:33203861"; MUTAGEN 481; /note="R->Q: Exhibits altered current kinetics."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 484; /note="R->Q: Does not exhibited altered current kinetics."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 487; /note="K->Q: Does not exhibited altered current kinetics."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 504; /note="K->D,A: Decreases channel activity."; /evidence="ECO:0000269|PubMed:33203861"; MUTAGEN 505; /note="K->A: Decreases channel activity."; /evidence="ECO:0000269|PubMed:33203861"; MUTAGEN 554; /note="E->A: Drastically more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 558; /note="D->A: Moderately more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 561; /note="D->A: No effect on the blockage of NALCN pore by Ca(2+)."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 989; /note="R->Q: Does not affect the voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 992; /note="R->Q: Does not affect the voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 995; /note="R->Q: Does not affect the voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 1115; /note="K->A: No effect on the blockage of NALCN pore by Ca(2+)."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 1119; /note="E->A: Moderately more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 1310; /note="R->Q: Does not affect the voltage sensitivity."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 1389; /note="E->A: Moderately more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638"; MUTAGEN 1390; /note="D->A: Drastically more sensitive to Ca(2+) block."; /evidence="ECO:0000269|PubMed:32494638
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues (By similarity). {ECO:0000250|UniProtKB:Q8BXR5}.
uniprot
proteins
protein_family
NALCN family
uniprot
proteins
pubmed
12364586
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057823
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17448995
uniprot
proteins
pubmed
23749988
uniprot
proteins
pubmed
24075186
uniprot
proteins
pubmed
25683120
uniprot
proteins
pubmed
25864427
uniprot
proteins
pubmed
26763878
uniprot
proteins
pubmed
27214504
uniprot
proteins
pubmed
31409833
uniprot
proteins
pubmed
32494638
uniprot
proteins
pubmed
32698188
uniprot
proteins
pubmed
33203861
uniprot
proteins
pubmed
34929720
uniprot
proteins
pubmed
35387979
uniprot
proteins
sequence_length
1738
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32494638, ECO:0000269|PubMed:32698188}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 37..57; /note="Helical; Name=S1 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 66..90; /note="Helical; Name=S2 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 107..129; /note="Helical; Name=S3 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 138..158; /note="Helical; Voltage-sensor; Name=S4 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 174..199; /note="Helical; Name=S5 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 295..322; /note="Helical; Name=S6 of VSD1"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 383..403; /note="Helical; Name=S1 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 417..439; /note="Helical; Name=S2 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 448..468; /note="Helical; Name=S3 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 473..492; /note="Helical; Voltage-sensor; Name=S4 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 503..530; /note="Helical; Name=S5 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 570..599; /note="Helical; Name=S6 of VSD2"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 887..906; /note="Helical; Name=S1 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 916..939; /note="Helical; Name=S2 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 948..972; /note="Helical; Name=S3 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 981..1003; /note="Helical; Voltage-sensor; Name=S4 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1016..1039; /note="Helical; Name=S5 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1130..1159; /note="Helical; Name=S6 of VSD3"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1211..1227; /note="Helical; Name=S1 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1237..1260; /note="Helical; Name=S2 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1272..1293; /note="Helical; Name=S3 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1297..1318; /note="Helical; Voltage-sensor; Name=S4 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1332..1357; /note="Helical; Name=S5 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI"; TRANSMEM 1421..1447; /note="Helical; Name=S6 of VSD4"; /evidence="ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:34929720, ECO:0000269|PubMed:35387979, ECO:0007744|PDB:6XIW, ECO:0007744|PDB:7SX3, ECO:0007744|PDB:7SX4, ECO:0007744|PDB:7WJI
uniprot
proteins