SCNAA_ONYTO
ID SCNAA_ONYTO Reviewed; 1959 AA.
AC P0DMA5; U6BRW2;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 1.
DT 25-MAY-2022, entry version 29.
DE RecName: Full=Sodium channel protein type 10 subunit alpha;
GN Name=Scn10a; Synonyms=Sns;
OS Onychomys torridus (Southern grasshopper mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Neotominae; Onychomys.
OX NCBI_TaxID=38674;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF 746-ILE-ALA-747;
RP GLN-859 AND GLU-862.
RX PubMed=24159039; DOI=10.1126/science.1236451;
RA Rowe A.H., Xiao Y., Rowe M.P., Cummins T.R., Zakon H.H.;
RT "Voltage-gated sodium channel in grasshopper mice defends against bark
RT scorpion toxin.";
RL Science 342:441-446(2013).
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 {ECO:0000269|PubMed:24159039}.
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. Interacts with
CC NEDD4 and NEDD4L (By similarity). {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 -!- 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:0000305}.
CC -!- PTM: Phosphorylation at Ser-1453 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 816) 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 -!- MISCELLANEOUS: O.torridus is resistant to the pain-inducing components
CC of the venom of its prey, the bark scorpion (Centruroides
CC sculpturatus). It is most probably due to the unique inhibition by some
CC venom components of the Scn10a sodium-channel in those rodents.
CC Inhibition of Snc10a would, in turn, inhibit sodium currents, block
CC action potential propagation and induce analgesia. Glu-862 plays a
CC central role in that inhibition and its replacement by a Gln, the
CC corresponding amino acid found in the M.musculus ortholog, prevents the
CC inhibition of Snc10a. This would explain why the venom induces pain in
CC M.musculus but not in O.torridus (PubMed:24159039).
CC {ECO:0000305|PubMed:24159039}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.8/SCN10A subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A pain soothed - Issue 157
CC of January 2014;
CC URL="https://web.expasy.org/spotlight/back_issues/157/";
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DR EMBL; KF717604; AHA38158.1; -; mRNA.
DR AlphaFoldDB; P0DMA5; -.
DR SMR; P0DMA5; -.
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 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Repeat; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW Voltage-gated channel.
FT CHAIN 1..1959
FT /note="Sodium channel protein type 10 subunit alpha"
FT /id="PRO_0000424959"
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..340
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 341..365
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 366..372
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 373..398
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..659
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 660..684
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 685..695
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 696..719
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 720..727
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 728..747
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 748..753
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 754..773
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 774..789
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 790..810
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 811..834
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 835..855
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 856..864
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 865..890
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 891..1149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1150..1173
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1174..1186
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1187..1212
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1213..1218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1219..1240
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1241..1244
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1245..1266
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1267..1285
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1286..1313
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1314..1355
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1356..1377
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1378..1393
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1394..1420
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1421..1473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1474..1497
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1498..1508
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1509..1532
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1533..1538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1539..1562
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1563..1574
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1575..1596
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1597..1611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1612..1634
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1635..1648
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1649..1671
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1672..1699
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1700..1724
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1725..1959
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 116..404
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 647..911
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1142..1451
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1460..1759
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1853..1882
FT /note="IQ"
FT REGION 30..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1004..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1071..1097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1901..1959
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..469
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1907..1944
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 1453
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 276..318
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 857..866
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT MUTAGEN 746..747
FT /note="IA->TS: No effect on inhibition by the venom of
FT Centruroides sculpturatus."
FT /evidence="ECO:0000269|PubMed:24159039"
FT MUTAGEN 859
FT /note="Q->E: Complete loss of inhibition by the venom of
FT Centruroides sculpturatus; when associated with Q-862."
FT /evidence="ECO:0000269|PubMed:24159039"
FT MUTAGEN 862
FT /note="E->Q: Almost complete loss of inhibition by the
FT venom of Centruroides sculpturatus. Complete loss of
FT inhibition by the venom of Centruroides sculpturatus; when
FT associated with E-859."
FT /evidence="ECO:0000269|PubMed:24159039"
SQ SEQUENCE 1959 AA; 220523 MW; FE84EC9345B5EB74 CRC64;
MEFPIGSVGT TNFRRFTPES LAEIEKQIAA HGAAKKARAK HGERKGQDEK PRPQLDLKAC
NQLPRFYGEL PAELVGEPLE DLDPFYSTHR TFMVLNKGRT ISRFSATWAL WLFSPFNLIR
RTAIKVSVHA WFSIFITITI LFNCVCMTQN DLPEKIEYAF TVIYTFEALI KILARGFCLN
EFTYLRDPWN WLDFSVITLA YVGAAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI
HSVRKLADVT ILTVFCLSVF ALVGLQLFKG NLKNKCIKRS TDPHNAYNFS SQMADNFYIK
NGTTEPLLCG NGSDAGHCPS GYICLKTSDN PDFNYTSFDS FAWAFLSLFR LMTQDSWERL
YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE EQNQATIAEI EAKEKKFQEA
LEVLQKEQEV LAALGIDTTS LHSHNGSPLA PKNANERKHR IKSRVSEGST DDNRSPQSDP
YNQRRMSFLG LSSGRRRASH SSVFHFRAPS QDVSFPDGIT DDGVFHGDHE SHRSSLLLAR
GAGQAGPLPR SPLASSPNPG PGHREEGQLT APTGELTTGA PEDLALEAAG QKKNFLSAEY
LNEPFRAQRA MSVVSIMTSV IEELEESKLR CPPCLINLAQ KYLIWECCPK WMKFKMVLFE
LVTDPFAELT ITLCIVVNTI FMAMEHYPMT DAFDAMLQAG NIVFTVFFTM EMAFKIIAFD
PYYYFQKKWN VFDCVIVTVS LLELSIAKKG SLSVLRTFRL LRVFKLAKSW PTLNTLIKII
GNSVGALGNL TFILAIIVFI FALVGKQLLG EDYGCRKDGT ALWNEGQLRW HMCDFFHSFL
VIFRILCGEW IENMWVCMQV SEKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA
PEDDGEVNNL QVALARTQAF GQRASQAISS YFSSHCRLRW PKVGSQLGVK PSLTSSKAEH
HITADAVNTA VGTSAKPALS GPKEDPRDFI TDANVWVSVP IAEGESDLDE LEEDIEQNSQ
SSWREESPKG QQDQLWQIQR CEDHQVPNSP GSGMSSEDLA SYLGERWKSE ATPQVPAEGV
DDTSSSEGST VDCPDPEEIL KKIPELADDL EEPDDCFTEG CTRHCPCCKV STSKFPWTTG
WQVRKTCYRI VEHSWFESFI IFMILLSSGA LAFEDNYLEQ KPRVKSMLEY TDRVFTFIFV
FEMLLKWVAY GFKKYFTNAW CWLDFLIVNI SLTSLIAKIL DYSDVASLKA LRTLRALRPL
RALSRFEGMR VVVDALVGAI PSIMNVLLVC LIFWLIFSIM GVNLFAGKFS RCIDTSNNPF
SVVNSTIVNN KSECRNQNHT GHFFWVNVKV NFDNVAMGYL ALLQVATFKG WMDIMYAAVD
SREINSQPQW EDNLYMYLYF VVFIIFGGFF TLNLFVGVII DNFNQQKKKL GGQDIFMTEE
QKKYYNAMKK LGSKKPQKPI PRPLNKYQGF VFDIVTRQAF DIIIMVLICL NMITMMVETD
GQSEEKTKIL GRINQFFVAV FTGECVMKMF ALRQYYFTNG WNVFDFIVVI LSIGSLVFSA
ILKSLESYFS PTLFRVIRLA RIGRILRLIR AAKGIRTLLF ALMMSLPALF NIGLLLFLVM
FIYSIFGMAS FANVVEEAGI DDMFNFQTFG NSMLCLFQIT TSAGWDGLLS PILNTGPPYC
DPNLSNNNTS KGNCGSPTVG IVFFTTYIII SFLIVVNMYI AVILENFNVA TEESTEPLSE
DDFDMFYETW EKFDPEATQF IAFSALSDFA DTLSGPLRIP KPNQNILIQM DLPLVPGDKI
HCLDILFAFT KNVLGESGEL DSLKTNMEEK FMATNLSKAS YEPIATTLRW KQEDISATVI
QKAYRSYVLQ RSLTLSNPLR VPRAEDDDAP LPGEGYVTFM ANDSGRLPDK SETTSATSFP
PSYDSVTRGL SDRVNISTSN SMHNEDEVTS KEGDSPGPQ
