SC4AA_TAKRU
ID SC4AA_TAKRU Reviewed; 1892 AA.
AC Q2XVR7;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 25-MAY-2022, entry version 84.
DE RecName: Full=Sodium channel protein type 4 subunit alpha A;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.4a;
GN Name=scn4aa; Synonyms=nav1.4a;
OS Takifugu rubripes (Japanese pufferfish) (Fugu rubripes).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Tetraodontiformes; Tetradontoidea; Tetraodontidae; Takifugu.
OX NCBI_TaxID=31033;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16303569; DOI=10.1016/j.cub.2005.10.068;
RA Venkatesh B., Lu S.Q., Dandona N., See S.L., Brenner S., Soong T.W.;
RT "Genetic basis of tetrodotoxin resistance in pufferfishes.";
RL Curr. Biol. 15:2069-2072(2005).
CC -!- FUNCTION: Pore-forming subunit of a voltage-gated sodium channel
CC complex through which Na(+) ions pass in accordance with their
CC electrochemical gradient. Alternates between resting, activated and
CC inactivated states. Required for normal muscle fiber excitability,
CC normal muscle contraction and relaxation cycles.
CC {ECO:0000250|UniProtKB:P35499}.
CC -!- ACTIVITY REGULATION: Channel activity is regulated by ancillary beta
CC subunits. Interaction with a beta subunit is required for rapid channel
CC inactivation and rapid recovery after inactivation, and prevents
CC decrease of channel activity in response to repetitive, high-frequency
CC depolarizations. {ECO:0000250|UniProtKB:P15390}.
CC -!- SUBUNIT: Component of a voltage-sensitive sodium channel complex that
CC consists of a pore-forming alpha subunit and one or more regulatory
CC beta subunits. {ECO:0000250|UniProtKB:P15390}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15390};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P35499}.
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:0000250|UniProtKB:P35499}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.4/SCN4A subfamily. {ECO:0000305}.
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DR EMBL; DQ221249; ABB29441.1; -; Genomic_DNA.
DR AlphaFoldDB; Q2XVR7; -.
DR SMR; Q2XVR7; -.
DR STRING; 31033.ENSTRUP00000005483; -.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; Q2XVR7; -.
DR Proteomes; UP000005226; Unplaced.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
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 Pfam; PF00520; Ion_trans; 4.
DR Pfam; PF06512; Na_trans_assoc; 1.
DR PRINTS; PR00170; NACHANNEL.
DR PROSITE; PS50096; IQ; 1.
PE 3: Inferred from homology;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Reference proteome; Repeat; Sodium; Sodium channel;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..1892
FT /note="Sodium channel protein type 4 subunit alpha A"
FT /id="PRO_0000371319"
FT TOPO_DOM 1..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 126..144
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 145..151
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 152..172
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 173..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 187..204
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 205..210
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 211..227
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 228..246
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 247..266
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 267..370
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 371..395
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 396..402
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 403..423
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 424..612
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 613..631
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 632..642
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 643..662
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 663..676
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 677..696
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 697..698
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 699..716
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 717..732
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 733..751
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 752..780
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 781..801
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 802..812
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 813..831
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 832..1071
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1072..1089
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1090..1102
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1103..1121
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1122..1135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1136..1154
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1155..1162
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1163..1181
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1182..1198
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1199..1218
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1219..1270
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1271..1292
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1293..1309
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1310..1331
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1332..1394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1395..1412
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1413..1423
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1424..1442
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1443..1454
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1455..1472
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1473..1485
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1486..1502
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1503..1521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1522..1539
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1540..1561
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1562..1584
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1585..1614
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1615..1637
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1638..1892
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 107..433
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 594..866
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1052..1366
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1375..1673
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1767..1796
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 34..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 884..905
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 945..982
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1350..1352
FT /note="Important for rapid channel inactivation"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT REGION 1836..1856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 885..905
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 950..968
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
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 1244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 274..339
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 348..354
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 765..771
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 803..812
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 1228..1248
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 1593..1608
FT /evidence="ECO:0000250|UniProtKB:P35499"
SQ SEQUENCE 1892 AA; 213099 MW; 36BDBC159AE3172C CRC64;
MATILPPPGT ALFRHFTRQS LATIERLKEE TLIAPKAGAH EEEEPPTPNP DLEAGKSLPM
IFGDPPSELL GTPLEDIDPF YKAQKTFVVV TKGNTIYRFN AEPACYILSP FSLVRRGAIK
ILIHSLFSTL IMITILSNCV FMTMSNPPAW SKTVEYVFTG IYTFEATVKV LSRGFCVGPF
TFLRDPWNWL DFMVISMAYI TEFVDLGNVS ALRTFRVLRA LKTITVIPGL KTIVAALIQS
VKKMVDVMIL TVFALAVFAL VGLQLFMGNL RHKCIRWPIA NETASELFNG TVFNDTLSYN
DTTWLNDTLD SNSTFDFTEY IENAENQYFL EGSKDALLCG NSTDAGKCPE GYLCMKAGRN
PNYGYTSFDS FGWAFLALFR LMTQDNWESL FQLTLRAAGQ TYMLFFVVVI FLGSFYLINL
ILAVVAMAYD EQNQASQQEA KEKEEEFQRL LEQLKNQEQA QVLGSRASLT SKKSVSLTGS
DVADDEQSLE NNEALKDCNG RPIPRLIIRA PTMKESAADY ELREKEESSV HSVLHLDEPG
LRERSASVAT AAASVATAAA SVATAAAMEE LEEAQRPCPP IWYRFADIFL KWNCCEKWVV
FKKWVHFVVM DPFVDLAITI CIVLNTLFMA MEHYPMTEEF DYMLSVGNLV FTGIFAAEMF
FKLIAMDPYY YFQVGWNIFD SIIVTLSLVE LGLANVQGLS VLRSFRLLRV FKLAKSWPTL
NMLIKIIGNS VGALGNLTLV LAIIVFIFAV VGMQLFGKSY KDCVCKISSD CELPRWHMND
FFHSFLIVFR ILCGEWIETM WDCMEVAGAG MCLVVFMMVM VIGNLVVLNL FLALLLSSFS
GDNLSVGDDD GELNNLQIAI GRITRGGNWL KAFLIGTVQR VLGREPQKPA EEDPADEGEG
KTEGMEMNHL DGFKLADGIA NCLVGGQPSG VTLDGESSIT VPIALGESDS ENPSEDDDDQ
EDDVDSEVTC EENEHHSDGV EDEFGVLQHV KLMGALTDGD SSVCSTVDYQ PPEPEVQEEE
EEEPDLVEPE ACFTDNCVKR WPCLNVDISQ GKGKKWWNLR KTCFTIVEHD WFETFIIFMI
LLSSGALAFE DIYIERRRTV KIVLEFADKV FTFIFVIEML LKWVAYGFKT YFTNAWCWLD
FFIVDISLIS LSANLMGFSD LGPIKSLRTL RALRPLRALS RFEGMRVVVN ALIGAIPSIF
NVLLVCLIFW LIFSIMGVNL FAGKFYRCIN TTTAELFPIS VVNNKSDCVA LQEATQEARW
VNVKVNYDNV AKGYLSLLQI ATFKGWMDIM YPAVDSREVE EQPSYEINLY MYIYFVIFII
FGSFFTLNLF IGVIIDNFNQ QKKKLGDKDI FMTEEQKKYY EAMKKLGSKK PQKPIPRPAN
LIQGLVFDFI SQQFFDIFIM VLICLNMVTM MVETDDQSPA KEDFLFKVNV AFIVVFTGEC
TLKLFALRHY FFTNGWNIFD FIVVILSIAG TMLSDIIEKY FVSPTLFRVI RLARIGRILR
LIKGARGIRT LLFALMMSLP ALFNIGLLLF LIMFIFSIFG MSNFAYVKKE AGINDMFNFE
TFGSSIICLF QITTSAGWDT LLLPMLNKEP PDCDPAFENP GTDVKGNCGN PMMGMVFFCS
YIIISFLVVV NMYIAIILEN FNVAQEESGD VLCEEDFEMF NETWEKFDTG GTQFIEYSQL
SDFCDALQEP LRVAKPNRQR LIEMDLPLVI GDRIHCVDVL LAVTQEVLGD TIEMVAMRES
IEAKFNLNNP TSASYAPITT TVRQKEEDMA AVVIQRAYRN HLHKRGIHHA AYIQRSKTGR
KAASEDAPEK EGLLAKKMGA LYGSDADLAD EVEGLRRRPD PQTRCSGARC SPEPPEPNII
LVPVEITNEL LLHSAPSQQS SPTQTILRET NV
