SCN4A_HORSE
ID SCN4A_HORSE Reviewed; 1834 AA.
AC Q28371;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Sodium channel protein type 4 subunit alpha;
DE AltName: Full=Sodium channel protein skeletal muscle subunit alpha;
DE AltName: Full=Sodium channel protein type IV subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.4;
GN Name=SCN4A;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RA Stephan D.A., Wang J., Spier S., Hoffman E.P.;
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INVOLVEMENT IN HYPP, VARIANT HYPP LEU-1416, AND FUNCTION.
RX PubMed=1338908; DOI=10.1038/ng1092-144;
RA Rudolph J.A., Spier S.J., Byrns G., Rojas C.V., Bernoco D., Hoffman E.P.;
RT "Periodic paralysis in quarter horses: a sodium channel mutation
RT disseminated by selective breeding.";
RL Nat. Genet. 2:144-147(1992).
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 (By similarity). Required for normal muscle fiber
CC excitability, normal muscle contraction and relaxation cycles, and
CC constant muscle strength in the presence of fluctuating K(+) levels
CC (PubMed:1338908). {ECO:0000250|UniProtKB:P35499,
CC ECO:0000269|PubMed:1338908}.
CC -!- ACTIVITY REGULATION: Channel activity is regulated by the ancillary
CC beta subunit SCN1B. SCN1B strongly enhances the presence of the pore-
CC forming alpha subunit at the cell surface (By similarity). Interaction
CC with SCN1B is required for rapid channel inactivation and rapid
CC recovery after inactivation, and prevents decrease of channel activity
CC in response to repetitive, high-frequency depolarizations. The channel
CC is inhibited by tetrodotoxin (By similarity).
CC {ECO:0000250|UniProtKB:P15390, ECO:0000250|UniProtKB:P35499}.
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. Interacts with SCN1B (By similarity). Heterooligomer
CC with SCN2B or SCN4B; disulfide-linked (By similarity). Interacts with
CC the PDZ domain of the syntrophins SNTA1, SNTB1 and SNTB2 (By
CC similarity). Interacts with the conotoxin GVIIJ (By similarity).
CC {ECO:0000250|UniProtKB:P04775, ECO:0000250|UniProtKB:P15390,
CC ECO:0000250|UniProtKB:Q9ER60, ECO:0000250|UniProtKB:Q9JJV9}.
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 -!- PTM: Phosphorylation at Ser-1325 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: Note=Defects in SCN4A are the cause of periodic paralysis
CC hyperkalemic (HYPP). HYPP is an autosomal dominant channelopathy
CC characterized by episodic flaccid generalized muscle weakness
CC associated with high levels of serum potassium. HYPP is frequently
CC found in Quarter Horses, the most popular equine breed in the United
CC States. {ECO:0000269|PubMed:1338908}.
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; U25990; AAA67366.1; -; mRNA.
DR RefSeq; NP_001075230.1; NM_001081761.1.
DR AlphaFoldDB; Q28371; -.
DR SMR; Q28371; -.
DR STRING; 9796.ENSECAP00000005581; -.
DR GeneID; 100049793; -.
DR KEGG; ecb:100049793; -.
DR CTD; 6329; -.
DR InParanoid; Q28371; -.
DR OrthoDB; 56920at2759; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; ISS:UniProtKB.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0100001; P:regulation of skeletal muscle contraction by action potential; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
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; IPR008052; Na_channel_a4su_mammal.
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 PRINTS; PR01665; NACHANNEL4.
DR PROSITE; PS50096; IQ; 1.
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; Voltage-gated channel.
FT CHAIN 1..1834
FT /note="Sodium channel protein type 4 subunit alpha"
FT /id="PRO_0000371315"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 132..150
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 151..157
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 158..178
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 179..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 193..210
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 211..216
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 217..233
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 234..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 253..272
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 273..385
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 386..410
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 411..417
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 418..438
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 439..572
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 573..591
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 592..602
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 603..622
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 623..636
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 637..656
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 657..658
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 659..676
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 677..692
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 693..711
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 712..740
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 741..761
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 762..772
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 773..791
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 792..1029
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1030..1047
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1048..1060
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1061..1079
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1080..1093
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1094..1112
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1113..1120
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1121..1139
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1140..1156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1157..1176
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1177..1227
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1228..1249
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1250..1266
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1267..1288
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1289..1351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1352..1369
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1370..1380
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1381..1399
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1400..1411
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1412..1429
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1430..1442
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1443..1459
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1460..1478
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1479..1496
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1497..1518
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1519..1541
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1542..1571
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1572..1594
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT TOPO_DOM 1595..1834
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 113..448
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 554..826
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1010..1323
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1332..1630
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1724..1753
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 486..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 853..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1307..1309
FT /note="Important for rapid channel inactivation"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT REGION 1776..1834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..523
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 867..886
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 972..987
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1776..1791
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1812..1826
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 401
FT /note="Important for inhibition by tetrodotoxin"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT MOD_RES 1325
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250"
FT CARBOHYD 214
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 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 280..354
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 363..369
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 723
FT /note="Interchain; with SCN2B or SCN4B"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT DISULFID 723
FT /note="Interchain; with the conotoxin GVIIJ (when the
FT channel is not linked to SCN2B or SCN4B; the bond to SCN2B
FT or SCN4B protects the channel from the inhibition by
FT toxin)"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT DISULFID 725..731
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT DISULFID 1550..1565
FT /evidence="ECO:0000250|UniProtKB:P35499"
FT VARIANT 1416
FT /note="F -> L (in HYPP; found in a Quarter Horse lineage
FT segregating the disease)"
FT /evidence="ECO:0000269|PubMed:1338908"
SQ SEQUENCE 1834 AA; 207487 MW; 01D62B25CD577D97 CRC64;
MASSSLPNLV PLGPESLRPF TRASLAAIER RALEEEARLQ RNKQMEIQET ERNARSDLEA
GKNLPLIYGD PPPEVIGIPL EDLDPYYSNK KTFIVLNKGK AIFRFSATPA LYMLSPFSII
RRSAIKVLIH SLFSMFIMIT ILPNCVVMTM SDPPPWPIHV ENTFTGINTF ESLIKMLARG
FCIDDFTFLR DPWNWLDFSV IMMAYLTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV
GALIQSVKKL SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPQPFNDT NTTWYGNDTW
YSNDTWNSND TWSSNDMWNS HESMASNYTF DWDAYINDEG NFYFLEGAKD ALLCGNSSDA
GHCPEGYKCI KTGRNPNYGY TSHDTFSWAF LALFRLMIQD YWENLFQLTL RAAGKTYMIF
FVVIIFLGSF YLINLILAVV TMAYAEQNEA TLAEDQEKEE EFQQMMEKFQ KQQEELEKAK
ADQALEGGEA GGDPAHSKDC NGSLDTSPGE KGPPRQSCSA DSGVSDAMEE LEEAHQKCPP
WWYKCAHKVL IWNCCTPWVK FKNIIHLIVM DPFVDLGITI CIVLNTLFMA MEHYPMTEHF
DKVLTVGNLV FTGIFTAEMV LKLIALDPYE YFQQGWNVFD SIIVTLSWVE LGLVNVKGLS
VLRSFRLVRS LKLAKSWPTL NMFIRIIGNS GGGLGNLTLV LAIIVVNFSV VGMQLFGKNY
KECVCKNASD CALPRWKMCD FFHSFLIVLR ILCGEWIEPM WGFMEVAGQA MFLTVLLMVM
VNGNLVDLDL FLALLLNPLN SDNLSASDED GEMNNLQISS WPIKLGICFA NAFLLGLLHG
KILSPKDIML SLGDPGEAGE AGEAEESAPE DEKKEPPPED DDKDLKKDNH ILNHMGLVDG
TPTSIELDHL NFINNPYLTI HVPIASEESD LEMPTEEETD TFSEPEDGKK PLQPLDGNSS
VCSTADYKPP EEDPEEQAEE NPEGEQPEEC FTEACVQRFP CLSVDISQGR GKMWWTLRRA
CFKIVEHHWF KTFNSSLILL NSGTLAFEDI YIEQRRVIRT ILEYADKVFT YIFIMEMLLK
WVAYGFKVYF TNAWCWLDFL IVDVSIISLV ANWLGYSELG PIKSLRTLRA LRPLRALSRF
EGMRVVVNAL LGAIPSIMNV LLVCLIFWVI FSIMGVNLFA AKIYYFINTT TSERFDISGV
NNKSECESLI HTGQVRWLNV KVNYDNVGLG YLSLLQVATF KGWMDIMYSA VDSREQEEQP
QYEVNIYMYL YFVIFIIFGS FFTINSLIRL IIVNFNQQKK KLGGKDIFMT EEQKKYYNAM
KKLGSKKPQK PIPRPQNKIQ GMVYDFVTKQ VFDITIMILI CLNMVTMMVE TDDQSQLKVD
ILYNINMVFI IVFTGECVLK MFALRQNYFT VGWNIFDFVV VILSIVGLAL SDLIQKYFVS
PTLFRVIRLA RIGRVLRLIR GAKGIRTLLF ALMMSLPALF NIGLLLILVM FIYSIFGMSN
FAYVKKESGI DDMFNFETFG NSIICLFEIT TSAGWDGLLN PILNSGPPDC DPTLENPGTS
VRGDCGNPSI GICFFCSYII ISFLIVVNMY IAIILENFNV ATEESSDPLG EDDFEIFFEK
WEKFGPDATQ FIDYSRLSDF VDTLQEPLRI AKPNKIKLIT LDLPMVPGDK IHCLDILFAL
TKEVLGDSGE MDALKETMEE KFMAANPSKV SYEPITTTLK RKQEEVCAIK IQRAYRRHLL
QRSVKQASYM YRHSQDGSGD GAPEKEGLIA NTMSKMYGRE NGNSGVQNKG EERGSTGDAG
PTMGLTPINP SDSALPPSPP PGLPLHPGVK ESLV
