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P0DMA5

- SCNAA_ONYTO

UniProt

P0DMA5 - SCNAA_ONYTO

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Protein
Sodium channel protein type 10 subunit alpha
Gene
Scn10a, Sns
Organism
Onychomys torridus (Southern grasshopper mouse)
Status
Reviewed - 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

GO - Molecular functioni

  1. voltage-gated sodium channel activity Source: InterPro

GO - Biological processi

  1. sensory perception of pain Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeNeotominaeOnychomys

Subcellular locationi

Membrane; Multi-pass membrane protein By similarity
Note: It can be translocated to the extracellular membrane through association with S100A10 By similarity.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei126 – 14924Helical; Name=S1 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei155 – 17420Helical; Name=S2 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei188 – 20619Helical; Name=S3 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei213 – 23220Helical; Voltage-sensor; Name=S4 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei249 – 27224Helical; Name=S5 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei373 – 39826Helical; Name=S6 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei660 – 68425Helical; Name=S1 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei696 – 71924Helical; Name=S2 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei728 – 74720Helical; Name=S3 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei754 – 77320Helical; Voltage-sensor; Name=S4 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei790 – 81021Helical; Name=S5 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei865 – 89026Helical; Name=S6 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei1150 – 117324Helical; Name=S1 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1187 – 121226Helical; Name=S2 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1219 – 124022Helical; Name=S3 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1245 – 126622Helical; Voltage-sensor; Name=S4 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1286 – 131328Helical; Name=S5 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1394 – 142027Helical; Name=S6 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1474 – 149724Helical; Name=S1 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1509 – 153224Helical; Name=S2 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1539 – 156224Helical; Name=S3 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1575 – 159622Helical; Voltage-sensor; Name=S4 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1612 – 163423Helical; Name=S5 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1700 – 172425Helical; Name=S6 of repeat IV; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. voltage-gated sodium channel complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi746 – 7472IA → TS: No effect on inhibition by the venom of Centruroides sculpturatus.
Mutagenesisi859 – 8591Q → E: Complete loss of inhibition by the venom of Centruroides sculpturatus; when associated with Q-862. 1 Publication
Mutagenesisi862 – 8621E → 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 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 19591959Sodium channel protein type 10 subunit alpha
PRO_0000424959Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi288 – 2881N-linked (GlcNAc...) Reviewed prediction
Glycosylationi311 – 3111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi334 – 3341N-linked (GlcNAc...) Reviewed prediction
Glycosylationi897 – 8971N-linked (GlcNAc...) Reviewed prediction
Modified residuei1453 – 14531Phosphoserine; by PKC By similarity

Post-translational modificationi

Ubiquitinated by NEDD4L; which promotes its endocytosis Inferred.
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.

Keywords - PTMi

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati125 – 399275I
Add
BLAST
Repeati659 – 891233II
Add
BLAST
Repeati1149 – 1421273III
Add
BLAST
Repeati1473 – 1725253IV
Add
BLAST
Domaini1853 – 188230IQ
Add
BLAST

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.

Sequence similaritiesi

Contains 1 IQ domain.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PANTHERiPTHR10037:SF23. PTHR10037:SF23. 1 hit.
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0DMA5-1 [UniParc]FASTAAdd to Basket

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MEFPIGSVGT TNFRRFTPES LAEIEKQIAA HGAAKKARAK HGERKGQDEK     50
PRPQLDLKAC NQLPRFYGEL PAELVGEPLE DLDPFYSTHR TFMVLNKGRT 100
ISRFSATWAL WLFSPFNLIR RTAIKVSVHA WFSIFITITI LFNCVCMTQN 150
DLPEKIEYAF TVIYTFEALI KILARGFCLN EFTYLRDPWN WLDFSVITLA 200
YVGAAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI HSVRKLADVT 250
ILTVFCLSVF ALVGLQLFKG NLKNKCIKRS TDPHNAYNFS SQMADNFYIK 300
NGTTEPLLCG NGSDAGHCPS GYICLKTSDN PDFNYTSFDS FAWAFLSLFR 350
LMTQDSWERL YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE 400
EQNQATIAEI EAKEKKFQEA LEVLQKEQEV LAALGIDTTS LHSHNGSPLA 450
PKNANERKHR IKSRVSEGST DDNRSPQSDP YNQRRMSFLG LSSGRRRASH 500
SSVFHFRAPS QDVSFPDGIT DDGVFHGDHE SHRSSLLLAR GAGQAGPLPR 550
SPLASSPNPG PGHREEGQLT APTGELTTGA PEDLALEAAG QKKNFLSAEY 600
LNEPFRAQRA MSVVSIMTSV IEELEESKLR CPPCLINLAQ KYLIWECCPK 650
WMKFKMVLFE LVTDPFAELT ITLCIVVNTI FMAMEHYPMT DAFDAMLQAG 700
NIVFTVFFTM EMAFKIIAFD PYYYFQKKWN VFDCVIVTVS LLELSIAKKG 750
SLSVLRTFRL LRVFKLAKSW PTLNTLIKII GNSVGALGNL TFILAIIVFI 800
FALVGKQLLG EDYGCRKDGT ALWNEGQLRW HMCDFFHSFL VIFRILCGEW 850
IENMWVCMQV SEKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA 900
PEDDGEVNNL QVALARTQAF GQRASQAISS YFSSHCRLRW PKVGSQLGVK 950
PSLTSSKAEH HITADAVNTA VGTSAKPALS GPKEDPRDFI TDANVWVSVP 1000
IAEGESDLDE LEEDIEQNSQ SSWREESPKG QQDQLWQIQR CEDHQVPNSP 1050
GSGMSSEDLA SYLGERWKSE ATPQVPAEGV DDTSSSEGST VDCPDPEEIL 1100
KKIPELADDL EEPDDCFTEG CTRHCPCCKV STSKFPWTTG WQVRKTCYRI 1150
VEHSWFESFI IFMILLSSGA LAFEDNYLEQ KPRVKSMLEY TDRVFTFIFV 1200
FEMLLKWVAY GFKKYFTNAW CWLDFLIVNI SLTSLIAKIL DYSDVASLKA 1250
LRTLRALRPL RALSRFEGMR VVVDALVGAI PSIMNVLLVC LIFWLIFSIM 1300
GVNLFAGKFS RCIDTSNNPF SVVNSTIVNN KSECRNQNHT GHFFWVNVKV 1350
NFDNVAMGYL ALLQVATFKG WMDIMYAAVD SREINSQPQW EDNLYMYLYF 1400
VVFIIFGGFF TLNLFVGVII DNFNQQKKKL GGQDIFMTEE QKKYYNAMKK 1450
LGSKKPQKPI PRPLNKYQGF VFDIVTRQAF DIIIMVLICL NMITMMVETD 1500
GQSEEKTKIL GRINQFFVAV FTGECVMKMF ALRQYYFTNG WNVFDFIVVI 1550
LSIGSLVFSA ILKSLESYFS PTLFRVIRLA RIGRILRLIR AAKGIRTLLF 1600
ALMMSLPALF NIGLLLFLVM FIYSIFGMAS FANVVEEAGI DDMFNFQTFG 1650
NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLSNNNTS KGNCGSPTVG 1700
IVFFTTYIII SFLIVVNMYI AVILENFNVA TEESTEPLSE DDFDMFYETW 1750
EKFDPEATQF IAFSALSDFA DTLSGPLRIP KPNQNILIQM DLPLVPGDKI 1800
HCLDILFAFT KNVLGESGEL DSLKTNMEEK FMATNLSKAS YEPIATTLRW 1850
KQEDISATVI QKAYRSYVLQ RSLTLSNPLR VPRAEDDDAP LPGEGYVTFM 1900
ANDSGRLPDK SETTSATSFP PSYDSVTRGL SDRVNISTSN SMHNEDEVTS 1950
KEGDSPGPQ 1959
Length:1,959
Mass (Da):220,523
Last modified:January 22, 2014 - v1
Checksum:iFE84EC9345B5EB74
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
KF717604 mRNA. Translation: AHA38158.1.

Cross-referencesi

Web resourcesi

Protein Spotlight

A pain soothed - Issue 157 of January 2014

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
KF717604 mRNA. Translation: AHA38158.1 .

3D structure databases

ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 1.20.120.350. 4 hits.
InterProi IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view ]
PANTHERi PTHR10037:SF23. PTHR10037:SF23. 1 hit.
Pfami PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view ]
PRINTSi PR00170. NACHANNEL.
SMARTi SM00015. IQ. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin."
    Rowe A.H., Xiao Y., Rowe M.P., Cummins T.R., Zakon H.H.
    Science 342:441-446(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF 746-ILE-ALA-747; GLN-859 AND GLU-862.

Entry informationi

Entry nameiSCNAA_ONYTO
AccessioniPrimary (citable) accession number: P0DMA5
Secondary accession number(s): U6BRW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: January 22, 2014
Last modified: September 3, 2014
This is version 7 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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 (1 Publication).

Documents

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

External Data

Dasty 3

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