SCNAA_CANLF
ID SCNAA_CANLF Reviewed; 1962 AA.
AC O46669;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 120.
DE RecName: Full=Sodium channel protein type 10 subunit alpha;
DE AltName: Full=NaNG;
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Mongrel; TISSUE=Nodose ganglion;
RX PubMed=9427539; DOI=10.1016/s0378-1119(97)00433-2;
RA Chen J., Ikeda S.R., Lang W., Isales C.M., Wei X.;
RT "Molecular cloning of a putative tetrodotoxin-resistant sodium channel from
RT dog nodose ganglion neurons.";
RL Gene 202:7-14(1997).
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 (By similarity). {ECO:0000250}.
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 nodose ganglia, but not in cortex,
CC hippocampus, cerebellum, liver, heart and skeletal muscle.
CC {ECO:0000269|PubMed:9427539}.
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-1458 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 825) 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 -!- 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; U60590; AAC39164.1; -; mRNA.
DR RefSeq; NP_001003203.1; NM_001003203.1.
DR AlphaFoldDB; O46669; -.
DR BMRB; O46669; -.
DR SMR; O46669; -.
DR STRING; 9615.ENSCAFP00000011447; -.
DR PaxDb; O46669; -.
DR PRIDE; O46669; -.
DR GeneID; 477026; -.
DR KEGG; cfa:477026; -.
DR CTD; 6336; -.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; O46669; -.
DR OrthoDB; 172471at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; 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 GO; GO:0019233; P:sensory perception of pain; IEA:InterPro.
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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..1962
FT /note="Sodium channel protein type 10 subunit alpha"
FT /id="PRO_0000048506"
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..350
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 351..375
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 376..382
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 383..408
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..668
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 669..693
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 694..704
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 705..728
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 729..736
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 737..756
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..762
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 763..782
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 783..798
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 799..819
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 820..843
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 844..864
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 865..873
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 874..899
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 900..1154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1155..1178
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1179..1191
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1192..1217
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1218..1223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1224..1245
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1246..1249
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1250..1271
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1272..1290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1291..1318
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1319..1360
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1361..1382
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1383..1398
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1399..1425
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1426..1478
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1479..1502
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1503..1513
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1514..1537
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1538..1543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1544..1567
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1568..1579
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1580..1601
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1602..1616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1617..1639
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1640..1653
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1654..1676
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1677..1704
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1705..1729
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1730..1962
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 116..414
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 656..920
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1147..1456
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1465..1764
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1858..1887
FT /note="IQ"
FT REGION 32..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 452..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 521..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1035
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1914..1962
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..55
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..479
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1914..1954
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 1458
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 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 828
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1693
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 276..328
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 866..875
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
SQ SEQUENCE 1962 AA; 220702 MW; 5D32D20D4AF47A68 CRC64;
MEFPFGSLET TNFRRFTPES LVEIEKRIAA KQAAKKAKGK HREQKDQEEK PRPQLDLKAC
NQPPKFYGEL PAELVGEPLE DLDPFYSTHR TFMVLDKGRT ISRFSATRAL WLFSPFNLIR
RTAIKVSVHS WFSLFITVTI LVNCVGMTQT ELPDRIEYVF TVIYTFEALI KILARGFCLN
EFAYLRDPWD WLDFSVITLA YIGEATALRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI
HSVRKLADVT ILTVFCLSVF ALVGLQLFKG NLKNKCVKNC AALNETGNYS SYGKQEWNFC
HRDEDFYYNK PGTSDPLLCG NGSDAGHCPK GYLCLKTSDN PDFNYTSFDS FAWAFLSLFR
LMTQDSWERL YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE EQNQATIDEI
EAKEKTFQET LEMPRKEQEV LAALGIDTAS LHSCNGSPLP SKNASERMRR MKPRVSEGST
DDNKSPQSDP YNQRRMSFLG LTSGRRRASH GSVFHFRTPC LDTSFPDGVT DDGVFPGDRE
SHRGSLLLGG GTSQQGPLLR SPLPQPPNPG SGHGEDGHST LPTGELAPGG IEVSAFDAGQ
KKTFLSAEYL NEPFRAQRAM SVVSIMTSVL EELEESERRC PPCLTSFAQK YLIWECCPTW
VKLKTVLFGI VTDPFAELTT TLCIVVNTVF MAMEHHGMSS AFEAMLQIGN IVFTVFFTAE
MVFKIIAFDP YYYFQKRWNI FDCIIVTVSL IELGAARKGS LSVLRTFRLL RVFKLAKSWP
TLNTLIKIIG NSVGALGNLT IILAIIVFVF ALVGKQLLGE NYRDNRRNIS APNEEWPRWH
MHDFFHSFLI VFRILCGEWI ENMWACMEVG QKSICLILFL TVMVLGNLVV LNLFTALLLN
SFSADNLATP DEDGEVNNLQ VALARIQAFG HRTKKAICNF FTRPCLLPWP KAEPQLVVKL
PLSSSKAENH IAANAAVGSP GGLSVSRGLR DDHSDFITNP NIWVSVPIAE GESDLDDLEE
DGEEDSQSSQ QEVILQGQEQ LQVETCEGHT APRSPGSGMS SEDLASYVDE KWKDEAVAQA
PAEGGDDSSS SGGSTVDCLD PEEILRKIPE LADDLEEPDD CFTEGCLRRC PCCKVDISKF
PWTVGWQVRK TCYRIVEHSW FESFIIFMIL LSSGSLAFED YHLDQKPTVK ALLEYTDRMF
TFIFVLEMLL KWVAYGFKKY FTNAWCWLDF LIVNISLISL IAKILQYSDV ASIKALRTLR
ALRPLRALSR FEGMRVVVDA LVGAIPSIMN VLLVCLIFWL IFSTMGVNFF AGKFGRCINK
TNEYFSLVPL SIVNNISDCK YQNHTGSFFW VNVKVNFDNV AMGYLALLQV ATFKGWMDIM
YAAVDARDVN LQPKWEDNVY MYLYFVIFII FGGFFTLNLF VGVIIDNFNQ QKKKLGGQDI
FMTEEQKKYY NAMKKLGSKK PQKPIPRPLN KYQGFVFDIV TKQAFDIVIM VLICLNMITM
MVETDEQSAE KTKILNKINQ FFVAVFTGEC VMKMFALRHY YFTNGWNVFD FIVVVLSIGS
LVFSVILTSL ENYFSPTLFR VIRLARIGRI LRLIRAAKGI RTLLFALMMS LPALFNIGLL
LFLVMFIYSI FGMASFPHVS WEAGIDDMFN FQTFANSMLC LFQITTSAGW DGLLSPILNT
GPPYCDPNLP NSNGSRGNCG SPAVGILFFT TYIIISFLIV VNMYIAVILE NFNVATQESS
EPLSEDDFDM FYETWEKFDP EATQFITFSA LSDFADTLSG PLRIPKPNQN ILIQMDLPLV
PGDKIHCLDI LFAFTKNVLG ESGELDSLKA NIEEKFMATN VSKASYEPIA TTLRWKQEDI
SATVIQKAYR SYVLHRSMTI SNPPAVPRAE EAVPPPDEAF VEFMVNENCA LPDKSETASA
ASFPPSYDSV TRGLSDQINM STSSSMQNED EGTSKKVTAP GP
