Protein detail

NALCN

Sodium leak channel NALCN (CanIon) (Sodium leak channel non-selective protein) (Voltage gated channel-like protein 1)

Entry name NALCN	UniProt ID Q8IZF0	EVMP confidence score 0.38
Supporting publications (n) 1	Transmembrane count 24	Protein classification Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Sodium leak channel NALCN (CanIon) (Sodium leak channel non-selective protein) (Voltage gated channel-like protein 1)

Protein Class (7)

Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

Protein Function (5)

Predicted intracellular proteins
Potential drug targets
Transporters:Transporter channels and pores
Disease related genes
Human disease related genes:Congenital malformations:Other congenital malformations

Transmembrane

37..57; Helical; Name=S1 of repeat I; 66..90; Helical; Name=S2 of repeat I; 107..129; Helical; Name=S3 of repeat I; 138..158; Helical; Voltage-sensor; Name=S4 of repeat I; 174..199; Helical; Name=S5 of repeat I; 295..322; Helical; Name=S6 of repeat I; 383..403; Helical; Name=S1 of repeat II; 417..439; Helical; Name=S2 of repeat II; 448..468; Helical; Name=S3 of repeat II; 473..492; Helical; Voltage-sensor; Name=S4 of repeat II; 503..530; Helical; Name=S5 of repeat II; 570..599; Helical; Name=S6 of repeat II; 887..906; Helical; Name=S1 of repeat III; 916..939; Helical; Name=S2 of repeat III; 948..972; Helical; Name=S3 of repeat III; 981..1003; Helical; Voltage-sensor; Name=S4 of repeat III; 1016..1039; Helical; Name=S5 of repeat III; 1130..1159; Helical; Name=S6 of repeat III; 1211..1227; Helical; Name=S1 of repeat IV; 1237..1260; Helical; Name=S2 of repeat IV; 1272..1293; Helical; Name=S3 of repeat IV; 1297..1318; Helical; Voltage-sensor; Name=S4 of repeat IV; 1332..1357; Helical; Name=S5 of repeat IV; 1421..1447; Helical; Name=S6 of repeat IV

Transmembrane Count

Ensembl

ENSG00000102452

Entrez Gene Symbol

NALCN

Gene Synonym (3)

bA430M15.1CanIonVGCNL1

Gene Description

Sodium leak channel, non-selective

Chromosome

Position

101053776-101416508

Supporting publications (n)

EVMP confidence score

0.38

Fluorescence & Localization5

Cell SpecificExtravillous trophoblastsSingle-Nuclei Brain Specificcentral nervous system macrophageSecretome LocationIntracellular and membraneSecretome FunctionImmunity

Function & Pathway6

Protein Function (5)

Predicted intracellular proteins
Potential drug targets
Transporters:Transporter channels and pores
Disease related genes
Human disease related genes:Congenital malformations:Other congenital malformations

Cellular Component (2)

Molecular Function (5)

Biological Process (3)

Reactome (3)

Mediation Categories

Fusion and delivery mediation

Relations & Evidence26

Ligand-Receptor Signaling (24)

24 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
cell_surface	cell_surface	Surfaceome	No	No	No	No	No
cell_surface	cell_surface	OmniPath	No	No	No	No	No
receptor	receptor	scConnect	No	Yes	No	No	No
transmembrane	transmembrane_predicted	Phobius	No	No	No	No	No

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Regulatory Interaction Network (1)

1 record.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
UNC80	Q8N2C7	NALCN	Q8IZF0	Yes	Yes	No	HINTSIGNOR	HINT:35387979 SIGNOR:22196327 HINT:34929720 SIGNOR:19535918

Protein Complex Composition (1)

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	NALCN NALF1	B1AL88 Q8IZF0	1:1	PDB	PDB:6xiwPDB:7cm3

Sequence, Structure & Domains15

Sequences

Length

1,738

Mass

200,331

Sequence

MLKRKQSSRVEAQPVTDFGPDESLSDNADILWINKPWVHSLLRICAIISVISVCMNTPMTFEHYPPLQYVTFTLDTLLMFLYTAEMIAKMHIRGIVKGDSSYVKDRWCVFDGFMVFCLWVSLVLQVFEIADIVDQMSPWGMLRIPRPLIMIRAFRIYFRFELPRTRITNILKRSGEQIWSVSIFLLFFLLLYGILGVQMFGTFTYHCVVNDTKPGNVTWNSLAIPDTHCSPELEEGYQCPPGFKCMDLEDLGLSRQELGYSGFNEIGTSIFTVYEAASQEGWVFLMYRAIDSFPRWRSYFYFITLIFFLAWLVKNVFIAVIIETFAEIRVQFQQMWGSRSSTTSTATTQMFHEDAAGGWQLVAVDVNKPQGRAPACLQKMMRSSVFHMFILSMVTVDVIVAASNYYKGENFRRQYDEFYLAEVAFTVLFDLEALLKIWCLGFTGYISSSLHKFELLLVIGTTLHVYPDLYHSQFTYFQVLRVVRLIKISPALEDFVYKIFGPGKKLGSLVVFTASLLIVMSAISLQMFCFVEELDRFTTFPRAFMSMFQILTQEGWVDVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRESFMKQFIDRQQQDTCCLLRSLPTTSSSSCDHSKRSAIEDNKYIDQKLRKSVFSIRARNLLEKETAVTKILRACTRQRMLSGSFEGQPAKERSILSVQHHIRQERRSLRHGSNSQRISRGKSLETLTQDHSNTVRYRNAQREDSEIKMIQEKKEQAEMKRKVQEEELRENHPYFDKPLFIVGREHRFRNFCRVVVRARFNASKTDPVTGAVKNTKYHQLYDLLGLVTYLDWVMIIVTICSCISMMFESPFRRVMHAPTLQIAEYVFVIFMSIELNLKIMADGLFFTPTAVIRDFGGVMDIFIYLVSLIFLCWMPQNVPAESGAQLLMVLRCLRPLRIFKLVPQMRKVVRELFSGFKEIFLVSILLLTLMLVFASFGVQLFAGKLAKCNDPNIIRREDCNGIFRINVSVSKNLNLKLRPGEKKPGFWVPRVWANPRNFNFDNVGNAMLALFEVLSLKGWVEVRDVIIHRVGPIHGIYIHVFVFLGCMIGLTLFVGVVIANFNENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRAKMYDITQHPFFKRTIALLVLAQSVLLSVKWDVEDPVTVPLATMSVVFTFIFVLEVTMKIIAMSPAGFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVIVFRFFSICGKHVTLKMLLLTVVVSMYKSFFIIVGMFLLLLCYAFAGVVLFGTVKYGENINRHANFSSAGKAITVLFRIVTGEDWNKIMHDCMVQPPFCTPDEFTYWATDCGNYAGALMYFCSFYVIIAYIMLNLLVAIIVENFSLFYSTEEDQLLSYNDLRHFQIIWNMVDDKREGVIPTFRVKFLLRLLRGRLEVDLDKDKLLFKHMCYEMERLHNGGDVTFHDVLSMLSYRSVDIRKSLQLEELLAREQLEYTIEEEVAKQTIRMWLKKCLKRIRAKQQQSCSIIHSLRESQQQELSRFLNPPSIETTQPSEDTNANSQDNSMQPETSSQQQLLSPTLSDRGGSRQDAADAGKPQRKFGQWRLPSAPKPISHSVSSVNLRFGGRTTMKSVVCKMNPMTDAASCGSEVKKWWTRQLTVESDESGDDLLDI

Alternative Products

Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q8IZF0-1; Sequence=Displayed; Name=2; IsoId=Q8IZF0-2; Sequence=VSP_030190, VSP_030191; Name=3; IsoId=Q8IZF0-3; Sequence=VSP_030188, VSP_030189

Alternative Sequence

216..218; NVT -> LSL (in isoform 3); 219..1738; Missing (in isoform 3); 589..668; ILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNRPQMVKISKLPSDFTVPKIRESFMKQFID -> PPSLIRDLCGTQDACPSCLPLQPPNHLPGSQTLARLTHQALTTPPGMRSSQLFSKISLLLGICVAWESILGSLSLSHNLQ (in isoform 2); 669..1738; Missing (in isoform 2)

3D Structural Models

Turn

32..34; 309..311; 467..471; 553..555; 569..571; 912..914; 1040..1042; 1144..1146; 1292..1294; 1387..1390; 1412..1414; 1505..1507; 1522..1524

Helix

37..55; 58..63; 67..90; 108..129; 138..143; 146..149; 150..153; 156..158; 164..199; 219..221; 248..251; 255..258; 266..277; 282..292; 295..308; 312..333; 374..376; 378..381; 384..402; 417..446; 449..464; 475..480; 481..488; 490..499; 503..528; 540..552; 556..566; 572..588; 590..602; 606..615; 630..632; 633..636; 660..668; 714..717; 719..739; 818..829; 836..838; 847..855; 878..882; 887..903; 916..940; 953..971; 981..988; 989..994; 995..999; 1001..1011; 1014..1039; 1054..1056; 1101..1112; 1117..1127; 1130..1132; 1133..1143; 1147..1163; 1170..1184; 1198..1207; 1210..1223; 1224..1228; 1238..1262; 1264..1268; 1272..1291; 1297..1312; 1313..1316; 1319..1334; 1336..1356; 1375..1386; 1391..1397; 1420..1436; 1438..1453; 1464..1477; 1489..1496; 1499..1501; 1509..1521; 1530..1539; 1544..1547; 1550..1570; 1590..1601

Beta Strand

130..133; 160..162; 205..211; 231..236; 243..247; 262..265; 355..357; 409..411; 537..539; 647..649; 830..834; 908..910; 942..945; 949..952; 978..980; 1045..1048; 1059..1065; 1069..1071; 1082..1087; 1166..1168; 1233..1235; 1367..1370; 1459..1461; 1479..1481; 1482..1485; 1525..1529

3D Structure

Electron microscopy (5)

Domain & Motif Annotations

Compositional Bias

1613..1632; Polar residues; 1633..1648; Low complexity

Coiled Coil

795..830

Domain (CC)

Contains 24 transmembrane helices (TM) that form four homologous functional repeats connected by intracellular linkers. Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor. S4 transmembrane segments lack some of the charged residues (K and R) found at every third position in the S4s of the NaV, CaV, and KV channels. Pore-forming loops (P loops) between S5 and S6 of each domain form an EEKE sodium- ion selectivity filter a mixture between the EEEE found in the CaVs and the DEKA of NaVs. Voltage-sensing domains (VSDs), formed by S1 to S4 of each domain, detect changes in membrane potential and induce the opening or closing of the ion-conducting pore domain, formed by S5 and S6..

Region

762..785; Disordered; 1611..1678; Disordered

Protein Families

NALCN family

Sequence Similarities

Belongs to the NALCN family.

Clinical Relevance3

Disease Involvement (2)

Disease variantNeurodegeneration

Drugs (2)

METHOTREXATE ZIPRASIDONE

Antibody (3)

HPA031889 HPA031890 HPA031958

Supporting Publications1

PMID	Title	Abstract
37953466	RAB31 in glioma-derived endothelial cells promotes glioma cell invasion via extracellular vesicle-mediated enrichment of MYO1C.	No abstract available