SCNBA_HUMAN
ID SCNBA_HUMAN Reviewed; 1791 AA.
AC Q9UI33; A6NN05; C9JD48; C9JR31; Q68K15; Q8NDX3; Q9UHE0; Q9UHM0;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Sodium channel protein type 11 subunit alpha;
DE AltName: Full=Peripheral nerve sodium channel 5;
DE Short=PN5;
DE AltName: Full=Sensory neuron sodium channel 2;
DE AltName: Full=Sodium channel protein type XI subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.9;
DE AltName: Full=hNaN;
GN Name=SCN11A; Synonyms=SCN12A, SNS2;
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), AND FUNCTION IN VOLTAGE-EVOKED
RP DEPOLARIZATION.
RC TISSUE=Spinal ganglion;
RX PubMed=10580103; DOI=10.1016/s0014-5793(99)01519-7;
RA Dib-Hajj S.D., Tyrrell L., Cummins T.R., Black J.A., Wood P.M.,
RA Waxman S.G.;
RT "Two tetrodotoxin-resistant sodium channels in human dorsal root ganglion
RT neurons.";
RL FEBS Lett. 462:117-120(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10623608; DOI=10.1006/bbrc.1999.1916;
RA Jeong S.-Y., Goto J., Hashida H., Suzuki T., Ogata K., Masuda M., Hirai M.,
RA Isahara K., Uchiyama Y., Kanazawa I.;
RT "Identification of a novel human voltage-gated sodium channel alpha subunit
RT gene, SCN12A.";
RL Biochem. Biophys. Res. Commun. 267:262-270(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN NEUROTROPHIN-EVOKED
RP DEPOLARIZATION.
RC TISSUE=Neuroblastoma;
RX PubMed=12384689; DOI=10.1038/nature01085;
RA Blum R., Kafitz K.W., Konnerth A.;
RT "Neurotrophin-evoked depolarization requires the sodium channel Nav1.9.";
RL Nature 419:687-693(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 924-1114 (ISOFORM 3), AND TISSUE SPECIFICITY.
RC TISSUE=Spinal ganglion;
RX PubMed=15302875; DOI=10.1074/jbc.m406387200;
RA Raymond C.K., Castle J.C., Garrett-Engele P.W., Armour C.D., Kan Z.G.,
RA Tsinoremas N.T., Johnson J.M.;
RT "Expression of alternatively spliced sodium channel alpha-subunit genes:
RT unique splicing patterns are observed in dorsal root ganglia.";
RL J. Biol. Chem. 279:46234-46241(2004).
RN [6]
RP REVIEW.
RX PubMed=12536125; DOI=10.1016/s0166-2236(02)00030-9;
RA Delmas P., Coste B.;
RT "Na+ channel Nav1.9: in search of a gating mechanism.";
RL Trends Neurosci. 26:55-57(2003).
RN [7]
RP VARIANTS FEPS3 CYS-225 AND GLY-808.
RX PubMed=24207120; DOI=10.1016/j.ajhg.2013.09.016;
RA Zhang X.Y., Wen J., Yang W., Wang C., Gao L., Zheng L.H., Wang T., Ran K.,
RA Li Y., Li X., Xu M., Luo J., Feng S., Ma X., Ma H., Chai Z., Zhou Z.,
RA Yao J., Zhang X., Liu J.Y.;
RT "Gain-of-function mutations in SCN11A cause familial episodic pain.";
RL Am. J. Hum. Genet. 93:957-966(2013).
RN [8]
RP VARIANT HSAN7 PRO-811, AND CHARACTERIZATION OF VARIANT HSAN7 PRO-811.
RX PubMed=24036948; DOI=10.1038/ng.2767;
RA Leipold E., Liebmann L., Korenke G.C., Heinrich T., Giesselmann S.,
RA Baets J., Ebbinghaus M., Goral R.O., Stodberg T., Hennings J.C.,
RA Bergmann M., Altmuller J., Thiele H., Wetzel A., Nurnberg P., Timmerman V.,
RA De Jonghe P., Blum R., Schaible H.G., Weis J., Heinemann S.H., Hubner C.A.,
RA Kurth I.;
RT "A de novo gain-of-function mutation in SCN11A causes loss of pain
RT perception.";
RL Nat. Genet. 45:1399-1404(2013).
RN [9]
RP VARIANTS FEPS3 THR-381 AND PRO-1158, VARIANTS ASN-419; THR-582; ASP-681;
RP PRO-842 AND LEU-1689, AND CHARACTERIZATION OF VARIANTS FEPS3 THR-381 AND
RP PRO-1158.
RX PubMed=24776970; DOI=10.1093/brain/awu079;
RG PROPANE Study Group;
RA Huang J., Han C., Estacion M., Vasylyev D., Hoeijmakers J.G., Gerrits M.M.,
RA Tyrrell L., Lauria G., Faber C.G., Dib-Hajj S.D., Merkies I.S.,
RA Waxman S.G.;
RT "Gain-of-function mutations in sodium channel Na(v)1.9 in painful
RT neuropathy.";
RL Brain 137:1627-1642(2014).
RN [10]
RP VARIANT HSAN7 ALA-1184, AND CHARACTERIZATION OF VARIANTS HSAN7 PRO-811 AND
RP ALA-1184.
RX PubMed=26645915; DOI=10.1038/ncomms10049;
RA Leipold E., Hanson-Kahn A., Frick M., Gong P., Bernstein J.A., Voigt M.,
RA Katona I., Oliver Goral R., Altmueller J., Nuernberg P., Weis J.,
RA Huebner C.A., Heinemann S.H., Kurth I.;
RT "Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel
RT mutant.";
RL Nat. Commun. 6:10049-10049(2015).
RN [11]
RP VARIANT FEPS3 ARG-699, AND CHARACTERIZATION OF VARIANT FEPS3 ARG-699.
RX PubMed=25791876; DOI=10.1007/s12017-015-8347-9;
RA Han C., Yang Y., de Greef B.T., Hoeijmakers J.G., Gerrits M.M.,
RA Verhamme C., Qu J., Lauria G., Merkies I.S., Faber C.G., Dib-Hajj S.D.,
RA Waxman S.G.;
RT "The domain II S4-S5 linker in Nav1.9: a missense mutation enhances
RT activation, impairs fast inactivation, and produces human painful
RT neuropathy.";
RL NeuroMolecular Med. 17:158-169(2015).
RN [12]
RP VARIANTS FEPS3 HIS-222 AND SER-222, AND VARIANTS LEU-308; ILE-909 AND
RP ILE-1609.
RX PubMed=27224030; DOI=10.1371/journal.pone.0154827;
RA Okuda H., Noguchi A., Kobayashi H., Kondo D., Harada K.H., Youssefian S.,
RA Shioi H., Kabata R., Domon Y., Kubota K., Kitano Y., Takayama Y.,
RA Hitomi T., Ohno K., Saito Y., Asano T., Tominaga M., Takahashi T.,
RA Koizumi A.;
RT "Infantile pain episodes associated with novel Nav1.9 mutations in familial
RT episodic pain syndrome in japanese families.";
RL PLoS ONE 11:E0154827-E0154827(2016).
CC -!- FUNCTION: This protein mediates the voltage-dependent sodium ion
CC permeability of excitable membranes. Assuming opened or closed
CC conformations in response to the voltage difference across the
CC membrane, the protein forms a sodium-selective channel through which
CC sodium ions may pass in accordance with their electrochemical gradient.
CC It is a tetrodotoxin-resistant sodium channel isoform. Also involved,
CC with the contribution of the receptor tyrosine kinase NTRK2, in rapid
CC BDNF-evoked neuronal depolarization. {ECO:0000269|PubMed:10580103,
CC ECO:0000269|PubMed:12384689}.
CC -!- SUBUNIT: The voltage-resistant sodium channel consists of an ion
CC conducting pore forming alpha-subunit regulated by one or more
CC auxiliary subunits SCN1B, SCN2B and SCN3B.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:D0E0C2};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UI33-1; Sequence=Displayed;
CC Name=2; Synonyms=Scn12a-s;
CC IsoId=Q9UI33-2; Sequence=VSP_012260, VSP_012261;
CC Name=3;
CC IsoId=Q9UI33-3; Sequence=VSP_012259;
CC -!- TISSUE SPECIFICITY: Expressed in the dorsal root ganglia and trigeminal
CC ganglia, olfactory bulb, hippocampus, cerebellar cortex, spinal cord,
CC spleen, small intestine and placenta. {ECO:0000269|PubMed:10623608,
CC ECO:0000269|PubMed:15302875}.
CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged
CC segment (S4). Segments S4 are probably the voltage-sensors and are
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000305}.
CC -!- PTM: Phosphorylation at Ser-1341 by PKC in a highly conserved
CC cytoplasmic loop slows inactivation of the sodium channel and reduces
CC peak sodium currents. {ECO:0000250}.
CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 7 (HSAN7)
CC [MIM:615548]: A form of hereditary sensory and autonomic neuropathy, a
CC genetically and clinically heterogeneous group of disorders
CC characterized by degeneration of dorsal root and autonomic ganglion
CC cells, and by sensory and/or autonomic abnormalities. HSAN7 is
CC characterized by congenital inability to experience pain resulting in
CC self-mutilations, slow-healing wounds, and multiple painless fractures.
CC mild muscle weakness, delayed motor development, slightly reduced motor
CC and sensory nerve conduction velocities, hyperhidrosis and
CC gastrointestinal dysfunction. {ECO:0000269|PubMed:24036948,
CC ECO:0000269|PubMed:26645915}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Episodic pain syndrome, familial, 3 (FEPS3) [MIM:615552]: An
CC autosomal dominant neurologic disorder characterized by paroxysmal pain
CC mainly affecting the distal lower extremities and occasionally the
CC upper body, especially the joints of fingers and arms. The pain is
CC exacerbated with fatigue. {ECO:0000269|PubMed:24207120,
CC ECO:0000269|PubMed:24776970, ECO:0000269|PubMed:25791876,
CC ECO:0000269|PubMed:27224030}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.9/SCN11A subfamily. {ECO:0000305}.
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DR EMBL; AF188679; AAF17480.1; -; mRNA.
DR EMBL; AF109737; AAF24976.1; -; mRNA.
DR EMBL; AF150882; AAF24980.1; -; mRNA.
DR EMBL; AJ417790; CAD10507.1; -; mRNA.
DR EMBL; AC116038; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY686224; AAT95434.1; -; mRNA.
DR CCDS; CCDS33737.1; -. [Q9UI33-1]
DR RefSeq; NP_001274152.1; NM_001287223.1.
DR RefSeq; NP_054858.2; NM_014139.2. [Q9UI33-1]
DR RefSeq; XP_016861138.1; XM_017005649.1.
DR RefSeq; XP_016861139.1; XM_017005650.1. [Q9UI33-1]
DR AlphaFoldDB; Q9UI33; -.
DR SMR; Q9UI33; -.
DR BioGRID; 116436; 1.
DR IntAct; Q9UI33; 3.
DR STRING; 9606.ENSP00000307599; -.
DR BindingDB; Q9UI33; -.
DR ChEMBL; CHEMBL5167; -.
DR DrugBank; DB09088; Amylocaine.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB13269; Dichlorobenzyl alcohol.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB11186; Pentoxyverine.
DR DrugBank; DB09345; Pramocaine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB09342; Propoxycaine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB09085; Tetracaine.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; Q9UI33; -.
DR TCDB; 1.A.1.10.9; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q9UI33; 8 sites.
DR iPTMnet; Q9UI33; -.
DR PhosphoSitePlus; Q9UI33; -.
DR BioMuta; SCN11A; -.
DR DMDM; 124053649; -.
DR jPOST; Q9UI33; -.
DR MassIVE; Q9UI33; -.
DR PaxDb; Q9UI33; -.
DR PeptideAtlas; Q9UI33; -.
DR PRIDE; Q9UI33; -.
DR ProteomicsDB; 84461; -. [Q9UI33-1]
DR ProteomicsDB; 84462; -. [Q9UI33-2]
DR ProteomicsDB; 84463; -. [Q9UI33-3]
DR Antibodypedia; 28814; 121 antibodies from 24 providers.
DR DNASU; 11280; -.
DR Ensembl; ENST00000302328.9; ENSP00000307599.3; ENSG00000168356.13. [Q9UI33-1]
DR Ensembl; ENST00000444237.2; ENSP00000408028.2; ENSG00000168356.13. [Q9UI33-2]
DR Ensembl; ENST00000456224.7; ENSP00000416757.3; ENSG00000168356.13. [Q9UI33-3]
DR Ensembl; ENST00000668754.1; ENSP00000499569.1; ENSG00000168356.13. [Q9UI33-1]
DR GeneID; 11280; -.
DR KEGG; hsa:11280; -.
DR MANE-Select; ENST00000302328.9; ENSP00000307599.3; NM_001349253.2; NP_001336182.1.
DR UCSC; uc003cis.2; human. [Q9UI33-1]
DR CTD; 11280; -.
DR DisGeNET; 11280; -.
DR GeneCards; SCN11A; -.
DR GeneReviews; SCN11A; -.
DR HGNC; HGNC:10583; SCN11A.
DR HPA; ENSG00000168356; Tissue enhanced (lymphoid tissue, placenta).
DR MalaCards; SCN11A; -.
DR MIM; 604385; gene.
DR MIM; 615548; phenotype.
DR MIM; 615552; phenotype.
DR neXtProt; NX_Q9UI33; -.
DR OpenTargets; ENSG00000168356; -.
DR Orphanet; 88642; Congenital insensitivity to pain-anosmia-neuropathic arthropathy.
DR Orphanet; 391392; Familial episodic pain syndrome with predominantly lower limb involvement.
DR Orphanet; 391397; Hereditary sensory and autonomic neuropathy type 7.
DR Orphanet; 46348; Paroxysmal extreme pain disorder.
DR Orphanet; 90026; Primary erythromelalgia.
DR Orphanet; 306577; Sodium channelopathy-related small fiber neuropathy.
DR PharmGKB; PA35001; -.
DR VEuPathDB; HostDB:ENSG00000168356; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000161553; -.
DR HOGENOM; CLU_000540_5_0_1; -.
DR InParanoid; Q9UI33; -.
DR OMA; VEIDMFP; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q9UI33; -.
DR TreeFam; TF323985; -.
DR PathwayCommons; Q9UI33; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; Q9UI33; -.
DR SIGNOR; Q9UI33; -.
DR BioGRID-ORCS; 11280; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; SCN11A; human.
DR GeneWiki; Nav1.9; -.
DR GenomeRNAi; 11280; -.
DR Pharos; Q9UI33; Tclin.
DR PRO; PR:Q9UI33; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UI33; protein.
DR Bgee; ENSG00000168356; Expressed in buccal mucosa cell and 106 other tissues.
DR ExpressionAtlas; Q9UI33; baseline and differential.
DR Genevisible; Q9UI33; HS.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0044299; C:C-fiber; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IBA:GO_Central.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; TAS:ProtInc.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028821; Na_channel_a11su.
DR InterPro; IPR001696; Na_channel_asu.
DR InterPro; IPR044564; Na_chnl_inactivation_gate.
DR InterPro; IPR010526; Na_trans_assoc.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 1.
DR PANTHER; PTHR10037:SF210; PTHR10037:SF210; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR Pfam; PF06512; Na_trans_assoc; 1.
DR PRINTS; PR00170; NACHANNEL.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Neurodegeneration;
KW Neuropathy; Phosphoprotein; Reference proteome; Repeat; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..1791
FT /note="Sodium channel protein type 11 subunit alpha"
FT /id="PRO_0000048510"
FT TOPO_DOM 1..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 127..148
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 149..156
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 157..180
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 181..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 193..212
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 213..219
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 220..239
FT /note="Helical; Voltage-sensor; Name=S4 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 240..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 256..269
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 270..344
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 345..369
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 370..376
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 377..402
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250"
FT TOPO_DOM 403..572
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 573..596
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 597..607
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 608..631
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 632..639
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 640..659
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 660..667
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 668..687
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 688..702
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 703..725
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 726..753
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 754..774
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 775..785
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 786..811
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250"
FT TOPO_DOM 812..1051
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1052..1074
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1075..1088
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1089..1114
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1115..1120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1121..1138
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1139
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1140..1161
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1162..1180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1181..1202
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1203..1243
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1244..1265
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1266..1281
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1282..1308
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1309..1361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1362..1385
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1386..1396
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1397..1420
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1421..1426
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1427..1450
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1451..1461
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1462..1484
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1485..1499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1500..1522
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1523..1536
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1537..1559
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1560..1579
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1580..1604
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250"
FT TOPO_DOM 1605..1791
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 115..408
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 559..833
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1044..1339
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1348..1639
FT /note="IV"
FT /evidence="ECO:0000305"
FT MOD_RES 1341
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 283..322
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 776..787
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VAR_SEQ 946..983
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15302875"
FT /id="VSP_012259"
FT VAR_SEQ 1444
FT /note="T -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10623608"
FT /id="VSP_012260"
FT VAR_SEQ 1445..1791
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10623608"
FT /id="VSP_012261"
FT VARIANT 222
FT /note="R -> H (in FEPS3; dbSNP:rs1230622899)"
FT /evidence="ECO:0000269|PubMed:27224030"
FT /id="VAR_076679"
FT VARIANT 222
FT /note="R -> S (in FEPS3)"
FT /evidence="ECO:0000269|PubMed:27224030"
FT /id="VAR_076680"
FT VARIANT 225
FT /note="R -> C (in FEPS3; dbSNP:rs138607170)"
FT /evidence="ECO:0000269|PubMed:24207120"
FT /id="VAR_070919"
FT VARIANT 308
FT /note="P -> L (in dbSNP:rs751477540)"
FT /evidence="ECO:0000269|PubMed:27224030"
FT /id="VAR_076681"
FT VARIANT 381
FT /note="I -> T (in FEPS3; causes hyperexcitability of dorsal
FT root ganglion neurons; depolarizes resting membrane
FT potential; enhances spontaneous firing; hyperpolarizes
FT channel activation; slows deactivation; decreases rates of
FT current decay; does not change slow-inactivation;
FT dbSNP:rs606231280)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076682"
FT VARIANT 419
FT /note="K -> N (in dbSNP:rs150269814)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076683"
FT VARIANT 481
FT /note="G -> E (in dbSNP:rs13059805)"
FT /id="VAR_030002"
FT VARIANT 582
FT /note="A -> T (in dbSNP:rs141228634)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076684"
FT VARIANT 681
FT /note="A -> D"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076685"
FT VARIANT 699
FT /note="G -> R (in FEPS3; causes hyperexcitability of dorsal
FT root ganglion neurons; hyperpolarizes channel activation;
FT slows deactivation; depolarizes steady-state fast-
FT inactivation; dbSNP:rs145734191)"
FT /evidence="ECO:0000269|PubMed:25791876"
FT /id="VAR_076686"
FT VARIANT 777
FT /note="M -> R (in dbSNP:rs4302324)"
FT /id="VAR_030003"
FT VARIANT 808
FT /note="A -> G (in FEPS3; dbSNP:rs483352921)"
FT /evidence="ECO:0000269|PubMed:24207120"
FT /id="VAR_070920"
FT VARIANT 811
FT /note="L -> P (in HSAN7; results in excessive channel
FT activity at resting voltages; causes sustained
FT depolarization of nociceptors and impaired generation of
FT action potentials; causes aberrant synaptic transmission;
FT causes transient hyperexcitability of dorsal root ganglion
FT neurons; dbSNP:rs483352920)"
FT /evidence="ECO:0000269|PubMed:24036948,
FT ECO:0000269|PubMed:26645915"
FT /id="VAR_070921"
FT VARIANT 842
FT /note="A -> P (in dbSNP:rs1373209779)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076687"
FT VARIANT 909
FT /note="V -> I (in dbSNP:rs33985936)"
FT /evidence="ECO:0000269|PubMed:27224030"
FT /id="VAR_048697"
FT VARIANT 1158
FT /note="L -> P (in FEPS3; slows deactivation; depolarizes
FT resting membrane potential; enhances spontaneous firing;
FT decreases rates of current decay; does not change fast-
FT inactivation; does not change slow-inactivation;
FT dbSNP:rs141686175)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076688"
FT VARIANT 1184
FT /note="V -> A (in HSAN7; cold-aggravated peripheral pain
FT seen in some patients; enhances the channel activity by
FT shifting the voltage dependence of channel opening to
FT hyperpolarized potentials thereby giving rise to
FT hyperexcitability of nociceptors; causes hyperexcitability
FT and reduced cold-sensitivity of dorsal root ganglion
FT neurons)"
FT /evidence="ECO:0000269|PubMed:26645915"
FT /id="VAR_075250"
FT VARIANT 1198
FT /note="Y -> H (in dbSNP:rs12638601)"
FT /id="VAR_030004"
FT VARIANT 1609
FT /note="T -> I (in dbSNP:rs72869687)"
FT /evidence="ECO:0000269|PubMed:27224030"
FT /id="VAR_076689"
FT VARIANT 1689
FT /note="F -> L (in dbSNP:rs201107889)"
FT /evidence="ECO:0000269|PubMed:24776970"
FT /id="VAR_076690"
FT CONFLICT 576
FT /note="D -> G (in Ref. 3; CAD10507)"
FT /evidence="ECO:0000305"
FT CONFLICT 703
FT /note="S -> N (in Ref. 2; AAF24976/AAF24980)"
FT /evidence="ECO:0000305"
FT CONFLICT 847
FT /note="R -> G (in Ref. 3; CAD10507)"
FT /evidence="ECO:0000305"
FT CONFLICT 1086
FT /note="I -> T (in Ref. 5; AAT95434)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1791 AA; 204922 MW; DE38680BFB639ED1 CRC64;
MDDRCYPVIF PDERNFRPFT SDSLAAIEKR IAIQKEKKKS KDQTGEVPQP RPQLDLKASR
KLPKLYGDIP RELIGKPLED LDPFYRNHKT FMVLNRKRTI YRFSAKHALF IFGPFNSIRS
LAIRVSVHSL FSMFIIGTVI INCVFMATGP AKNSNSNNTD IAECVFTGIY IFEALIKILA
RGFILDEFSF LRDPWNWLDS IVIGIAIVSY IPGITIKLLP LRTFRVFRAL KAISVVSRLK
VIVGALLRSV KKLVNVIILT FFCLSIFALV GQQLFMGSLN LKCISRDCKN ISNPEAYDHC
FEKKENSPEF KMCGIWMGNS ACSIQYECKH TKINPDYNYT NFDNFGWSFL AMFRLMTQDS
WEKLYQQTLR TTGLYSVFFF IVVIFLGSFY LINLTLAVVT MAYEEQNKNV AAEIEAKEKM
FQEAQQLLKE EKEALVAMGI DRSSLTSLET SYFTPKKRKL FGNKKRKSFF LRESGKDQPP
GSDSDEDCQK KPQLLEQTKR LSQNLSLDHF DEHGDPLQRQ RALSAVSILT ITMKEQEKSQ
EPCLPCGENL ASKYLVWNCC PQWLCVKKVL RTVMTDPFTE LAITICIIIN TVFLAMEHHK
MEASFEKMLN IGNLVFTSIF IAEMCLKIIA LDPYHYFRRG WNIFDSIVAL LSFADVMNCV
LQKRSWPFLR SFRVLRVFKL AKSWPTLNTL IKIIGNSVGA LGSLTVVLVI VIFIFSVVGM
QLFGRSFNSQ KSPKLCNPTG PTVSCLRHWH MGDFWHSFLV VFRILCGEWI ENMWECMQEA
NASSSLCVIV FILITVIGKL VVLNLFIALL LNSFSNEERN GNLEGEARKT KVQLALDRFR
RAFCFVRHTL EHFCHKWCRK QNLPQQKEVA GGCAAQSKDI IPLVMEMKRG SETQEELGIL
TSVPKTLGVR HDWTWLAPLA EEEDDVEFSG EDNAQRITQP EPEQQAYELH QENKKPTSQR
VQSVEIDMFS EDEPHLTIQD PRKKSDVTSI LSECSTIDLQ DGFGWLPEMV PKKQPERCLP
KGFGCCFPCC SVDKRKPPWV IWWNLRKTCY QIVKHSWFES FIIFVILLSS GALIFEDVHL
ENQPKIQELL NCTDIIFTHI FILEMVLKWV AFGFGKYFTS AWCCLDFIIV IVSVTTLINL
MELKSFRTLR ALRPLRALSQ FEGMKVVVNA LIGAIPAILN VLLVCLIFWL VFCILGVYFF
SGKFGKCING TDSVINYTII TNKSQCESGN FSWINQKVNF DNVGNAYLAL LQVATFKGWM
DIIYAAVDST EKEQQPEFES NSLGYIYFVV FIIFGSFFTL NLFIGVIIDN FNQQQKKLGG
QDIFMTEEQK KYYNAMKKLG SKKPQKPIPR PLNKCQGLVF DIVTSQIFDI IIISLIILNM
ISMMAESYNQ PKAMKSILDH LNWVFVVIFT LECLIKIFAL RQYYFTNGWN LFDCVVVLLS
IVSTMISTLE NQEHIPFPPT LFRIVRLARI GRILRLVRAA RGIRTLLFAL MMSLPSLFNI
GLLLFLIMFI YAILGMNWFS KVNPESGIDD IFNFKTFASS MLCLFQISTS AGWDSLLSPM
LRSKESCNSS SENCHLPGIA TSYFVSYIII SFLIVVNMYI AVILENFNTA TEESEDPLGE
DDFDIFYEVW EKFDPEATQF IKYSALSDFA DALPEPLRVA KPNKYQFLVM DLPMVSEDRL
HCMDILFAFT ARVLGGSDGL DSMKAMMEEK FMEANPLKKL YEPIVTTTKR KEEERGAAII
QKAFRKYMMK VTKGDQGDQN DLENGPHSPL QTLCNGDLSS FGVAKGKVHC D
