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HighlightsThe sodium leak channel non-selective protein (NALCN) in humans is encoded by the NALCN gene. It belongs to the transmembrane cation channel superfamily and is a voltage-independent cation non-selective channel that is permeable to sodium, potassium and calcium ions. The channel is described as having two transmembrane helices on the flanks of the loop that determine the ion selectivity of the channels. Many eukaryotic channels have four additional transmembrane helices associated with voltage gating.
| Basic Information of NALCN | |
| Protein Name | Sodium leak channel non-selective protein |
| Gene Name | NALCN |
| Aliases | VGCNL1 |
| Organism | Homo sapiens (Human) |
| UniProt ID | Q8IZF0 |
| Transmembrane Times | 24 |
| Length (aa) | 1738 |
| Sequence | MLKRKQSSRVEAQPVTDFGPDESLSDNADILWINKPWVHSLLRICAIISVISVCMNTPMTFEHYPPLQYVTFTLDTLLMFLYTAEMIAKMHIRGIVKGDSSYVKDRWCVFDGFMVFCLWVSLVLQVFEIADIVDQMSPWGMLRIPRPLIMIRAFRIYFRFELPRTRITNILKRSGEQIWSVSIFLLFFLLLYGILGVQMFGTFTYHCVVNDTKPGNVTWNSLAIPDTHCSPELEEGYQCPPGFKCMDLEDLGLSRQELGYSGFNEIGTSIFTVYEAASQEGWVFLMYRAIDSFPRWRSYFYFITLIFFLAWLVKNVFIAVIIETFAEIRVQFQQMWGSRSSTTSTATTQMFHEDAAGGWQLVAVDVNKPQGRAPACLQKMMRSSVFHMFILSMVTVDVIVAASNYYKGENFRRQYDEFYLAEVAFTVLFDLEALLKIWCLGFTGYISSSLHKFELLLVIGTTLHVYPDLYHSQFTYFQVLRVVRLIKISPALEDFVYKIFGPGKKLGSLVVFTASLLIVMSAISLQMFCFVEELDRFTTFPRAFMSMFQILTQEGWVDVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRESFMKQFIDRQQQDTCCLLRSLPTTSSSSCDHSKRSAIEDNKYIDQKLRKSVFSIRARNLLEKETAVTKILRACTRQRMLSGSFEGQPAKERSILSVQHHIRQERRSLRHGSNSQRISRGKSLETLTQDHSNTVRYRNAQREDSEIKMIQEKKEQAEMKRKVQEEELRENHPYFDKPLFIVGREHRFRNFCRVVVRARFNASKTDPVTGAVKNTKYHQLYDLLGLVTYLDWVMIIVTICSCISMMFESPFRRVMHAPTLQIAEYVFVIFMSIELNLKIMADGLFFTPTAVIRDFGGVMDIFIYLVSLIFLCWMPQNVPAESGAQLLMVLRCLRPLRIFKLVPQMRKVVRELFSGFKEIFLVSILLLTLMLVFASFGVQLFAGKLAKCNDPNIIRREDCNGIFRINVSVSKNLNLKLRPGEKKPGFWVPRVWANPRNFNFDNVGNAMLALFEVLSLKGWVEVRDVIIHRVGPIHGIYIHVFVFLGCMIGLTLFVGVVIANFNENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRAKMYDITQHPFFKRTIALLVLAQSVLLSVKWDVEDPVTVPLATMSVVFTFIFVLEVTMKIIAMSPAGFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVIVFRFFSICGKHVTLKMLLLTVVVSMYKSFFIIVGMFLLLLCYAFAGVVLFGTVKYGENINRHANFSSAGKAITVLFRIVTGEDWNKIMHDCMVQPPFCTPDEFTYWATDCGNYAGALMYFCSFYVIIAYIMLNLLVAIIVENFSLFYSTEEDQLLSYNDLRHFQIIWNMVDDKREGVIPTFRVKFLLRLLRGRLEVDLDKDKLLFKHMCYEMERLHNGGDVTFHDVLSMLSYRSVDIRKSLQLEELLAREQLEYTIEEEVAKQTIRMWLKKCLKRIRAKQQQSCSIIHSLRESQQQELSRFLNPPSIETTQPSEDTNANSQDNSMQPETSSQQQLLSPTLSDRGGSRQDAADAGKPQRKFGQWRLPSAPKPISHSVSSVNLRFGGRTTMKSVVCKMNPMTDAASCGSEVKKWWTRQLTVESDESGDDLLDI |
NALCN regulates resting membrane potential and controls neuronal excitability. Neuropeptides, such as neurotensin, activates NALCN through the SRC family kinase-dependent pathway, thereby activating action potentials. In addition, NALCN activity is also associated with several GPCRs, which are involved in systemic osmoregulation by controlling serum sodium concentrations and are required for normal respiratory rhythm and neonatal survival. NALCN is part of the reason for material depolarization and regulation of intestinal pacing activity in stromal cells. Moreover, it plays a key role in maintaining the spontaneous regulation of nigral reticulocytes and the physiological regulation of neuronal excitability.
Fig.1 Structure of voltage-gated sodium channels. (Yu, 2014)
The authors focused on the sodium leak, G protein-coupled receptors (GPCRs)-activated NALCN channel and summarized the existing knowledge of NALCN pathways in physiology and disease.
The authors used homozygous mapping of SNPs, targeted sequencing and profiling exome sequencing in two unrelated families of NALCNs, and finally identified specific mutations that led to autosomal recessive syndrome.
The authors tested infants with idiopathic severe growth retardation and NALCN mutations, suggesting that NALCN is responsible for INAD facial deformity and broadens the genetic profile associated with axonal dystrophy.
This paper showed that NALCN formed a voltage-independent non-selective cation channel that controlled neuronal excitability and affected the respiratory rhythm of mice.
This review reviewed the molecular and evolutionary relationships in the cation channel superfamily, which are associated with a variety of physiological activities.
To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Besides, we also provide customized anti-NALCN antibody development services based on our versatile Magic™ anti-membrane protein antibody discovery platform.
Creative Biolabs' skillful scientists are glad to leverage our expertise and advanced technologies to help you with the member protein research. If you are interested, please feel free to contact us for more details.
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