ID KCNC3_HUMAN Reviewed; 757 AA. AC Q14003; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 04-NOV-2008, sequence version 3. DT 24-JAN-2024, entry version 201. DE RecName: Full=Potassium voltage-gated channel subfamily C member 3; DE AltName: Full=KSHIIID; DE AltName: Full=Voltage-gated potassium channel subunit Kv3.3; GN Name=KCNC3; 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], VARIANT GLY-63, FUNCTION, AND SUBCELLULAR RP LOCATION. RC TISSUE=Lens epithelium; RX PubMed=10712820; DOI=10.1006/exer.1999.0796; RA Rae J.L., Shepard A.R.; RT "Kv3.3 potassium channels in lens epithelium and corneal endothelium."; RL Exp. Eye Res. 70:339-348(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 291-651. RA Lee J.E., Garbutt J.H., Phillips K.L., Roses A.D.; RT "A human chromosome 19 Shaw type potassium channel gene."; RL Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HAX1 AND ACTR3, AND RP DOMAIN. RX PubMed=26997484; DOI=10.1016/j.cell.2016.02.009; RA Zhang Y., Zhang X.F., Fleming M.R., Amiri A., El-Hassar L., Surguchev A.A., RA Hyland C., Jenkins D.P., Desai R., Brown M.R., Gazula V.R., Waters M.F., RA Large C.H., Horvath T.L., Navaratnam D., Vaccarino F.M., Forscher P., RA Kaczmarek L.K.; RT "Kv3.3 channels bind Hax-1 and Arp2/3 to assemble a stable local actin RT network that regulates channel gating."; RL Cell 165:434-448(2016). RN [5] RP CHARACTERIZATION OF VARIANTS SCA13 HIS-420; HIS-423 AND LEU-448, FUNCTION, RP AND SUBCELLULAR LOCATION. RX PubMed=22289912; DOI=10.1113/jphysiol.2012.228205; RA Minassian N.A., Lin M.C., Papazian D.M.; RT "Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type RT 13."; RL J. Physiol. (Lond.) 590:1599-1614(2012). RN [6] RP CHARACTERIZATION OF VARIANTS SCA13 HIS-366; HIS-420; HIS-423 AND LEU-448, RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH KCNC1, AND RP MUTAGENESIS OF ARG-366; ARG-420 AND ARG-423. RX PubMed=23734863; DOI=10.1042/bj20130034; RA Zhao J., Zhu J., Thornhill W.B.; RT "Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine RT mutations affect both functional and protein expression on the cell RT surface."; RL Biochem. J. 454:259-265(2013). RN [7] RP CHARACTERIZATION OF VARIANTS SCA13 HIS-420 AND LEU-448, SUBCELLULAR RP LOCATION, AND GLYCOSYLATION. RX PubMed=25152487; DOI=10.1016/j.nbd.2014.08.020; RA Gallego-Iradi C., Bickford J.S., Khare S., Hall A., Nick J.A., RA Salmasinia D., Wawrowsky K., Bannykh S., Huynh D.P., Rincon-Limas D.E., RA Pulst S.M., Nick H.S., Fernandez-Funez P., Waters M.F.; RT "KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia RT 13 displays aberrant intracellular trafficking."; RL Neurobiol. Dis. 71:270-279(2014). RN [8] RP VARIANTS SCA13 HIS-420 AND LEU-448, CHARACTERIZATION OF VARIANTS SCA13 RP HIS-420 AND LEU-448, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16501573; DOI=10.1038/ng1758; RA Waters M.F., Minassian N.A., Stevanin G., Figueroa K.P., Bannister J.P.A., RA Nolte D., Mock A.F., Evidente V.G.H., Fee D.B., Mueller U., Duerr A., RA Brice A., Papazian D.M., Pulst S.M.; RT "Mutations in voltage-gated potassium channel KCNC3 cause degenerative and RT developmental nervous system phenotypes."; RL Nat. Genet. 38:447-451(2006). RN [9] RP VARIANTS SCA13 HIS-366; HIS-420 AND HIS-423, CHARACTERIZATION OF VARIANTS RP SCA13 HIS-366 AND HIS-423, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19953606; DOI=10.1002/humu.21165; RA Figueroa K.P., Minassian N.A., Stevanin G., Waters M., Garibyan V., RA Forlani S., Strzelczyk A., Buerk K., Brice A., Duerr A., Papazian D.M., RA Pulst S.M.; RT "KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial RT ataxia patients."; RL Hum. Mutat. 31:191-196(2010). RN [10] RP VARIANT SCA13 HIS-423, VARIANT ASP-263, CHARACTERIZATION OF VARIANT RP ASP-263, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21479265; DOI=10.1371/journal.pone.0017811; RA Figueroa K.P., Waters M.F., Garibyan V., Bird T.D., Gomez C.M., Ranum L.P., RA Minassian N.A., Papazian D.M., Pulst S.M.; RT "Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 RT (SCA13)."; RL PLoS ONE 6:E17811-E17811(2011). RN [11] RP VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591; RP SER-643; ARG-645 AND ASN-746, VARIANTS HIS-41 AND GLY-63, CHARACTERIZATION RP OF VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591; RP SER-643; ARG-645 AND ASN-746, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25756792; DOI=10.1371/journal.pone.0116599; RA Duarri A., Nibbeling E.A., Fokkens M.R., Meijer M., Boerrigter M., RA Verschuuren-Bemelmans C.C., Kremer B.P., van de Warrenburg B.P., RA Dooijes D., Boddeke E., Sinke R.J., Verbeek D.S.; RT "Functional analysis helps to define KCNC3 mutational spectrum in dutch RT ataxia cases."; RL PLoS ONE 10:E0116599-E0116599(2015). CC -!- FUNCTION: Voltage-gated potassium channel that plays an important role CC in the rapid repolarization of fast-firing brain neurons. The channel CC opens in response to the voltage difference across the membrane, CC forming a potassium-selective channel through which potassium ions pass CC in accordance with their electrochemical gradient. The channel displays CC rapid activation and inactivation kinetics (PubMed:10712820, CC PubMed:26997484, PubMed:22289912, PubMed:23734863, PubMed:16501573, CC PubMed:19953606, PubMed:21479265, PubMed:25756792). It plays a role in CC the regulation of the frequency, shape and duration of action CC potentials in Purkinje cells. Required for normal survival of CC cerebellar neurons, probably via its role in regulating the duration CC and frequency of action potentials that in turn regulate the activity CC of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (By CC similarity). Required for normal motor function (PubMed:23734863, CC PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792). CC Plays a role in the reorganization of the cortical actin cytoskeleton CC and the formation of actin veil structures in neuronal growth cones via CC its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484). CC {ECO:0000250|UniProtKB:Q63959, ECO:0000269|PubMed:10712820, CC ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606, CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25756792, CC ECO:0000269|PubMed:26997484}. CC -!- SUBUNIT: Homotetramer. Heterotetramer with KCNC1 (PubMed:23734863). CC Interacts (via C-terminus) with HAX1 (PubMed:26997484). Identified in a CC complex with ACTR3, a subunit of the Arp2/3 complex; this interaction CC is indirect and depends on the presence of HAX1 (PubMed:26997484). CC Interaction with HAX1 modulates channel gating (PubMed:26997484). CC {ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:26997484}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10712820, CC ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606, CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487, CC ECO:0000269|PubMed:25756792, ECO:0000269|PubMed:26997484}; Multi-pass CC membrane protein {ECO:0000255}. Presynaptic cell membrane CC {ECO:0000250|UniProtKB:Q63959}; Multi-pass membrane protein CC {ECO:0000255}. Perikaryon {ECO:0000250|UniProtKB:Q63959}. Cell CC projection, axon {ECO:0000250|UniProtKB:Q63959}. Cell projection, CC dendrite {ECO:0000250|UniProtKB:Q63959}. Cell projection, dendritic CC spine membrane {ECO:0000250|UniProtKB:Q01956}; Multi-pass membrane CC protein {ECO:0000255}. Cytoplasm, cell cortex CC {ECO:0000269|PubMed:26997484}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:26997484}. Note=Detected on Purkinje cell dendritic CC spines, positioned perisynaptically but also in extrasynaptic positions CC along the spine membranes (By similarity). Detected at presynaptic CC calices of Held (By similarity). Colocalizes with the cortical actin CC cytoskeleton and the Arp2/3 complex (PubMed:26997484). CC {ECO:0000250|UniProtKB:Q01956, ECO:0000250|UniProtKB:Q63959, CC ECO:0000269|PubMed:26997484}. CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is CC characterized by a series of positively charged amino acids at every CC third position. {ECO:0000305}. CC -!- DOMAIN: The cytoplasmic N-terminus mediates N-type inactivation. CC {ECO:0000269|PubMed:26997484}. CC -!- DOMAIN: The C-terminal cytoplasmic tail contributes to the regulation CC of channel inactivation and to the interaction with HAX1 and the Arp2/3 CC complex. {ECO:0000269|PubMed:26997484}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:25152487}. CC -!- DISEASE: Spinocerebellar ataxia 13 (SCA13) [MIM:605259]: CC Spinocerebellar ataxia is a clinically and genetically heterogeneous CC group of cerebellar disorders. Patients show progressive incoordination CC of gait and often poor coordination of hands, speech and eye movements, CC due to degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar CC ataxia (ADCA) characterized by slow progression and variable age at CC onset, ranging from childhood to late adulthood. Intellectual CC disability can be present in some patients. CC {ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606, CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487, CC ECO:0000269|PubMed:25756792}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the potassium channel family. C (Shaw) CC (TC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF055989; AAC24118.1; -; mRNA. DR EMBL; AC008655; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z11585; CAA77671.1; -; Genomic_DNA. DR CCDS; CCDS12793.1; -. DR PIR; S19552; S19552. DR RefSeq; NP_004968.2; NM_004977.2. DR RefSeq; XP_006723266.1; XM_006723203.2. DR RefSeq; XP_011525228.1; XM_011526926.1. DR AlphaFoldDB; Q14003; -. DR SMR; Q14003; -. DR BioGRID; 109950; 34. DR IntAct; Q14003; 1. DR STRING; 9606.ENSP00000434241; -. DR ChEMBL; CHEMBL2362996; -. DR DrugBank; DB06637; Dalfampridine. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01069; Promethazine. DR DrugCentral; Q14003; -. DR TCDB; 1.A.1.2.13; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; Q14003; 3 sites, No reported glycans. DR GlyGen; Q14003; 4 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q14003; -. DR PhosphoSitePlus; Q14003; -. DR BioMuta; KCNC3; -. DR DMDM; 212276500; -. DR jPOST; Q14003; -. DR MassIVE; Q14003; -. DR MaxQB; Q14003; -. DR PaxDb; 9606-ENSP00000434241; -. DR PeptideAtlas; Q14003; -. DR ProteomicsDB; 59785; -. DR ABCD; Q14003; 1 sequenced antibody. DR Antibodypedia; 18827; 319 antibodies from 30 providers. DR DNASU; 3748; -. DR Ensembl; ENST00000477616.2; ENSP00000434241.1; ENSG00000131398.15. DR GeneID; 3748; -. DR KEGG; hsa:3748; -. DR MANE-Select; ENST00000477616.2; ENSP00000434241.1; NM_004977.3; NP_004968.2. DR UCSC; uc002pru.1; human. DR AGR; HGNC:6235; -. DR CTD; 3748; -. DR DisGeNET; 3748; -. DR GeneCards; KCNC3; -. DR GeneReviews; KCNC3; -. DR HGNC; HGNC:6235; KCNC3. DR HPA; ENSG00000131398; Tissue enhanced (brain, thyroid gland). DR MalaCards; KCNC3; -. DR MIM; 176264; gene. DR MIM; 605259; phenotype. DR neXtProt; NX_Q14003; -. DR OpenTargets; ENSG00000131398; -. DR Orphanet; 98768; Spinocerebellar ataxia type 13. DR PharmGKB; PA30027; -. DR VEuPathDB; HostDB:ENSG00000131398; -. DR eggNOG; KOG3713; Eukaryota. DR GeneTree; ENSGT00940000163131; -. DR InParanoid; Q14003; -. DR OMA; MYIETIC; -. DR OrthoDB; 4847734at2759; -. DR PhylomeDB; Q14003; -. DR TreeFam; TF352511; -. DR PathwayCommons; Q14003; -. DR Reactome; R-HSA-1296072; Voltage gated Potassium channels. DR SignaLink; Q14003; -. DR SIGNOR; Q14003; -. DR BioGRID-ORCS; 3748; 128 hits in 1168 CRISPR screens. DR ChiTaRS; KCNC3; human. DR GeneWiki; KCNC3; -. DR GenomeRNAi; 3748; -. DR Pharos; Q14003; Tclin. DR PRO; PR:Q14003; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q14003; Protein. DR Bgee; ENSG00000131398; Expressed in kidney epithelium and 148 other cell types or tissues. DR ExpressionAtlas; Q14003; baseline and differential. DR GO; GO:0043679; C:axon terminus; IBA:GO_Central. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central. DR GO; GO:0032591; C:dendritic spine membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central. DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB. DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB. DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB. DR CDD; cd18414; BTB_KCNC1_3; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR003968; K_chnl_volt-dep_Kv. DR InterPro; IPR003974; K_chnl_volt-dep_Kv3. DR InterPro; IPR005404; K_chnl_volt-dep_Kv3.3. DR InterPro; IPR021105; K_chnl_volt-dep_Kv3_ID. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR003131; T1-type_BTB. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR11537:SF184; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY C MEMBER 3; 1. DR PANTHER; PTHR11537; VOLTAGE-GATED POTASSIUM CHANNEL; 1. DR Pfam; PF02214; BTB_2; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF11404; Potassium_chann; 1. DR PRINTS; PR00169; KCHANNEL. DR PRINTS; PR01582; KV33CHANNEL. DR PRINTS; PR01491; KVCHANNEL. DR PRINTS; PR01498; SHAWCHANNEL. DR SMART; SM00225; BTB; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; Q14003; HS. PE 1: Evidence at protein level; KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Disease variant; KW Glycoprotein; Ion channel; Ion transport; Membrane; Methylation; KW Neurodegeneration; Phosphoprotein; Postsynaptic cell membrane; Potassium; KW Potassium channel; Potassium transport; Reference proteome; KW Spinocerebellar ataxia; Synapse; Transmembrane; Transmembrane helix; KW Transport; Voltage-gated channel. FT CHAIN 1..757 FT /note="Potassium voltage-gated channel subfamily C member FT 3" FT /id="PRO_0000054055" FT TOPO_DOM 1..290 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 291..309 FT /note="Helical; Name=Segment S1" FT /evidence="ECO:0000255" FT TRANSMEM 351..370 FT /note="Helical; Name=Segment S2" FT /evidence="ECO:0000255" FT TOPO_DOM 371..379 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 380..398 FT /note="Helical; Name=Segment S3" FT /evidence="ECO:0000255" FT TRANSMEM 412..434 FT /note="Helical; Voltage-sensor; Name=Segment S4" FT /evidence="ECO:0000255" FT TOPO_DOM 435..447 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 448..469 FT /note="Helical; Name=Segment S5" FT /evidence="ECO:0000255" FT TRANSMEM 518..539 FT /note="Helical; Name=Segment S6" FT /evidence="ECO:0000255" FT TOPO_DOM 540..757 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 1..87 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1..78 FT /note="Important for normal N-type inactivation" FT /evidence="ECO:0000269|PubMed:26997484" FT REGION 210..232 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 556..613 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 682..746 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 503..508 FT /note="Selectivity filter" FT /evidence="ECO:0000250" FT COMPBIAS 1..16 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 20..63 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 565..604 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 625 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q63959" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63959" FT MOD_RES 691 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63959" FT CARBOHYD 320 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 336 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 483 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 41 FT /note="Q -> H (in dbSNP:rs185017345)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074192" FT VARIANT 63 FT /note="D -> G (in dbSNP:rs375912738)" FT /evidence="ECO:0000269|PubMed:10712820, FT ECO:0000269|PubMed:25756792" FT /id="VAR_074193" FT VARIANT 129 FT /note="D -> N (in SCA13; uncertain significance; changes FT channel activity; shifts the voltage dependence of FT activation)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074194" FT VARIANT 263 FT /note="G -> D (changes channel activity; activates more FT quickly and deactivates more slowly)" FT /evidence="ECO:0000269|PubMed:21479265" FT /id="VAR_074195" FT VARIANT 366 FT /note="R -> H (in SCA13; uncertain significance; dominant FT negative that decreases channel activity; decreases protein FT abundance; decreases protein stability; decreases FT localization to the plasma membrane; no effect on FT tetramerization; dbSNP:rs769502387)" FT /evidence="ECO:0000269|PubMed:19953606, FT ECO:0000269|PubMed:23734863" FT /id="VAR_074196" FT VARIANT 420 FT /note="R -> H (in SCA13; dominant negative that induces FT loss of channel activity; decreases protein abundance; FT decreases protein stability; decreases localization to the FT plasma membrane and alters the localization of the FT wild-type protein; impairs N-glycosylation; no effect on FT tetramerization; dbSNP:rs104894699)" FT /evidence="ECO:0000269|PubMed:16501573, FT ECO:0000269|PubMed:19953606, ECO:0000269|PubMed:22289912, FT ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487, FT ECO:0000269|PubMed:25756792" FT /id="VAR_029530" FT VARIANT 423 FT /note="R -> H (in SCA13; dominant negative that reduces FT channel activity; alters gating; decreases protein FT abundance; decreases localization to the plasma membrane; FT no effect on tetramerization; dbSNP:rs797044872)" FT /evidence="ECO:0000269|PubMed:19953606, FT ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, FT ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25756792" FT /id="VAR_074197" FT VARIANT 448 FT /note="F -> L (in SCA13; alters gating; slows channel FT closing; decreases protein abundance; no effect on FT localization to the plasma membrane; no effect on FT N-glycosylation; no effect on tetramerization; FT dbSNP:rs104894700)" FT /evidence="ECO:0000269|PubMed:16501573, FT ECO:0000269|PubMed:22289912, ECO:0000269|PubMed:23734863, FT ECO:0000269|PubMed:25152487" FT /id="VAR_029531" FT VARIANT 477 FT /note="D -> N (in SCA13; uncertain significance; no effect FT on channel activity; dbSNP:rs148033381)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074198" FT VARIANT 535 FT /note="V -> M (in SCA13; changes channel activity; shifts FT the voltage dependence of activation)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074199" FT VARIANT 591 FT /note="S -> G (in SCA13; uncertain significance; reduces FT channel activity; shifts the voltage dependence of FT activation; dbSNP:rs549394447)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074200" FT VARIANT 643 FT /note="G -> S (in SCA13; uncertain significance; no effect FT on channel activity; dbSNP:rs778523009)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074201" FT VARIANT 645 FT /note="P -> R (in SCA13; uncertain significance; no effect FT on channel activity; dbSNP:rs1460306526)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074202" FT VARIANT 746 FT /note="D -> N (in SCA13; uncertain significance; no effect FT on channel activity; dbSNP:rs958323371)" FT /evidence="ECO:0000269|PubMed:25756792" FT /id="VAR_074203" FT MUTAGEN 1..78 FT /note="Missing: Loss of N-type inactivation." FT /evidence="ECO:0000269|PubMed:26997484" FT MUTAGEN 366 FT /note="R->K,A: Decreases protein abundance." FT /evidence="ECO:0000269|PubMed:23734863" FT MUTAGEN 420 FT /note="R->K,A: Decreases protein abundance." FT /evidence="ECO:0000269|PubMed:23734863" FT MUTAGEN 423 FT /note="R->K,A: Decreases protein abundance." FT /evidence="ECO:0000269|PubMed:23734863" FT MUTAGEN 592 FT /note="G->R: Loss of interaction with ACTR3. No effect on FT voltage-dependent channel opening or current amplitude, but FT decreased rate of inactivation during prolonged FT depolarization." FT /evidence="ECO:0000269|PubMed:26997484" SQ SEQUENCE 757 AA; 80578 MW; B44306B850DFD797 CRC64; MLSSVCVSSF RGRQGASKQQ PAPPPQPPES PPPPPLPPQQ QQPAQPGPAA SPAGPPAPRG PGDRRAEPCP GLPAAAMGRH GGGGGDSGKI VINVGGVRHE TYRSTLRTLP GTRLAGLTEP EAAARFDYDP GADEFFFDRH PGVFAYVLNY YRTGKLHCPA DVCGPLFEEE LGFWGIDETD VEACCWMTYR QHRDAEEALD SFEAPDPAGA ANAANAAGAH DGGLDDEAGA GGGGLDGAGG ELKRLCFQDA GGGAGGPPGG AGGAGGTWWR RWQPRVWALF EDPYSSRAAR YVAFASLFFI LISITTFCLE THEGFIHISN KTVTQASPIP GAPPENITNV EVETEPFLTY VEGVCVVWFT FEFLMRITFC PDKVEFLKSS LNIIDCVAIL PFYLEVGLSG LSSKAAKDVL GFLRVVRFVR ILRIFKLTRH FVGLRVLGHT LRASTNEFLL LIIFLALGVL IFATMIYYAE RIGADPDDIL GSNHTYFKNI PIGFWWAVVT MTTLGYGDMY PKTWSGMLVG ALCALAGVLT IAMPVPVIVN NFGMYYSLAM AKQKLPKKKN KHIPRPPQPG SPNYCKPDPP PPPPPHPHHG SGGISPPPPI TPPSMGVTVA GAYPAGPHTH PGLLRGGAGG LGIMGLPPLP APGEPCPLAQ EEVIEINRAD PRPNGDPAAA ALAHEDCPAI DQPAMSPEDK SPITPGSRGR YSRDRACFLL TDYAPSPDGS IRKATGAPPL PPQDWRKPGP PSFLPDLNAN AAAWISP //