SCN9A_RABIT
ID SCN9A_RABIT Reviewed; 1984 AA.
AC Q28644;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 120.
DE RecName: Full=Sodium channel protein type 9 subunit alpha {ECO:0000250|UniProtKB:Q15858};
DE AltName: Full=Nas {ECO:0000303|PubMed:7479931};
DE AltName: Full=Schwann cell sodium channel;
DE AltName: Full=Sodium channel protein type IX subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.7;
GN Name=SCN9A {ECO:0000250|UniProtKB:Q15858};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Schwann cell;
RX PubMed=7479931; DOI=10.1073/pnas.92.24.11034;
RA Belcher S.M., Zerillo C.A., Levenson R., Ritchie J.M., Howe J.R.;
RT "Cloning of a sodium channel alpha subunit from rabbit Schwann cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11034-11038(1995).
CC -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability of
CC excitable membranes. Assuming opened or closed conformations in
CC response to the voltage difference across the membrane, the protein
CC forms a sodium-selective channel through which Na(+) ions may pass in
CC accordance with their electrochemical gradient. It is a tetrodotoxin-
CC sensitive Na(+) channel isoform. Plays a role in pain mechanisms,
CC especially in the development of inflammatory pain.
CC {ECO:0000250|UniProtKB:Q15858}.
CC -!- SUBUNIT: The sodium channel complex consists of a large, channel-
CC forming alpha subunit (SCN9A) regulated by one or more beta subunits
CC (SCN1B, SCN2B, SCN3B and SCN4B) (By similarity). SCN1B and SCN3B are
CC non-covalently associated with SCN2A. SCN2B and SCN4B are disulfide-
CC linked to SCN2A (By similarity). Interacts with NEDD4 and NEDD4L (By
CC similarity). Interacts with the conotoxin GVIIJ (By similarity).
CC {ECO:0000250|UniProtKB:O08562, ECO:0000250|UniProtKB:Q15858,
CC ECO:0000250|UniProtKB:Q62205}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q15858};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:O08562}. Note=In
CC neurite terminals. {ECO:0000250|UniProtKB:O08562}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q28644-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q28644-2; Sequence=VSP_012030;
CC -!- TISSUE SPECIFICITY: Expressed in the sciatic nerve, spinal cord,
CC brainstem, cerebellum and cortex, but not expressed in the lung,
CC skeletal and cardiac muscles, kidney and liver.
CC {ECO:0000269|PubMed:7479931}.
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: Phosphorylation at Ser-1487 by PKC in a highly conserved
CC cytoplasmic loop increases peak sodium currents.
CC {ECO:0000250|UniProtKB:Q15858}.
CC -!- PTM: Ubiquitinated by NEDD4L; which may promote its endocytosis. Does
CC not seem to be ubiquitinated by NEDD4. {ECO:0000250|UniProtKB:Q62205}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.7/SCN9A subfamily. {ECO:0000305}.
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DR EMBL; U35238; AAA89159.1; -; mRNA.
DR RefSeq; NP_001075827.1; NM_001082358.1. [Q28644-1]
DR AlphaFoldDB; Q28644; -.
DR SMR; Q28644; -.
DR STRING; 9986.ENSOCUP00000020201; -.
DR PRIDE; Q28644; -.
DR GeneID; 100009210; -.
DR KEGG; ocu:100009210; -.
DR CTD; 6335; -.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; Q28644; -.
DR OrthoDB; 56920at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0048266; P:behavioral response to pain; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; 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; IPR001696; Na_channel_asu.
DR InterPro; IPR044564; Na_chnl_inactivation_gate.
DR InterPro; IPR010526; Na_trans_assoc.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR028803; SCN9A.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 1.
DR PANTHER; PTHR10037:SF221; PTHR10037:SF221; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR Pfam; PF06512; Na_trans_assoc; 1.
DR Pfam; PF11933; Na_trans_cytopl; 1.
DR PRINTS; PR00170; NACHANNEL.
DR SMART; SM00015; IQ; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Cell projection; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW Voltage-gated channel.
FT CHAIN 1..1984
FT /note="Sodium channel protein type 9 subunit alpha"
FT /id="PRO_0000048504"
FT TOPO_DOM 1..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 127..145
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 146..152
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 153..173
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 174..187
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 188..205
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 206..211
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 212..228
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 229..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 248..267
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 268..344
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 345..369
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 370..376
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 377..397
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 398..741
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 742..760
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 761..771
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 772..791
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 792..805
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 806..825
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 826..827
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 828..845
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 846..861
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 862..880
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 881..909
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 910..930
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 931..943
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 944..964
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 965..1190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1191..1208
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1209..1221
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1222..1240
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1241..1254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1255..1273
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1274..1281
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1282..1300
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1301..1317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1318..1337
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1338..1389
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1390..1411
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1412..1428
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1429..1450
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1451..1513
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1514..1531
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1532..1542
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1543..1561
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1562..1573
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1574..1591
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1592..1604
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1605..1621
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1622..1640
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1641..1658
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1659..1680
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1681..1703
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1704..1733
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1734..1756
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1757..1984
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 112..408
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 723..986
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1177..1485
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1494..1792
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1886..1915
FT /note="IQ"
FT REGION 26..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..517
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1087..1146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1924..1984
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..51
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..517
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..579
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 591..610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1930..1955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1957..1984
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 819
FT /note="Is directly targeted by the spider protoxin-II"
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT SITE 824
FT /note="Is directly targeted by the spider protoxin-II"
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT MOD_RES 1487
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT CARBOHYD 209
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 1349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 275..322
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 892
FT /note="Interchain; with SCN2B or SCN4B"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT DISULFID 892
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 894..900
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT DISULFID 932..941
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 1347..1367
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT DISULFID 1712..1727
FT /evidence="ECO:0000250|UniProtKB:Q15858"
FT VAR_SEQ 200..229
FT /note="YLTEFVNLGNVSALRTFRVLRALKTISVIP -> YVTEFVDLGNVSALRTFR
FT VLRALKTISVIP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7479931"
FT /id="VSP_012030"
SQ SEQUENCE 1984 AA; 225751 MW; 98F76860C9866AA0 CRC64;
MAMLPPPGPQ SFVRFTKQSL ALIEQRIAEG KTKEPKEEKK DDHDEGPKPS SDLEAGKQLP
FIYGDIPAGM VSEPLEDLDP YYADKKTFIV LNKGKAIFRF NATPALYILS PFSPLRRISI
KILVHSLFSM LIMCTILTNC IFMTMNNPAE WTKNVEYTFT GIYTFESLVK IFARGFCVGE
FTFLRDPWNW LDFIVIVFAY LTEFVNLGNV SALRTFRVLR ALKTISVIPG LKTIVGALIQ
SVKKLSDVII LTVFCLSVFA LIGLQLFMGH LKHKCLRKIE NETLESIMSS IESEEDYKKY
FYYLEGSKDA LLCGFSTDSG QCPEGYYCVK AGRNPDYGYT SFDTFSWAFL ALFRLMTQDY
WENLYQQTLR AAGKTYMIFF VVVIFLGSFY LINLILAVVA MAYEEQNQAN IEEAKQKELE
FQQMLDRLKK EQEEAEAIAA AAAEYTSIGR SRIMGLSESS SETSKLSSKS AKERRNRRKK
KNQKKLSSGE EKGDDEKLSK SESEESISRK QFHLGVEGHR LAREKRLSAP NQSPLSIRGS
LFSARRSSRT SLFSFKGRGK DIGSETEFAD DEHSIFGDNE SRRGSLFVPQ RPQERRSSNL
SQASRSPPML QMNGKMHSAV DCNGVVSLVD GPSALMLPNG QLLPEVIIDK ATSDDSGTTQ
IRKKRRSSSY LLSEDMLNDP HLRQRAMSRA SILTNTVEEL EESRQKCPSW WYRFAHTFLI
WNCSPFWIKF KKFIYIIVMD PFVDLAITIC IVLNTLFMAM EHHPMTEEFK NVLVVGNLVF
TGIFAAEMVL KLIAMDPYEY FQVGWNVFDS LIVTLSLVEL FLADVEGLSV LRSFRLLRVF
KLAKSWPTLN MLIKIIGNSV GPLGNLTLVL AIIVFIFAVV GMQLFGKSYK ECVCKINDDC
SLPRWHMNDF FHSFLIVFRV LCGEWIETMW DCMEVAGQAM CLIVYMMVMV IGNLVVLNLF
LALLLSSFSS DNLSAIEEDT DANNLQIAVT RIKKGINYVK QTLRELILKA FSKKPKISKE
IRQAEDLNSK KENYISNRTL AEMSKDYNFH KEKDKISGFG SSMDKYLMEE SDHQSFIHNP
SLTVTVPIAP GESDLENMNT EELSSDSESE YSKERLNRSS SSECSTVDNA LPGEGEEAEA
EPVNSDEPEA CFTDGCVRRF PCCQVSIESG KGKIWWNIRK TCYRIVEHSW FESFIVLMIL
LSSGALAFED IYIEKKKTIK IILEYADKIF TYIFILEMLL KWVAYGYKTY FTNAWCWLDF
LIVDVSLVTL VANTLGYSDL GPIKSLRTLR ALRPLRALSR FEGMRVVVNA LIGAIPSIMN
VLLVCLIFWL IFSIMGVNLF AGKFYQCVNT TDDSRFPTKQ VSNRSECFAL MNGSQNVRWK
NLKVNFDNVG LRYLSLLQVA TFKGWMDIMY AAVDSVNVDQ QPSYEHNLYM YIYFVIFIIF
GSFFTLNLFI GVIIDNFNQQ KKKLGGQDIF MTEEQKKYYN AMKKLGSKKP QKPIPRPGNK
FQGCIFDLVT NQAFDITIMI LICLNMVTMM VEKEGQSDYM TDVLYWINVV FIILFTGECV
LKLISLRHYY FTIGWNIFDF VVVILSIVGM FLAELIETYF VSPTLFRVIR LARIGRILRL
IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIYAIFGM SNFAYVKKEA GINDMFNFET
FGNSMICLFQ ITTSAGWDGL LAPILNSAPP DCDPKKVHPG SSTEGDCGSP SVGIFYFVSY
IIISFLVVVN MYIAVILENF SVATEESTEP LSEDDFEMFY EVWEKFDPDA TQFIEYSKLS
DFAAALDPPL LIAKPNKVQL IAMDLPMVSG DRIHCLDILF AFTKRVLGES GEMDSLRSQM
EERFMSANPS KVSYEPITTT LKRKQEDVSA TVIQRAYRRY RLRQNVKNIS SIYIKEGDKD
DDLPNKGDIV FDNVNSSSPE KTDATASTIS PPSYDSVTKP DKEKYEKDKT EKEDKGKDGK
ETKK
