SC4AA_DANRE
ID SC4AA_DANRE Reviewed; 1829 AA.
AC Q2XVR3; Q20JQ6;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 103.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=16830092; DOI=10.1007/s00239-005-0287-9;
RA Novak A.E., Jost M.C., Lu Y., Taylor A.D., Zakon H.H., Ribera A.B.;
RT "Gene duplications and evolution of vertebrate voltage-gated sodium
RT channels.";
RL J. Mol. Evol. 63:208-221(2006).
RN [2]
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 -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, brain, spinal cord,
CC and eye. {ECO:0000269|PubMed:16830092}.
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; DQ149506; ABA54921.1; -; mRNA.
DR EMBL; DQ221253; ABB29445.2; -; Genomic_DNA.
DR RefSeq; NP_001034914.1; NM_001039825.1.
DR AlphaFoldDB; Q2XVR3; -.
DR SMR; Q2XVR3; -.
DR STRING; 7955.ENSDARP00000097312; -.
DR PaxDb; Q2XVR3; -.
DR GeneID; 572442; -.
DR KEGG; dre:572442; -.
DR CTD; 572442; -.
DR ZFIN; ZDB-GENE-051201-2; scn4aa.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; Q2XVR3; -.
DR OrthoDB; 56920at2759; -.
DR PhylomeDB; Q2XVR3; -.
DR Reactome; R-DRE-5576892; Phase 0 - rapid depolarisation.
DR PRO; PR:Q2XVR3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
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: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:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
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 2: Evidence at transcript level;
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..1829
FT /note="Sodium channel protein type 4 subunit alpha A"
FT /id="PRO_0000371317"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 125..143
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 144..150
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 151..171
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 172..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..203
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 204..209
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 210..226
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 227..245
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 246..265
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 266..358
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 359..383
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 384..390
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..411
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 412..582
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 583..601
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 602..612
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 613..632
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 633..646
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 647..666
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 667..668
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 669..686
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 687..702
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 703..721
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 722..750
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 751..771
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 772..782
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 783..801
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 802..998
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 999..1016
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1017..1029
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1030..1048
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1049..1062
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1063..1081
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1082..1089
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1090..1108
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1109..1125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1126..1145
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1146..1196
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1197..1218
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1219..1235
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1236..1257
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1258..1320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1321..1338
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1339..1349
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1350..1368
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1369..1380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1381..1398
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1399..1411
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1412..1428
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1429..1447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1448..1465
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1466..1487
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1488..1510
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1511..1540
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1541..1563
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1564..1829
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 106..421
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 564..836
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 979..1292
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1301..1599
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1693..1722
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 32..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 901..957
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1276..1278
FT /note="Important for rapid channel inactivation"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT REGION 1765..1786
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 938..957
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 273..327
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 336..342
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 735..741
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 773..782
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 1155..1175
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 1519..1534
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT CONFLICT 310
FT /note="N -> S (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
FT CONFLICT 1054
FT /note="Missing (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
FT CONFLICT 1305
FT /note="Missing (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
FT CONFLICT 1721
FT /note="R -> Q (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
FT CONFLICT 1811
FT /note="I -> T (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
FT CONFLICT 1815
FT /note="L -> F (in Ref. 1; ABA54921)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1829 AA; 207737 MW; D68901979E1D5842 CRC64;
MARLLPPTGT SVFRRFTPES LVEIERLIQE KSTREELEGA EEEPQAPSSD LEAGKCLPMI
YGDPPGDLLN TPLEDIDPFY KTQKTFIVIS KGNTIFRFSS EPAMFCISPF SIVRRGAIKI
LIHSLFSMFI MITILSNCVF MTMSNPPAWS KTVEYVFTGI YTFEATVKVL SRGFCIGPFT
FLRDPWNWLD FMVISMAYVT EFVDLGNVSA LRTFRVLRAL KTITVIPGLK TIVGALIQSV
KKMIDVMILT IFALAVFALI GLQLFMGNLR QKCIRWPILN STIFDVYNSN MVNDTTLNVT
DTFDFKAYIN NEENQYFLEG SLDALLCGNS SDAGRCPEGY TCMKAGRNPN YGYTSYDNFG
WAFLALFRLM TQDFWENLFQ LTLRAAGKTY MIFFVVVIFL GSFYLINLIL AVVAMAYDEQ
NEATLAEARD KEEEFQRLLE QLKNQETGSK ASLASQKTQS RGSNRTGSLH DLADEDVIKD
CNGRIVPRLI VNRVSSNKEL SAEEDQKSLS SKHSMQYLDQ PKLSKRTASA LSVLTATMEG
LEDAQRPCPP GWYKFADMFL KWDCCAPWIL FKKWVHFVVM DPFVDLGITI CIVLNTLFMA
MEHYPMSPHF EHVLSVGNLV FTGIFTAEMV FKLIAMDPYY YFQVGWNIFD SIIVTLSLVE
LGLANVQGLS VLRSFRLLRV FKLAKSWPTL NMLIKIIGNS VGALGNLTLV LAIIVFIFAV
VGMQLFGKSY KDCVCKISED CELPRWHMND FFHSFLIVFR ILCGEWIETM WDCMEVAGAS
MCLIVFMMVM VIGNLVVLNL FLALLLSSFS GDNLSGGDDD GEMNNLQIAI GRITRGIDWV
KALVASMVQR ILGKKPDNTK EEGEGDIELY ALNHLDEGKM ADGLTNCLSP TLTVPIARCE
SDVEEDEDSE SSDEEDAKAT LNDGDSSVCS TVDYQPPEPE PEPEEVEEEE PEPEEPEACF
TEGCIRRCAC LSVDITEGWG KKWWNLRRTC FTIVEHDYFE TFIIFMILLS SGALAFEDIN
IERRRVIKTI LEYADKVFTY IFIVEMLLKW VAYGFKTYFT NAWCWLDFLI VDVSLVSLTA
NLMGYSELGA IKSLRTLRAL RPLRALSRFE GMRVVVNALV GAIPSIFNVL LVCLIFWLIF
SIMGVNLFAG KFYHCINTTT EERIPMDVVN NKSDCMALMY TNEVRWVNVK VNYDNVGLGY
LSLLQIATFK GWMDIMYAAV DSREVDEQPS YEINLYMYLY FVIFIIFGSF FTLNLFIGVI
IDNFNQQKSK FGGKDIFMTE EQKKYYNAMK KLGAKKRPKP IPRPSNIIQG LVFDFISKQF
FDIFIMVLIC LNMVTMMIET DDQSAEKEYV LYQINLVFIV VFTSECVLKL FALRQYFFTI
GWNVFDFVVV ILSIAGLMLS DIIEKYFVSP TLFRVIRLAR IGRVLRLIRG AKGIRTLLFA
LMMSLPALFN IGLLLFLIMF IFSIFGMSNF AYVKKQAGID DIFNFETFGG SIICLFEITT
SAGWDGLLLP ILNSGPPDCD PDFENPGTDV RGNCGNPGMG IMFFCSYIIM SFLVVVNMYI
AIILENFNNA QEESGDPLCE DDFDMFDETW EKFDVDATQF IEYDRLFDFV DALQEPLRIA
KPNRLKLISM DIPIVNGDKI HSQDILLAVT REVLGDTIEM DAMKESIEAK FIMNNPTSAS
FEPIITTLRR KEEERAAIAV QRIYRRHLLK RAIRYACFMR RSKRKVRNPN DNEPPETEGL
IARKMNTLYG SNPELAMALE LETRPMRPNS QPPKPSQVTQ TRASVTFPRP QGQLILPVEL
TSEVILRSAP ITHSLNSSEN ATTIKESIV
