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Protein

Sodium channel protein type 10 subunit alpha

Gene

Scn10a

Organism
Onychomys torridus (Southern grasshopper mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.1 Publication

Miscellaneous

O.torridus is resistant to the pain-inducing components of the venom of its prey, the bark scorpion (Centruroides sculpturatus). It is most probably due to the unique inhibition by some venom components of the Scn10a sodium-channel in those rodents. Inhibition of Snc10a would, in turn, inhibit sodium currents, block action potential propagation and induce analgesia. Glu-862 plays a central role in that inhibition and its replacement by a Gln, the corresponding amino acid found in the M.musculus ortholog, prevents the inhibition of Snc10a. This would explain why the venom induces pain in M.musculus but not in O.torridus (PubMed:24159039).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 10 subunit alpha
Gene namesi
Name:Scn10a
Synonyms:Sns
OrganismiOnychomys torridus (Southern grasshopper mouse)
Taxonomic identifieri38674 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaCricetidaeNeotominaeOnychomys

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity

  • Note: It can be translocated to the cell membrane through association with S100A10.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 125CytoplasmicCuratedAdd BLAST125
Transmembranei126 – 149Helical; Name=S1 of repeat ISequence analysisAdd BLAST24
Topological domaini150 – 154ExtracellularCurated5
Transmembranei155 – 174Helical; Name=S2 of repeat ISequence analysisAdd BLAST20
Topological domaini175 – 187CytoplasmicCuratedAdd BLAST13
Transmembranei188 – 206Helical; Name=S3 of repeat ISequence analysisAdd BLAST19
Topological domaini207 – 212ExtracellularCurated6
Transmembranei213 – 232Helical; Voltage-sensor; Name=S4 of repeat ISequence analysisAdd BLAST20
Topological domaini233 – 248CytoplasmicCuratedAdd BLAST16
Transmembranei249 – 272Helical; Name=S5 of repeat ISequence analysisAdd BLAST24
Topological domaini273 – 340ExtracellularCuratedAdd BLAST68
Intramembranei341 – 365Pore-formingBy similarityAdd BLAST25
Topological domaini366 – 372ExtracellularCurated7
Transmembranei373 – 398Helical; Name=S6 of repeat ISequence analysisAdd BLAST26
Topological domaini399 – 659CytoplasmicCuratedAdd BLAST261
Transmembranei660 – 684Helical; Name=S1 of repeat IISequence analysisAdd BLAST25
Topological domaini685 – 695ExtracellularCuratedAdd BLAST11
Transmembranei696 – 719Helical; Name=S2 of repeat IISequence analysisAdd BLAST24
Topological domaini720 – 727CytoplasmicCurated8
Transmembranei728 – 747Helical; Name=S3 of repeat IISequence analysisAdd BLAST20
Topological domaini748 – 753ExtracellularCurated6
Transmembranei754 – 773Helical; Voltage-sensor; Name=S4 of repeat IISequence analysisAdd BLAST20
Topological domaini774 – 789CytoplasmicCuratedAdd BLAST16
Transmembranei790 – 810Helical; Name=S5 of repeat IISequence analysisAdd BLAST21
Topological domaini811 – 834ExtracellularCuratedAdd BLAST24
Intramembranei835 – 855Pore-formingBy similarityAdd BLAST21
Topological domaini856 – 864ExtracellularCurated9
Transmembranei865 – 890Helical; Name=S6 of repeat IISequence analysisAdd BLAST26
Topological domaini891 – 1149CytoplasmicCuratedAdd BLAST259
Transmembranei1150 – 1173Helical; Name=S1 of repeat IIISequence analysisAdd BLAST24
Topological domaini1174 – 1186ExtracellularCuratedAdd BLAST13
Transmembranei1187 – 1212Helical; Name=S2 of repeat IIISequence analysisAdd BLAST26
Topological domaini1213 – 1218CytoplasmicCurated6
Transmembranei1219 – 1240Helical; Name=S3 of repeat IIISequence analysisAdd BLAST22
Topological domaini1241 – 1244ExtracellularCurated4
Transmembranei1245 – 1266Helical; Voltage-sensor; Name=S4 of repeat IIISequence analysisAdd BLAST22
Topological domaini1267 – 1285CytoplasmicCuratedAdd BLAST19
Transmembranei1286 – 1313Helical; Name=S5 of repeat IIISequence analysisAdd BLAST28
Topological domaini1314 – 1355ExtracellularCuratedAdd BLAST42
Intramembranei1356 – 1377Pore-formingBy similarityAdd BLAST22
Topological domaini1378 – 1393ExtracellularCuratedAdd BLAST16
Transmembranei1394 – 1420Helical; Name=S6 of repeat IIISequence analysisAdd BLAST27
Topological domaini1421 – 1473CytoplasmicCuratedAdd BLAST53
Transmembranei1474 – 1497Helical; Name=S1 of repeat IVSequence analysisAdd BLAST24
Topological domaini1498 – 1508ExtracellularCuratedAdd BLAST11
Transmembranei1509 – 1532Helical; Name=S2 of repeat IVSequence analysisAdd BLAST24
Topological domaini1533 – 1538CytoplasmicCurated6
Transmembranei1539 – 1562Helical; Name=S3 of repeat IVSequence analysisAdd BLAST24
Topological domaini1563 – 1574ExtracellularCuratedAdd BLAST12
Transmembranei1575 – 1596Helical; Voltage-sensor; Name=S4 of repeat IVSequence analysisAdd BLAST22
Topological domaini1597 – 1611CytoplasmicCuratedAdd BLAST15
Transmembranei1612 – 1634Helical; Name=S5 of repeat IVSequence analysisAdd BLAST23
Topological domaini1635 – 1648ExtracellularCuratedAdd BLAST14
Intramembranei1649 – 1671Pore-formingBy similarityAdd BLAST23
Topological domaini1672 – 1699ExtracellularCuratedAdd BLAST28
Transmembranei1700 – 1724Helical; Name=S6 of repeat IVSequence analysisAdd BLAST25
Topological domaini1725 – 1959CytoplasmicCuratedAdd BLAST235

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi746 – 747IA → TS: No effect on inhibition by the venom of Centruroides sculpturatus. 1 Publication2
Mutagenesisi859Q → E: Complete loss of inhibition by the venom of Centruroides sculpturatus; when associated with Q-862. 1 Publication1
Mutagenesisi862E → Q: Almost complete loss of inhibition by the venom of Centruroides sculpturatus. Complete loss of inhibition by the venom of Centruroides sculpturatus; when associated with E-859. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004249591 – 1959Sodium channel protein type 10 subunit alphaAdd BLAST1959

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi276 ↔ 318By similarity
Glycosylationi288N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi311N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi334N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei440PhosphoserineBy similarity1
Modified residuei443PhosphoserineBy similarity1
Modified residuei466PhosphoserineBy similarity1
Modified residuei478PhosphoserineBy similarity1
Modified residuei612PhosphoserineBy similarity1
Modified residuei615PhosphoserineBy similarity1
Disulfide bondi857 ↔ 866By similarity
Modified residuei1453Phosphoserine; by PKCBy similarity1

Post-translational modificationi

Ubiquitinated by NEDD4L; which promotes its endocytosis.Curated
Phosphorylation at Ser-1453 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.By similarity
Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 816) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

The channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B and SCN3B; electrophysiological properties may vary depending on the type of the associated beta subunits. Found in a number of complexes with PRX, DYNLT1 and PDZD2. Interacts with proteins such as FSTL1, PRX, DYNLT1, PDZD2, S100A10 and many others. Interacts with NEDD4 and NEDD4L (By similarity).By similarity

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati116 – 404ICuratedAdd BLAST289
Repeati647 – 911IICuratedAdd BLAST265
Repeati1142 – 1451IIICuratedAdd BLAST310
Repeati1460 – 1759IVCuratedAdd BLAST300
Domaini1853 – 1882IQAdd BLAST30

Domaini

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.Curated

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Family and domain databases

InterProiView protein in InterPro
IPR005821. Ion_trans_dom.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
PANTHERiPTHR10037:SF263. PTHR10037:SF263. 1 hit.
PfamiView protein in Pfam
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PRINTSiPR00170. NACHANNEL.

Sequencei

Sequence statusi: Complete.

P0DMA5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEFPIGSVGT TNFRRFTPES LAEIEKQIAA HGAAKKARAK HGERKGQDEK
60 70 80 90 100
PRPQLDLKAC NQLPRFYGEL PAELVGEPLE DLDPFYSTHR TFMVLNKGRT
110 120 130 140 150
ISRFSATWAL WLFSPFNLIR RTAIKVSVHA WFSIFITITI LFNCVCMTQN
160 170 180 190 200
DLPEKIEYAF TVIYTFEALI KILARGFCLN EFTYLRDPWN WLDFSVITLA
210 220 230 240 250
YVGAAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI HSVRKLADVT
260 270 280 290 300
ILTVFCLSVF ALVGLQLFKG NLKNKCIKRS TDPHNAYNFS SQMADNFYIK
310 320 330 340 350
NGTTEPLLCG NGSDAGHCPS GYICLKTSDN PDFNYTSFDS FAWAFLSLFR
360 370 380 390 400
LMTQDSWERL YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE
410 420 430 440 450
EQNQATIAEI EAKEKKFQEA LEVLQKEQEV LAALGIDTTS LHSHNGSPLA
460 470 480 490 500
PKNANERKHR IKSRVSEGST DDNRSPQSDP YNQRRMSFLG LSSGRRRASH
510 520 530 540 550
SSVFHFRAPS QDVSFPDGIT DDGVFHGDHE SHRSSLLLAR GAGQAGPLPR
560 570 580 590 600
SPLASSPNPG PGHREEGQLT APTGELTTGA PEDLALEAAG QKKNFLSAEY
610 620 630 640 650
LNEPFRAQRA MSVVSIMTSV IEELEESKLR CPPCLINLAQ KYLIWECCPK
660 670 680 690 700
WMKFKMVLFE LVTDPFAELT ITLCIVVNTI FMAMEHYPMT DAFDAMLQAG
710 720 730 740 750
NIVFTVFFTM EMAFKIIAFD PYYYFQKKWN VFDCVIVTVS LLELSIAKKG
760 770 780 790 800
SLSVLRTFRL LRVFKLAKSW PTLNTLIKII GNSVGALGNL TFILAIIVFI
810 820 830 840 850
FALVGKQLLG EDYGCRKDGT ALWNEGQLRW HMCDFFHSFL VIFRILCGEW
860 870 880 890 900
IENMWVCMQV SEKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA
910 920 930 940 950
PEDDGEVNNL QVALARTQAF GQRASQAISS YFSSHCRLRW PKVGSQLGVK
960 970 980 990 1000
PSLTSSKAEH HITADAVNTA VGTSAKPALS GPKEDPRDFI TDANVWVSVP
1010 1020 1030 1040 1050
IAEGESDLDE LEEDIEQNSQ SSWREESPKG QQDQLWQIQR CEDHQVPNSP
1060 1070 1080 1090 1100
GSGMSSEDLA SYLGERWKSE ATPQVPAEGV DDTSSSEGST VDCPDPEEIL
1110 1120 1130 1140 1150
KKIPELADDL EEPDDCFTEG CTRHCPCCKV STSKFPWTTG WQVRKTCYRI
1160 1170 1180 1190 1200
VEHSWFESFI IFMILLSSGA LAFEDNYLEQ KPRVKSMLEY TDRVFTFIFV
1210 1220 1230 1240 1250
FEMLLKWVAY GFKKYFTNAW CWLDFLIVNI SLTSLIAKIL DYSDVASLKA
1260 1270 1280 1290 1300
LRTLRALRPL RALSRFEGMR VVVDALVGAI PSIMNVLLVC LIFWLIFSIM
1310 1320 1330 1340 1350
GVNLFAGKFS RCIDTSNNPF SVVNSTIVNN KSECRNQNHT GHFFWVNVKV
1360 1370 1380 1390 1400
NFDNVAMGYL ALLQVATFKG WMDIMYAAVD SREINSQPQW EDNLYMYLYF
1410 1420 1430 1440 1450
VVFIIFGGFF TLNLFVGVII DNFNQQKKKL GGQDIFMTEE QKKYYNAMKK
1460 1470 1480 1490 1500
LGSKKPQKPI PRPLNKYQGF VFDIVTRQAF DIIIMVLICL NMITMMVETD
1510 1520 1530 1540 1550
GQSEEKTKIL GRINQFFVAV FTGECVMKMF ALRQYYFTNG WNVFDFIVVI
1560 1570 1580 1590 1600
LSIGSLVFSA ILKSLESYFS PTLFRVIRLA RIGRILRLIR AAKGIRTLLF
1610 1620 1630 1640 1650
ALMMSLPALF NIGLLLFLVM FIYSIFGMAS FANVVEEAGI DDMFNFQTFG
1660 1670 1680 1690 1700
NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLSNNNTS KGNCGSPTVG
1710 1720 1730 1740 1750
IVFFTTYIII SFLIVVNMYI AVILENFNVA TEESTEPLSE DDFDMFYETW
1760 1770 1780 1790 1800
EKFDPEATQF IAFSALSDFA DTLSGPLRIP KPNQNILIQM DLPLVPGDKI
1810 1820 1830 1840 1850
HCLDILFAFT KNVLGESGEL DSLKTNMEEK FMATNLSKAS YEPIATTLRW
1860 1870 1880 1890 1900
KQEDISATVI QKAYRSYVLQ RSLTLSNPLR VPRAEDDDAP LPGEGYVTFM
1910 1920 1930 1940 1950
ANDSGRLPDK SETTSATSFP PSYDSVTRGL SDRVNISTSN SMHNEDEVTS

KEGDSPGPQ
Length:1,959
Mass (Da):220,523
Last modified:January 22, 2014 - v1
Checksum:iFE84EC9345B5EB74
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KF717604 mRNA. Translation: AHA38158.1.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSCNAA_ONYTO
AccessioniPrimary (citable) accession number: P0DMA5
Secondary accession number(s): U6BRW2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: January 22, 2014
Last modified: May 10, 2017
This is version 17 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  2. SIMILARITY comments
    Index of protein domains and families