SCNAA_HUMAN
ID SCNAA_HUMAN Reviewed; 1956 AA.
AC Q9Y5Y9; A6NDQ1;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Sodium channel protein type 10 subunit alpha;
DE AltName: Full=Peripheral nerve sodium channel 3;
DE Short=PN3;
DE Short=hPN3;
DE AltName: Full=Sodium channel protein type X subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.8;
GN Name=SCN10A;
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], FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION,
RP TISSUE SPECIFICITY, AND VARIANTS ALA-1073 AND VAL-1713.
RC TISSUE=Spinal ganglion;
RX PubMed=9839820; DOI=10.1016/s0304-3959(98)00120-1;
RA Rabert D.K., Koch B.D., Ilnicka M., Obernolte R.A., Naylor S.L.,
RA Herman R.C., Eglen R.M., Hunter J.C., Sangameswaran L.;
RT "A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal
RT root ganglia, hPN3/SCN10A.";
RL Pain 78:107-114(1998).
RN [2]
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 [3]
RP VARIANT TRP-916.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
RN [4]
RP VARIANTS FEPS2 PRO-554 AND THR-1304, CHARACTERIZATION OF VARIANTS FEPS2
RP PRO-554 AND THR-1304, VARIANTS LEU-939; LEU-940; ASN-1056; TYR-1523 AND
RP SER-1662, AND CHARACTERIZATION OF VARIANT TYR-1523.
RX PubMed=23115331; DOI=10.1073/pnas.1216080109;
RA Faber C.G., Lauria G., Merkies I.S., Cheng X., Han C., Ahn H.S.,
RA Persson A.K., Hoeijmakers J.G., Gerrits M.M., Pierro T., Lombardi R.,
RA Kapetis D., Dib-Hajj S.D., Waxman S.G.;
RT "Gain-of-function Nav1.8 mutations in painful neuropathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19444-19449(2012).
CC -!- FUNCTION: Tetrodotoxin-resistant channel that mediates the voltage-
CC dependent sodium ion permeability of excitable membranes. Assuming
CC opened or closed conformations in response to the voltage difference
CC across the membrane, the protein forms a sodium-selective channel
CC through which sodium ions may pass in accordance with their
CC electrochemical gradient. Plays a role in neuropathic pain mechanisms.
CC {ECO:0000269|PubMed:9839820}.
CC -!- SUBUNIT: The channel consists of an ion conducting pore forming alpha-
CC subunit regulated by one or more associated auxiliary subunits SCN1B,
CC SCN2B and SCN3B; electrophysiological properties may vary depending on
CC the type of the associated beta subunits. Found in a number of
CC complexes with PRX, DYNLT1 and PDZD2. Interacts with proteins such as
CC FSTL1, PRX, DYNLT1, PDZD2, S100A10 and many others (By similarity).
CC Interacts with NEDD4 and NEDD4L. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:D0E0C2};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Note=It can
CC be translocated to the cell membrane through association with S100A10.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the dorsal root ganglia and sciatic
CC nerve. {ECO:0000269|PubMed:9839820}.
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: Ubiquitinated by NEDD4L; which promotes its endocytosis.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-1451 by PKC in a highly conserved
CC cytoplasmic loop slows inactivation of the sodium channel and reduces
CC peak sodium currents. {ECO:0000250}.
CC -!- PTM: Lacks the cysteine which covalently binds the conotoxin GVIIJ.
CC This cysteine (position 816) is speculated in other sodium channel
CC subunits alpha to be implied in covalent binding with the sodium
CC channel subunit beta-2 or beta-4. {ECO:0000250|UniProtKB:P15389}.
CC -!- DISEASE: Episodic pain syndrome, familial, 2 (FEPS2) [MIM:615551]: An
CC autosomal dominant neurologic disorder characterized by adult-onset of
CC paroxysmal pain mainly affecting the distal lower extremities.
CC {ECO:0000269|PubMed:23115331}. 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 Nav1.8/SCN10A subfamily. {ECO:0000305}.
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DR EMBL; AF117907; AAD30863.1; -; mRNA.
DR EMBL; AC116038; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137625; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33736.1; -.
DR RefSeq; NP_001280235.2; NM_001293306.2.
DR RefSeq; NP_001280236.2; NM_001293307.2.
DR RefSeq; NP_006505.3; NM_006514.3.
DR AlphaFoldDB; Q9Y5Y9; -.
DR SMR; Q9Y5Y9; -.
DR IntAct; Q9Y5Y9; 3.
DR STRING; 9606.ENSP00000390600; -.
DR BindingDB; Q9Y5Y9; -.
DR ChEMBL; CHEMBL5451; -.
DR DrugBank; DB09088; Amylocaine.
DR DrugBank; DB01086; Benzocaine.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB00297; Bupivacaine.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB01161; Chloroprocaine.
DR DrugBank; DB00527; Cinchocaine.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB13269; Dichlorobenzyl alcohol.
DR DrugBank; DB00645; Dyclonine.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00473; Hexylcaine.
DR DrugBank; DB06218; Lacosamide.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB01002; Levobupivacaine.
DR DrugBank; DB00281; Lidocaine.
DR DrugBank; DB00961; Mepivacaine.
DR DrugBank; DB01173; Orphenadrine.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB00892; Oxybuprocaine.
DR DrugBank; DB11186; Pentoxyverine.
DR DrugBank; DB09345; Pramocaine.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB00807; Proparacaine.
DR DrugBank; DB09342; Propoxycaine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00296; Ropivacaine.
DR DrugBank; DB09085; Tetracaine.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB00313; Valproic acid.
DR DrugCentral; Q9Y5Y9; -.
DR GuidetoPHARMACOLOGY; 585; -.
DR GlyGen; Q9Y5Y9; 9 sites.
DR iPTMnet; Q9Y5Y9; -.
DR PhosphoSitePlus; Q9Y5Y9; -.
DR BioMuta; SCN10A; -.
DR DMDM; 205371821; -.
DR MassIVE; Q9Y5Y9; -.
DR PaxDb; Q9Y5Y9; -.
DR PeptideAtlas; Q9Y5Y9; -.
DR PRIDE; Q9Y5Y9; -.
DR ProteomicsDB; 86545; -.
DR ABCD; Q9Y5Y9; 1 sequenced antibody.
DR Antibodypedia; 28790; 242 antibodies from 29 providers.
DR DNASU; 6336; -.
DR Ensembl; ENST00000449082.3; ENSP00000390600.2; ENSG00000185313.9.
DR GeneID; 6336; -.
DR KEGG; hsa:6336; -.
DR MANE-Select; ENST00000449082.3; ENSP00000390600.2; NM_006514.4; NP_006505.4.
DR UCSC; uc003ciq.4; human.
DR CTD; 6336; -.
DR DisGeNET; 6336; -.
DR GeneCards; SCN10A; -.
DR GeneReviews; SCN10A; -.
DR HGNC; HGNC:10582; SCN10A.
DR HPA; ENSG00000185313; Not detected.
DR MalaCards; SCN10A; -.
DR MIM; 604427; gene.
DR MIM; 615551; phenotype.
DR neXtProt; NX_Q9Y5Y9; -.
DR OpenTargets; ENSG00000185313; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 88642; Congenital insensitivity to pain-anosmia-neuropathic arthropathy.
DR Orphanet; 46348; Paroxysmal extreme pain disorder.
DR Orphanet; 90026; Primary erythromelalgia.
DR Orphanet; 101016; Romano-Ward syndrome.
DR Orphanet; 306577; Sodium channelopathy-related small fiber neuropathy.
DR PharmGKB; PA35000; -.
DR VEuPathDB; HostDB:ENSG00000185313; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000154992; -.
DR HOGENOM; CLU_000540_5_0_1; -.
DR InParanoid; Q9Y5Y9; -.
DR OMA; CCKVDTT; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q9Y5Y9; -.
DR TreeFam; TF323985; -.
DR PathwayCommons; Q9Y5Y9; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; Q9Y5Y9; -.
DR SIGNOR; Q9Y5Y9; -.
DR BioGRID-ORCS; 6336; 10 hits in 1068 CRISPR screens.
DR GeneWiki; SCN10A; -.
DR GenomeRNAi; 6336; -.
DR Pharos; Q9Y5Y9; Tclin.
DR PRO; PR:Q9Y5Y9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y5Y9; protein.
DR Bgee; ENSG00000185313; Expressed in pancreatic ductal cell and 17 other tissues.
DR ExpressionAtlas; Q9Y5Y9; baseline and differential.
DR Genevisible; Q9Y5Y9; HS.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0071439; C:clathrin complex; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:BHF-UCL.
DR GO; GO:0086016; P:AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086043; P:bundle of His cell action potential; IMP:BHF-UCL.
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:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0007600; P:sensory perception; TAS:ProtInc.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028809; Na_channel_a10su.
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:SF208; PTHR10037:SF208; 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 Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..1956
FT /note="Sodium channel protein type 10 subunit alpha"
FT /id="PRO_0000048507"
FT TOPO_DOM 1..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 126..149
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..154
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 155..174
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..187
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 188..206
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..212
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 213..232
FT /note="Helical; Voltage-sensor; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..248
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 249..272
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..341
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 342..366
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 367..373
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 374..399
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..659
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 660..684
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 685..695
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 696..719
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 720..727
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 728..747
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 748..753
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 754..773
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 774..789
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 790..810
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 811..834
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 835..855
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 856..864
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 865..890
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 891..1147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1148..1171
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1172..1184
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1185..1210
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1211..1216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1217..1238
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1239..1242
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1243..1264
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1265..1283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1284..1311
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1312..1353
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1354..1375
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1376..1391
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1392..1418
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1419..1471
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1472..1495
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1496..1506
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1507..1530
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1531..1536
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1537..1560
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1561..1572
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1573..1594
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1595..1609
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1610..1632
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1633..1646
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1647..1669
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1670..1697
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1698..1722
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1723..1956
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 116..405
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 647..911
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1140..1449
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1458..1757
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1851..1880
FT /note="IQ"
FT REGION 27..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..986
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1041..1089
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1909..1956
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..54
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..480
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1909..1946
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 1451
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 819
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 276..319
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 857..866
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VARIANT 509
FT /note="S -> P (in dbSNP:rs7630989)"
FT /id="VAR_020605"
FT VARIANT 554
FT /note="L -> P (in FEPS2; increases the excitability of
FT small DRG neurons; dbSNP:rs138404783)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070878"
FT VARIANT 590
FT /note="G -> R (in dbSNP:rs35332705)"
FT /id="VAR_048696"
FT VARIANT 916
FT /note="R -> W (found in a renal cell carcinoma sample;
FT somatic mutation; dbSNP:rs370208223)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064748"
FT VARIANT 939
FT /note="P -> L (in dbSNP:rs202174472)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070879"
FT VARIANT 940
FT /note="Q -> L"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070880"
FT VARIANT 1056
FT /note="D -> N (in dbSNP:rs751574392)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070881"
FT VARIANT 1073
FT /note="V -> A (in dbSNP:rs6795970)"
FT /evidence="ECO:0000269|PubMed:9839820"
FT /id="VAR_020606"
FT VARIANT 1092
FT /note="L -> P (in dbSNP:rs12632942)"
FT /id="VAR_020607"
FT VARIANT 1304
FT /note="A -> T (in FEPS2; increases the excitability of
FT small DRG neurons; dbSNP:rs142173735)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070882"
FT VARIANT 1523
FT /note="C -> Y (no gain in function in response to
FT depolarization; dbSNP:rs142217269)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070883"
FT VARIANT 1662
FT /note="G -> S (in dbSNP:rs151090729)"
FT /evidence="ECO:0000269|PubMed:23115331"
FT /id="VAR_070884"
FT VARIANT 1713
FT /note="M -> V (in dbSNP:rs6599241)"
FT /evidence="ECO:0000269|PubMed:9839820"
FT /id="VAR_020608"
SQ SEQUENCE 1956 AA; 220626 MW; 4A4A2C5E135B6685 CRC64;
MEFPIGSLET NNFRRFTPES LVEIEKQIAA KQGTKKAREK HREQKDQEEK PRPQLDLKAC
NQLPKFYGEL PAELIGEPLE DLDPFYSTHR TFMVLNKGRT ISRFSATRAL WLFSPFNLIR
RTAIKVSVHS WFSLFITVTI LVNCVCMTRT DLPEKIEYVF TVIYTFEALI KILARGFCLN
EFTYLRDPWN WLDFSVITLA YVGTAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI
HSVKKLADVT ILTIFCLSVF ALVGLQLFKG NLKNKCVKND MAVNETTNYS SHRKPDIYIN
KRGTSDPLLC GNGSDSGHCP DGYICLKTSD NPDFNYTSFD SFAWAFLSLF RLMTQDSWER
LYQQTLRTSG KIYMIFFVLV IFLGSFYLVN LILAVVTMAY EEQNQATTDE IEAKEKKFQE
ALEMLRKEQE VLAALGIDTT SLHSHNGSPL TSKNASERRH RIKPRVSEGS TEDNKSPRSD
PYNQRRMSFL GLASGKRRAS HGSVFHFRSP GRDISLPEGV TDDGVFPGDH ESHRGSLLLG
GGAGQQGPLP RSPLPQPSNP DSRHGEDEHQ PPPTSELAPG AVDVSAFDAG QKKTFLSAEY
LDEPFRAQRA MSVVSIITSV LEELEESEQK CPPCLTSLSQ KYLIWDCCPM WVKLKTILFG
LVTDPFAELT ITLCIVVNTI FMAMEHHGMS PTFEAMLQIG NIVFTIFFTA EMVFKIIAFD
PYYYFQKKWN IFDCIIVTVS LLELGVAKKG SLSVLRSFRL LRVFKLAKSW PTLNTLIKII
GNSVGALGNL TIILAIIVFV FALVGKQLLG ENYRNNRKNI SAPHEDWPRW HMHDFFHSFL
IVFRILCGEW IENMWACMEV GQKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA
PEDDGEVNNL QVALARIQVF GHRTKQALCS FFSRSCPFPQ PKAEPELVVK LPLSSSKAEN
HIAANTARGS SGGLQAPRGP RDEHSDFIAN PTVWVSVPIA EGESDLDDLE DDGGEDAQSF
QQEVIPKGQQ EQLQQVERCG DHLTPRSPGT GTSSEDLAPS LGETWKDESV PQVPAEGVDD
TSSSEGSTVD CLDPEEILRK IPELADDLEE PDDCFTEGCI RHCPCCKLDT TKSPWDVGWQ
VRKTCYRIVE HSWFESFIIF MILLSSGSLA FEDYYLDQKP TVKALLEYTD RVFTFIFVFE
MLLKWVAYGF KKYFTNAWCW LDFLIVNISL ISLTAKILEY SEVAPIKALR TLRALRPLRA
LSRFEGMRVV VDALVGAIPS IMNVLLVCLI FWLIFSIMGV NLFAGKFWRC INYTDGEFSL
VPLSIVNNKS DCKIQNSTGS FFWVNVKVNF DNVAMGYLAL LQVATFKGWM DIMYAAVDSR
EVNMQPKWED NVYMYLYFVI FIIFGGFFTL NLFVGVIIDN FNQQKKKLGG QDIFMTEEQK
KYYNAMKKLG SKKPQKPIPR PLNKFQGFVF DIVTRQAFDI TIMVLICLNM ITMMVETDDQ
SEEKTKILGK INQFFVAVFT GECVMKMFAL RQYYFTNGWN VFDFIVVVLS IASLIFSAIL
KSLQSYFSPT LFRVIRLARI GRILRLIRAA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI
YSIFGMSSFP HVRWEAGIDD MFNFQTFANS MLCLFQITTS AGWDGLLSPI LNTGPPYCDP
NLPNSNGTRG DCGSPAVGII FFTTYIIISF LIMVNMYIAV ILENFNVATE ESTEPLSEDD
FDMFYETWEK FDPEATQFIT FSALSDFADT LSGPLRIPKP NRNILIQMDL PLVPGDKIHC
LDILFAFTKN VLGESGELDS LKANMEEKFM ATNLSKSSYE PIATTLRWKQ EDISATVIQK
AYRSYVLHRS MALSNTPCVP RAEEEAASLP DEGFVAFTAN ENCVLPDKSE TASATSFPPS
YESVTRGLSD RVNMRTSSSI QNEDEATSME LIAPGP
