NALCN_HUMAN
ID NALCN_HUMAN Reviewed; 1738 AA.
AC Q8IZF0; Q6P2S6; Q6ZMI7; Q8IZZ1; Q8TAH1;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Sodium leak channel NALCN {ECO:0000305};
DE AltName: Full=CanIon;
DE AltName: Full=Sodium leak channel non-selective protein;
DE AltName: Full=Voltage gated channel-like protein 1;
GN Name=NALCN {ECO:0000312|HGNC:HGNC:19082};
GN Synonyms=VGCNL1 {ECO:0000303|Ref.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Bonner T.I., Moses T., Detera-Wadleigh S.;
RT "VGCNL1, a putative voltage-gated ion channel.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Bone, and Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-266.
RX PubMed=12364586; DOI=10.1073/pnas.182412499;
RA Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M.,
RA Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A.,
RA Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P.,
RA Maurice K., Essioux L., Millasseau P., Grel P., Debailleul V., Simon A.-M.,
RA Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M.,
RA Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S.,
RA Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S.,
RA Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D.,
RA Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I.,
RA Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P.,
RA Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E.,
RA Weinberger D.R., Cohen N., Cohen D.;
RT "Genetic and physiological data implicating the new human gene G72 and the
RT gene for D-amino acid oxidase in schizophrenia.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13675-13680(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1428-1738.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP FUNCTION.
RX PubMed=17448995; DOI=10.1016/j.cell.2007.02.041;
RA Lu B., Su Y., Das S., Liu J., Xia J., Ren D.;
RT "The neuronal channel NALCN contributes resting sodium permeability and is
RT required for normal respiratory rhythm.";
RL Cell 129:371-383(2007).
RN [8]
RP INVOLVEMENT IN IHPRF1.
RX PubMed=23749988; DOI=10.1136/jmedgenet-2013-101634;
RA Koeroglu C., Seven M., Tolun A.;
RT "Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy
RT with facial dysmorphism.";
RL J. Med. Genet. 50:515-520(2013).
RN [9]
RP INVOLVEMENT IN CLIFAHDD, VARIANTS CLIFAHDD PRO-177; ILE-312; GLY-313;
RP SER-509; SER-578; PHE-590; PRO-1165 AND MET-1446, AND CHARACTERIZATION OF
RP VARIANTS CLIFAHDD SER-509 AND SER-578.
RX PubMed=25683120; DOI=10.1016/j.ajhg.2015.01.003;
RG University of Washington Center for Mendelian Genomics;
RA Chong J.X., McMillin M.J., Shively K.M., Beck A.E., Marvin C.T.,
RA Armenteros J.R., Buckingham K.J., Nkinsi N.T., Boyle E.A., Berry M.N.,
RA Bocian M., Foulds N., Uzielli M.L., Haldeman-Englert C., Hennekam R.C.,
RA Kaplan P., Kline A.D., Mercer C.L., Nowaczyk M.J.,
RA Klein Wassink-Ruiter J.S., McPherson E.W., Moreno R.A., Scheuerle A.E.,
RA Shashi V., Stevens C.A., Carey J.C., Monteil A., Lory P., Tabor H.K.,
RA Smith J.D., Shendure J., Nickerson D.A., Bamshad M.J.;
RT "De novo mutations in NALCN cause a syndrome characterized by congenital
RT contractures of the limbs and face, hypotonia, and developmental delay.";
RL Am. J. Hum. Genet. 96:462-473(2015).
RN [10]
RP CHARACTERIZATION OF VARIANTS CLIFAHDD SER-509 AND SER-578, CHARACTERIZATION
RP OF VARIANT IHPRF1 LEU-1287, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=31409833; DOI=10.1038/s41598-019-48071-x;
RA Bouasse M., Impheng H., Servant Z., Lory P., Monteil A.;
RT "Functional expression of CLIFAHDD and IHPRF pathogenic variants of the
RT NALCN channel in neuronal cells reveals both gain- and loss-of-function
RT properties.";
RL Sci. Rep. 9:11791-11791(2019).
RN [11]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF ARG-146; ARG-152; ARG-155; GLU-280; ARG-481; ARG-484;
RP LYS-487; GLU-554; ASP-558; ASP-561; ARG-989; ARG-992; ARG-995; LYS-1115;
RP GLU-1119; ARG-1310; GLU-1389 AND ASP-1390.
RX PubMed=32494638; DOI=10.1126/sciadv.aaz3154;
RA Chua H.C., Wulf M., Weidling C., Rasmussen L.P., Pless S.A.;
RT "The NALCN channel complex is voltage sensitive and directly modulated by
RT extracellular calcium.";
RL Sci. Adv. 6:eaaz3154-eaaz3154(2020).
RN [12] {ECO:0007744|PDB:6XIW}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH NALF1,
RP FUNCTION, CHARACTERIZATION OF VARIANTS CLIFAHDD PHE-590; GLN-1181 AND
RP MET-1446, CHARACTERIZATION OF VARIANT IHPRF1 LEU-1287, DISULFIDE BOND,
RP GLYCOSYLATION AT ASN-1064, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=32698188; DOI=10.1038/s41586-020-2570-8;
RA Kschonsak M., Chua H.C., Noland C.L., Weidling C., Clairfeuille T.,
RA Bahlke O.O., Ameen A.O., Li Z.R., Arthur C.P., Ciferri C., Pless S.A.,
RA Payandeh J.;
RT "Structure of the human sodium leak channel NALCN.";
RL Nature 587:313-318(2020).
RN [13] {ECO:0007744|PDB:7CM3}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH NALF1,
RP DISULFIDE BONDS, GLYCOSYLATION AT ASN-210; ASN-216 AND ASN-1064, FUNCTION,
RP MUTAGENESIS OF PHE-325; ILE-328; PHE-332; LYS-504 AND LYS-505, AND ACTIVITY
RP REGULATION.
RX PubMed=33203861; DOI=10.1038/s41467-020-19667-z;
RA Xie J., Ke M., Xu L., Lin S., Huang J., Zhang J., Yang F., Wu J., Yan Z.;
RT "Structure of the human sodium leak channel NALCN in complex with
RT FAM155A.";
RL Nat. Commun. 11:5831-5831(2020).
RN [14]
RP VARIANT IHPRF1 LEU-1287.
RX PubMed=24075186; DOI=10.1016/j.ajhg.2013.08.001;
RA Al-Sayed M.D., Al-Zaidan H., Albakheet A., Hakami H., Kenana R.,
RA Al-Yafee Y., Al-Dosary M., Qari A., Al-Sheddi T., Al-Muheiza M.,
RA Al-Qubbaj W., Lakmache Y., Al-Hindi H., Ghaziuddin M., Colak D., Kaya N.;
RT "Mutations in NALCN cause an autosomal-recessive syndrome with severe
RT hypotonia, speech impairment, and cognitive delay.";
RL Am. J. Hum. Genet. 93:721-726(2013).
RN [15]
RP VARIANT GLN-1181.
RX PubMed=25864427; DOI=10.1002/humu.22797;
RA Aoyagi K., Rossignol E., Hamdan F.F., Mulcahy B., Xie L., Nagamatsu S.,
RA Rouleau G.A., Zhen M., Michaud J.L.;
RT "A gain-of-function mutation in NALCN in a child with intellectual
RT disability, ataxia, and arthrogryposis.";
RL Hum. Mutat. 36:753-757(2015).
RN [16]
RP VARIANTS VAL-312; PHE-1020 AND GLN-1181.
RX PubMed=26763878; DOI=10.1038/jhg.2015.163;
RA Fukai R., Saitsu H., Okamoto N., Sakai Y., Fattal-Valevski A., Masaaki S.,
RA Kitai Y., Torio M., Kojima-Ishii K., Ihara K., Chernuha V., Nakashima M.,
RA Miyatake S., Tanaka F., Miyake N., Matsumoto N.;
RT "De novo missense mutations in NALCN cause developmental and intellectual
RT impairment with hypotonia.";
RL J. Hum. Genet. 61:451-455(2016).
RN [17]
RP VARIANTS CYS-317 AND PHE-595.
RX PubMed=27214504; DOI=10.1055/s-0036-1584084;
RA Karakaya M., Heller R., Kunde V., Zimmer K.P., Chao C.M., Nuernberg P.,
RA Cirak S.;
RT "Novel mutations in the nonselective sodium leak channel (NALCN) lead to
RT distal arthrogryposis with increased muscle tone.";
RL Neuropediatrics 47:273-277(2016).
CC -!- FUNCTION: Voltage-gated ion channel responsible for the resting Na(+)
CC permeability that controls neuronal excitability (PubMed:17448995,
CC PubMed:31409833). NALCN channel functions as a multi-protein complex,
CC which consists at least of NALCN, NALF1, UNC79 and UNC80
CC (PubMed:32494638, PubMed:33203861). NALCN is the voltage-sensing, pore-
CC forming subunit of the NALCN channel complex (PubMed:17448995). NALCN
CC channel complex is constitutively active and conducts monovalent
CC cations but is blocked by physiological concentrations of extracellular
CC divalent cations (PubMed:32494638). In addition to its role in
CC regulating neuronal excitability, is required for normal respiratory
CC rhythm, systemic osmoregulation by controlling the serum sodium
CC concentration and in the regulation of the intestinal pace-making
CC activity in the interstitial cells of Cajal (By similarity). NALCN
CC channel is also activated by neuropeptides such as neurotensin and
CC substance P (SP) through a SRC family kinases-dependent pathway (By
CC similarity). In addition, NALCN activity is enhanced/modulated by
CC several GPCRs, such as CHRM3 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BXR5, ECO:0000269|PubMed:17448995,
CC ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32494638,
CC ECO:0000269|PubMed:33203861}.
CC -!- ACTIVITY REGULATION: Inhibited by low micromolar concentrations of
CC Gd(3+) and high micromolar concentrations of verapamil. Insensitive to
CC tetrodotoxin (TTX) and potentiated by low external Ca(2+)
CC concentration. {ECO:0000269|PubMed:32494638,
CC ECO:0000269|PubMed:33203861}.
CC -!- SUBUNIT: Found in a complex with NALCN, UNC79, UNC80 and NACL1; these
CC auxiliary subunits are indispensable for the function of NALCN channel
CC (PubMed:32494638, PubMed:32698188, PubMed:33203861). Interacts with
CC UNC80; required for the NALCN activation/inhibition by GPCRs in
CC neurons. Found in a complex with NALCN, UNC79 and UNC80; UNC80 bridges
CC NALCN to UNC79 (By similarity). Interacts with CHRM3 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BXR5, ECO:0000269|PubMed:32494638,
CC ECO:0000269|PubMed:32698188, ECO:0000269|PubMed:33203861}.
CC -!- INTERACTION:
CC Q8IZF0; P20309: CHRM3; NbExp=3; IntAct=EBI-7085333, EBI-2687785;
CC Q8IZF0; P50222: MEOX2; NbExp=3; IntAct=EBI-7085333, EBI-748397;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31409833,
CC ECO:0000269|PubMed:32494638, ECO:0000269|PubMed:32698188}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IZF0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZF0-2; Sequence=VSP_030190, VSP_030191;
CC Name=3;
CC IsoId=Q8IZF0-3; Sequence=VSP_030188, VSP_030189;
CC -!- DOMAIN: Contains 24 transmembrane helices (TM) that form four
CC homologous functional repeats connected by intracellular linkers. Each
CC of the four internal repeats contains five hydrophobic transmembrane
CC segments (S1, S2, S3, S5, S6) and one positively charged transmembrane
CC segment (S4). S4 segments represent the voltage-sensor. S4
CC transmembrane segments lack some of the charged residues (K and R)
CC found at every third position in the S4s of the NaV, CaV, and KV
CC channels. Pore-forming loops (P loops) between S5 and S6 of each domain
CC form an EEKE sodium- ion selectivity filter a mixture between the EEEE
CC found in the CaVs and the DEKA of NaVs. Voltage-sensing domains (VSDs),
CC formed by S1 to S4 of each domain, detect changes in membrane potential
CC and induce the opening or closing of the ion-conducting pore domain,
CC formed by S5 and S6. {ECO:0000250|UniProtKB:Q8BXR5}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q8BXR5}.
CC -!- DISEASE: Hypotonia, infantile, with psychomotor retardation and
CC characteristic facies 1 (IHPRF1) [MIM:615419]: A neurodegenerative
CC disease characterized by variable degrees of hypotonia, speech
CC impairment, intellectual disability, pyramidal signs, subtle facial
CC dysmorphism, and chronic constipation. Some patients manifest
CC neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid
CC bodies in tissue biopsies. {ECO:0000269|PubMed:23749988,
CC ECO:0000269|PubMed:24075186, ECO:0000269|PubMed:31409833,
CC ECO:0000269|PubMed:32698188}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Congenital contractures of the limbs and face, hypotonia, and
CC developmental delay (CLIFAHDD) [MIM:616266]: A disease characterized by
CC congenital contractures of the limbs and face, resulting in
CC characteristic facial features, abnormal tone, most commonly manifested
CC as hypotonia, and variable degrees of developmental delay.
CC {ECO:0000269|PubMed:25683120, ECO:0000269|PubMed:31409833,
CC ECO:0000269|PubMed:32698188}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NALCN family. {ECO:0000305}.
CC -!- CAUTION: NALCN was also originally reported to be a voltage-
CC independent, cation-nonselective channel which is permeable to sodium,
CC potassium and calcium ions (PubMed:17448995). However, NALCN is
CC recently reported to be selective only for monovalent cations and to be
CC blocked by extracellular divalent cations (PubMed:32494638). Futhemore,
CC coexpression of NALCN, UNC79, UNC80, and NALF1 results in voltage-
CC dependent NALCN currents (PubMed:32494638, PubMed:31409833).
CC {ECO:0000269|PubMed:17448995, ECO:0000269|PubMed:31409833,
CC ECO:0000269|PubMed:32494638}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD18738.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY141972; AAN10255.1; -; mRNA.
DR EMBL; AL138707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354891; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX09045.1; -; Genomic_DNA.
DR EMBL; BC028390; AAH28390.1; -; mRNA.
DR EMBL; BC064343; AAH64343.1; -; mRNA.
DR EMBL; AE014293; AAN16023.1; -; Genomic_DNA.
DR EMBL; AK172752; BAD18738.1; ALT_INIT; mRNA.
DR CCDS; CCDS9498.1; -. [Q8IZF0-1]
DR RefSeq; NP_443099.1; NM_052867.2. [Q8IZF0-1]
DR RefSeq; XP_011519370.1; XM_011521068.2.
DR PDB; 6XIW; EM; 2.80 A; A=1-1738.
DR PDB; 7CM3; EM; 3.10 A; A=1-1738.
DR PDB; 7SX3; EM; 3.10 A; A=1-1738.
DR PDB; 7SX4; EM; 3.50 A; A=1-1738.
DR PDBsum; 6XIW; -.
DR PDBsum; 7CM3; -.
DR PDBsum; 7SX3; -.
DR PDBsum; 7SX4; -.
DR AlphaFoldDB; Q8IZF0; -.
DR SMR; Q8IZF0; -.
DR BioGRID; 129228; 4.
DR IntAct; Q8IZF0; 5.
DR MINT; Q8IZF0; -.
DR STRING; 9606.ENSP00000251127; -.
DR GuidetoPHARMACOLOGY; 750; -.
DR TCDB; 1.A.1.11.15; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q8IZF0; -.
DR PhosphoSitePlus; Q8IZF0; -.
DR SwissPalm; Q8IZF0; -.
DR BioMuta; NALCN; -.
DR DMDM; 74750791; -.
DR jPOST; Q8IZF0; -.
DR MassIVE; Q8IZF0; -.
DR PaxDb; Q8IZF0; -.
DR PeptideAtlas; Q8IZF0; -.
DR PRIDE; Q8IZF0; -.
DR ProteomicsDB; 71335; -. [Q8IZF0-1]
DR Antibodypedia; 25282; 103 antibodies from 15 providers.
DR DNASU; 259232; -.
DR Ensembl; ENST00000251127.11; ENSP00000251127.6; ENSG00000102452.18. [Q8IZF0-1]
DR Ensembl; ENST00000376200.6; ENSP00000365373.5; ENSG00000102452.18. [Q8IZF0-3]
DR GeneID; 259232; -.
DR KEGG; hsa:259232; -.
DR MANE-Select; ENST00000251127.11; ENSP00000251127.6; NM_052867.4; NP_443099.1.
DR UCSC; uc001vox.2; human. [Q8IZF0-1]
DR CTD; 259232; -.
DR DisGeNET; 259232; -.
DR GeneCards; NALCN; -.
DR HGNC; HGNC:19082; NALCN.
DR HPA; ENSG00000102452; Tissue enhanced (brain).
DR MalaCards; NALCN; -.
DR MIM; 611549; gene.
DR MIM; 615419; phenotype.
DR MIM; 616266; phenotype.
DR neXtProt; NX_Q8IZF0; -.
DR OpenTargets; ENSG00000102452; -.
DR Orphanet; 562528; Congenital limbs-face contractures-hypotonia-developmental delay syndrome.
DR Orphanet; 1146; Distal arthrogryposis type 1.
DR Orphanet; 2053; Freeman-Sheldon syndrome.
DR Orphanet; 371364; Hypotonia-speech impairment-severe cognitive delay syndrome.
DR Orphanet; 1147; Sheldon-Hall syndrome.
DR PharmGKB; PA162396840; -.
DR VEuPathDB; HostDB:ENSG00000102452; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000156023; -.
DR HOGENOM; CLU_000984_0_0_1; -.
DR InParanoid; Q8IZF0; -.
DR OMA; TLFIAWN; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q8IZF0; -.
DR TreeFam; TF312843; -.
DR PathwayCommons; Q8IZF0; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q8IZF0; -.
DR SIGNOR; Q8IZF0; -.
DR BioGRID-ORCS; 259232; 5 hits in 1067 CRISPR screens.
DR ChiTaRS; NALCN; human.
DR GenomeRNAi; 259232; -.
DR Pharos; Q8IZF0; Tchem.
DR PRO; PR:Q8IZF0; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q8IZF0; protein.
DR Bgee; ENSG00000102452; Expressed in middle temporal gyrus and 141 other tissues.
DR ExpressionAtlas; Q8IZF0; baseline and differential.
DR Genevisible; Q8IZF0; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; ISS:UniProtKB.
DR GO; GO:0022840; F:leak channel activity; ISS:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; TAS:Reactome.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0032224; P:positive regulation of synaptic transmission, cholinergic; IBA:GO_Central.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0060075; P:regulation of resting membrane potential; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028823; NALCN.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46141; PTHR46141; 1.
DR Pfam; PF00520; Ion_trans; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Coiled coil;
KW Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Neurodegeneration; Reference proteome; Repeat; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..1738
FT /note="Sodium leak channel NALCN"
FT /id="PRO_0000314010"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 37..57
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 58..65
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 66..90
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 91..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 107..129
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 130..137
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 138..158
FT /note="Helical; Voltage-sensor; Name=S4 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 159..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 174..199
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 200..269
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT INTRAMEM 270..289
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 290..294
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 295..322
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 323..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 383..403
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 404..416
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 417..439
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 440..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 448..468
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 469..472
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 473..492
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 493..502
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 503..530
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 531..543
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT INTRAMEM 544..563
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 564..569
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 570..599
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 600..886
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 887..906
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 907..915
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 916..939
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 940..947
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 948..972
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 973..980
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 981..1003
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1004..1015
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1016..1039
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1040..1104
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT INTRAMEM 1105..1124
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1125..1129
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1130..1159
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1160..1210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1211..1227
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1228..1236
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1237..1260
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1261..1271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1272..1293
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1294..1296
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1297..1318
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1319..1331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1332..1357
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1358..1378
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT INTRAMEM 1379..1398
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1399..1420
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TRANSMEM 1421..1447
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT TOPO_DOM 1448..1738
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0007744|PDB:6XIW"
FT REGION 762..785
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1611..1678
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 795..830
FT /evidence="ECO:0000255"
FT COMPBIAS 1611..1651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:33203861,
FT ECO:0007744|PDB:7CM3"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:33203861,
FT ECO:0007744|PDB:7CM3"
FT CARBOHYD 1064
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0000269|PubMed:33203861, ECO:0007744|PDB:6XIW,
FT ECO:0007744|PDB:7CM3"
FT DISULFID 207..239
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0000269|PubMed:33203861, ECO:0007744|PDB:6XIW,
FT ECO:0007744|PDB:7CM3"
FT DISULFID 229..245
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0000269|PubMed:33203861, ECO:0007744|PDB:6XIW,
FT ECO:0007744|PDB:7CM3"
FT DISULFID 1046..1057
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0000269|PubMed:33203861, ECO:0007744|PDB:6XIW,
FT ECO:0007744|PDB:7CM3"
FT DISULFID 1405..1417
FT /evidence="ECO:0000269|PubMed:32698188,
FT ECO:0000269|PubMed:33203861, ECO:0007744|PDB:6XIW,
FT ECO:0007744|PDB:7CM3"
FT VAR_SEQ 216..218
FT /note="NVT -> LSL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030188"
FT VAR_SEQ 219..1738
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030189"
FT VAR_SEQ 589..668
FT /note="ILLSLFVAVILDNLELDEDLKKLKQLKQSEANADTKEKLPLRLRIFEKFPNR
FT PQMVKISKLPSDFTVPKIRESFMKQFID -> PPSLIRDLCGTQDACPSCLPLQPPNHL
FT PGSQTLARLTHQALTTPPGMRSSQLFSKISLLLGICVAWESILGSLSLSHNLQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030190"
FT VAR_SEQ 669..1738
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030191"
FT VARIANT 177
FT /note="Q -> P (in CLIFAHDD; dbSNP:rs786203984)"
FT /evidence="ECO:0000269|PubMed:25683120"
FT /id="VAR_073361"
FT VARIANT 312
FT /note="L -> I (in CLIFAHDD; dbSNP:rs878853134)"
FT /evidence="ECO:0000269|PubMed:25683120"
FT /id="VAR_073362"
FT VARIANT 312
FT /note="L -> V (found in patients with neurodevelopmental
FT disease and hypotonia; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:26763878"
FT /id="VAR_076674"
FT VARIANT 313
FT /note="V -> G (in CLIFAHDD; dbSNP:rs786203985)"
FT /evidence="ECO:0000269|PubMed:25683120"
FT /id="VAR_073363"
FT VARIANT 317
FT /note="F -> C (found in patients with distal arthrogryposis
FT and central hypertonia; unknown pathological significance;
FT dbSNP:rs1594616249)"
FT /evidence="ECO:0000269|PubMed:27214504"
FT /id="VAR_076675"
FT VARIANT 509
FT /note="L -> S (in CLIFAHDD and IHPRF1; nearly eliminates
FT wild-type protein expression; dominant-negative mutation;
FT decreases membrane expression; induces higher current
FT density and slower inactivation; dbSNP:rs786203987)"
FT /evidence="ECO:0000269|PubMed:25683120,
FT ECO:0000269|PubMed:31409833"
FT /id="VAR_073364"
FT VARIANT 578
FT /note="Y -> S (in CLIFAHDD and IHPRF1; nearly eliminates
FT wild-type protein expression; dominant-negative mutation;
FT decreases membrane expressioninduces higher current density
FT and slower inactivation; dbSNP:rs786203988)"
FT /evidence="ECO:0000269|PubMed:25683120,
FT ECO:0000269|PubMed:31409833"
FT /id="VAR_073365"
FT VARIANT 590
FT /note="L -> F (in CLIFAHDD; dbSNP:rs786203986)"
FT /evidence="ECO:0000269|PubMed:25683120,
FT ECO:0000269|PubMed:32698188"
FT /id="VAR_073366"
FT VARIANT 595
FT /note="V -> F (found in patients with distal arthrogryposis
FT and central hypertonia; unknown pathological significance;
FT dbSNP:rs1594368753)"
FT /evidence="ECO:0000269|PubMed:27214504"
FT /id="VAR_076676"
FT VARIANT 1020
FT /note="V -> F (found in patients with neurodevelopmental
FT disease and hypotonia; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:26763878"
FT /id="VAR_076677"
FT VARIANT 1165
FT /note="T -> P (in CLIFAHDD; dbSNP:rs878853128)"
FT /evidence="ECO:0000269|PubMed:25683120"
FT /id="VAR_073367"
FT VARIANT 1181
FT /note="R -> Q (in CLIFAHDD; found in patients with
FT neurodevelopmental disease and hypotonia; unknown
FT pathological significance; dbSNP:rs786201003)"
FT /evidence="ECO:0000269|PubMed:25864427,
FT ECO:0000269|PubMed:26763878, ECO:0000269|PubMed:32698188"
FT /id="VAR_076678"
FT VARIANT 1287
FT /note="W -> L (in IHPRF1; loss of function;
FT dbSNP:rs587777068)"
FT /evidence="ECO:0000269|PubMed:24075186,
FT ECO:0000269|PubMed:31409833, ECO:0000269|PubMed:32698188"
FT /id="VAR_070599"
FT VARIANT 1446
FT /note="I -> M (in CLIFAHDD; dbSNP:rs878853127)"
FT /evidence="ECO:0000269|PubMed:25683120,
FT ECO:0000269|PubMed:32698188"
FT /id="VAR_073368"
FT MUTAGEN 146
FT /note="R->Q: Affects voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 152
FT /note="R->Q: Affects voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 155
FT /note="R->Q: Affects voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 280
FT /note="E->A: Drastically more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 325
FT /note="F->A: Increases channel activity."
FT /evidence="ECO:0000269|PubMed:33203861"
FT MUTAGEN 328
FT /note="I->W: Increases channel activity."
FT /evidence="ECO:0000269|PubMed:33203861"
FT MUTAGEN 332
FT /note="F->A: No effect on the channel activity."
FT /evidence="ECO:0000269|PubMed:33203861"
FT MUTAGEN 481
FT /note="R->Q: Exhibits altered current kinetics."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 484
FT /note="R->Q: Does not exhibited altered current kinetics."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 487
FT /note="K->Q: Does not exhibited altered current kinetics."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 504
FT /note="K->D,A: Decreases channel activity."
FT /evidence="ECO:0000269|PubMed:33203861"
FT MUTAGEN 505
FT /note="K->A: Decreases channel activity."
FT /evidence="ECO:0000269|PubMed:33203861"
FT MUTAGEN 554
FT /note="E->A: Drastically more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 558
FT /note="D->A: Moderately more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 561
FT /note="D->A: No effect on the blockage of NALCN pore by
FT Ca(2+)."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 989
FT /note="R->Q: Does not affect the voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 992
FT /note="R->Q: Does not affect the voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 995
FT /note="R->Q: Does not affect the voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 1115
FT /note="K->A: No effect on the blockage of NALCN pore by
FT Ca(2+)."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 1119
FT /note="E->A: Moderately more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 1310
FT /note="R->Q: Does not affect the voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 1389
FT /note="E->A: Moderately more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT MUTAGEN 1390
FT /note="D->A: Drastically more sensitive to Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:32494638"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 37..55
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 67..90
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 108..129
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 164..199
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 266..277
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 282..292
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 295..308
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 312..333
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 384..402
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 417..446
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 449..464
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 467..471
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 475..480
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 481..488
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 490..499
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 503..528
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 540..552
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 553..555
FT /evidence="ECO:0007829|PDB:7SX4"
FT HELIX 556..566
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 569..571
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 572..588
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 590..602
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 606..615
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 630..632
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 633..636
FT /evidence="ECO:0007829|PDB:7SX3"
FT STRAND 647..649
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 660..668
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 714..717
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 719..739
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 818..829
FT /evidence="ECO:0007829|PDB:7SX3"
FT STRAND 830..834
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 836..838
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 847..855
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 878..882
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 887..903
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 908..910
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 912..914
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 916..940
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 942..945
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 949..952
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 953..971
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 978..980
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 981..988
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 989..994
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 995..999
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1001..1011
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1014..1039
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1040..1042
FT /evidence="ECO:0007829|PDB:7SX3"
FT STRAND 1045..1048
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1054..1056
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1059..1065
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1069..1071
FT /evidence="ECO:0007829|PDB:7CM3"
FT STRAND 1082..1087
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1101..1112
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1117..1127
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1130..1132
FT /evidence="ECO:0007829|PDB:7SX3"
FT HELIX 1133..1143
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1144..1146
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1147..1163
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1166..1168
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1170..1184
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1198..1207
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1210..1223
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1224..1228
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1233..1235
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 1238..1262
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1264..1268
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1272..1291
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1292..1294
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1297..1312
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1313..1316
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1319..1334
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1336..1356
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1367..1370
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1375..1386
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1387..1390
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1391..1397
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1412..1414
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 1420..1436
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1438..1453
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1459..1461
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1464..1477
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1479..1481
FT /evidence="ECO:0007829|PDB:7SX3"
FT STRAND 1482..1485
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1489..1496
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1499..1501
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1505..1507
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1509..1521
FT /evidence="ECO:0007829|PDB:6XIW"
FT TURN 1522..1524
FT /evidence="ECO:0007829|PDB:6XIW"
FT STRAND 1525..1529
FT /evidence="ECO:0007829|PDB:7CM3"
FT HELIX 1530..1539
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1544..1547
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1550..1570
FT /evidence="ECO:0007829|PDB:6XIW"
FT HELIX 1590..1601
FT /evidence="ECO:0007829|PDB:6XIW"
SQ SEQUENCE 1738 AA; 200331 MW; 296BB66C9E443151 CRC64;
MLKRKQSSRV EAQPVTDFGP DESLSDNADI LWINKPWVHS LLRICAIISV ISVCMNTPMT
FEHYPPLQYV TFTLDTLLMF LYTAEMIAKM HIRGIVKGDS SYVKDRWCVF DGFMVFCLWV
SLVLQVFEIA DIVDQMSPWG MLRIPRPLIM IRAFRIYFRF ELPRTRITNI LKRSGEQIWS
VSIFLLFFLL LYGILGVQMF GTFTYHCVVN DTKPGNVTWN SLAIPDTHCS PELEEGYQCP
PGFKCMDLED LGLSRQELGY SGFNEIGTSI FTVYEAASQE GWVFLMYRAI DSFPRWRSYF
YFITLIFFLA WLVKNVFIAV IIETFAEIRV QFQQMWGSRS STTSTATTQM FHEDAAGGWQ
LVAVDVNKPQ GRAPACLQKM MRSSVFHMFI LSMVTVDVIV AASNYYKGEN FRRQYDEFYL
AEVAFTVLFD LEALLKIWCL GFTGYISSSL HKFELLLVIG TTLHVYPDLY HSQFTYFQVL
RVVRLIKISP ALEDFVYKIF GPGKKLGSLV VFTASLLIVM SAISLQMFCF VEELDRFTTF
PRAFMSMFQI LTQEGWVDVM DQTLNAVGHM WAPVVAIYFI LYHLFATLIL LSLFVAVILD
NLELDEDLKK LKQLKQSEAN ADTKEKLPLR LRIFEKFPNR PQMVKISKLP SDFTVPKIRE
SFMKQFIDRQ QQDTCCLLRS LPTTSSSSCD HSKRSAIEDN KYIDQKLRKS VFSIRARNLL
EKETAVTKIL RACTRQRMLS GSFEGQPAKE RSILSVQHHI RQERRSLRHG SNSQRISRGK
SLETLTQDHS NTVRYRNAQR EDSEIKMIQE KKEQAEMKRK VQEEELRENH PYFDKPLFIV
GREHRFRNFC RVVVRARFNA SKTDPVTGAV KNTKYHQLYD LLGLVTYLDW VMIIVTICSC
ISMMFESPFR RVMHAPTLQI AEYVFVIFMS IELNLKIMAD GLFFTPTAVI RDFGGVMDIF
IYLVSLIFLC WMPQNVPAES GAQLLMVLRC LRPLRIFKLV PQMRKVVREL FSGFKEIFLV
SILLLTLMLV FASFGVQLFA GKLAKCNDPN IIRREDCNGI FRINVSVSKN LNLKLRPGEK
KPGFWVPRVW ANPRNFNFDN VGNAMLALFE VLSLKGWVEV RDVIIHRVGP IHGIYIHVFV
FLGCMIGLTL FVGVVIANFN ENKGTALLTV DQRRWEDLKS RLKIAQPLHL PPRPDNDGFR
AKMYDITQHP FFKRTIALLV LAQSVLLSVK WDVEDPVTVP LATMSVVFTF IFVLEVTMKI
IAMSPAGFWQ SRRNRYDLLV TSLGVVWVVL HFALLNAYTY MMGACVIVFR FFSICGKHVT
LKMLLLTVVV SMYKSFFIIV GMFLLLLCYA FAGVVLFGTV KYGENINRHA NFSSAGKAIT
VLFRIVTGED WNKIMHDCMV QPPFCTPDEF TYWATDCGNY AGALMYFCSF YVIIAYIMLN
LLVAIIVENF SLFYSTEEDQ LLSYNDLRHF QIIWNMVDDK REGVIPTFRV KFLLRLLRGR
LEVDLDKDKL LFKHMCYEME RLHNGGDVTF HDVLSMLSYR SVDIRKSLQL EELLAREQLE
YTIEEEVAKQ TIRMWLKKCL KRIRAKQQQS CSIIHSLRES QQQELSRFLN PPSIETTQPS
EDTNANSQDN SMQPETSSQQ QLLSPTLSDR GGSRQDAADA GKPQRKFGQW RLPSAPKPIS
HSVSSVNLRF GGRTTMKSVV CKMNPMTDAA SCGSEVKKWW TRQLTVESDE SGDDLLDI
