Reviewed,
UniProtKB/Swiss-Prot Q15858 (SCN9A_HUMAN)
Last modified
November 25, 2008.
Version 75.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (6) |
 Third-party data |
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Names and origin
| Protein names | Recommended name: Sodium channel protein type 9 subunit alpha Alternative name(s): Sodium channel protein type IX subunit alpha Voltage-gated sodium channel subunit alpha Nav1.7 Neuroendocrine sodium channel Short name=hNE-Na Peripheral sodium channel 1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1988 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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 Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain By similarity. |
| Subunit structure | The sodium channel consists of a large polypeptide and 2-3 smaller ones. This sequence represents a large polypeptide. Interacts with NEDD4 and NEDD4L By similarity. |
| Subcellular location | Membrane; Multi-pass membrane protein. Note= In neurite terminals By similarity. |
| Tissue specificity | Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body, smooth muscle cells, MTC cell line and C-cell carcinoma. Isoform 1 is expressed preferentially in the central and peripheral nervous system while isoform 2 is expressed preferentially in the dorsal root ganglion. |
| Domain | 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. |
| Post-translational modification | Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4 By similarity. |
| Involvement in disease | Defects in SCN9A are the cause of primary erythermalgia [MIM:133020]. It is an autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. Defects in SCN9A are the cause of autosomal recessive congenital indifference to pain [MIM:243000]; also known as channelopathy-associated insensitivity to pain. Affected individuals have a congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. Defects in SCN9A are a cause of paroxysmal extreme pain disorder (PEPD) [MIM:167400]; previously known as familial rectal pain (FRP). PEPD is an autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing. |
| Sequence similarities | Belongs to the sodium channel family. Contains 1 IQ domain. |
Ontologies
Keywords | |
|---|---|
| Biological process | Ion transport Sodium transport Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Domain | Repeat Transmembrane |
| Ligand | Sodium |
| Molecular function | Ionic channel Sodium channel Voltage-gated channel |
| PTM | Glycoprotein Phosphoprotein Ubl conjugation |
Gene Ontology (GO) | |
| Biological process | sodium ion transport Ref.1 Traceable author statement. Source: ProtInc |
| Cellular component | voltage-gated sodium channel complex Inferred from electronic annotation. Source: InterPro |
| Molecular function | sodium ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated sodium channel activity Ref.1Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q15858-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q15858-2) The sequence of this isoform differs from the canonical sequence as follows: 200-229: YLTEFVNLGNVSALRTFRVLRALKTISVIP → YVTEFVDLGNVSALRTFRVLRALKTISVIP | ||||||
| Isoform 3 (identifier: Q15858-3) The sequence of this isoform differs from the canonical sequence as follows: 648-658: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1988 | 1988 | Sodium channel protein type 9 subunit alpha | PRO_0000048502 | |||||
Regions | |||||||||
| Transmembrane | 122 – 145 | 24 | S1 of repeat I By similarity | ||||||
| Transmembrane | 154 – 173 | 20 | S2 of repeat I By similarity | ||||||
| Transmembrane | 187 – 205 | 19 | S3 of repeat I By similarity | ||||||
| Transmembrane | 212 – 231 | 20 | S4 of repeat I By similarity | ||||||
| Transmembrane | 248 – 271 | 24 | S5 of repeat I By similarity | ||||||
| Transmembrane | 379 – 404 | 26 | S6 of repeat I By similarity | ||||||
| Transmembrane | 739 – 763 | 25 | S1 of repeat II By similarity | ||||||
| Transmembrane | 775 – 798 | 24 | S2 of repeat II By similarity | ||||||
| Transmembrane | 807 – 826 | 20 | S3 of repeat II By similarity | ||||||
| Transmembrane | 833 – 852 | 20 | S4 of repeat II By similarity | ||||||
| Transmembrane | 869 – 889 | 21 | S5 of repeat II By similarity | ||||||
| Transmembrane | 943 – 968 | 26 | S6 of repeat II By similarity | ||||||
| Transmembrane | 1188 – 1211 | 24 | S1 of repeat III By similarity | ||||||
| Transmembrane | 1225 – 1250 | 26 | S2 of repeat III By similarity | ||||||
| Transmembrane | 1257 – 1278 | 22 | S3 of repeat III By similarity | ||||||
| Transmembrane | 1283 – 1304 | 22 | S4 of repeat III By similarity | ||||||
| Transmembrane | 1324 – 1351 | 28 | S5 of repeat III By similarity | ||||||
| Transmembrane | 1431 – 1457 | 27 | S6 of repeat III By similarity | ||||||
| Transmembrane | 1511 – 1534 | 24 | S1 of repeat IV By similarity | ||||||
| Transmembrane | 1546 – 1569 | 24 | S2 of repeat IV By similarity | ||||||
| Transmembrane | 1576 – 1599 | 24 | S3 of repeat IV By similarity | ||||||
| Transmembrane | 1610 – 1631 | 22 | S4 of repeat IV By similarity | ||||||
| Transmembrane | 1647 – 1669 | 23 | S5 of repeat IV By similarity | ||||||
| Transmembrane | 1736 – 1760 | 25 | S6 of repeat IV By similarity | ||||||
| Repeat | 121 – 405 | 285 | I | ||||||
| Repeat | 738 – 969 | 232 | II | ||||||
| Repeat | 1187 – 1458 | 272 | III | ||||||
| Repeat | 1510 – 1761 | 252 | IV | ||||||
| Domain | 1889 – 1918 | 30 | IQ | ||||||
Amino acid modifications | |||||||||
| Modified residue | 1413 | 1 | Phosphotyrosine | ||||||
| Modified residue | 1418 | 1 | Phosphoserine | ||||||
| Glycosylation | 209 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 283 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 1352 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 1366 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 1375 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 200 – 229 | 30 | YLTEF…ISVIP → YVTEFVDLGNVSALRTFRVL RALKTISVIP in isoform 2. | VSP_012028 | |||||
| Alternative sequence | 648 – 658 | 11 | Missing in isoform 3. | VSP_012029 | |||||
| Natural variant | 241 | 1 | S → T in primary erythermalgia. | VAR_032014 | |||||
| Natural variant | 859 | 1 | I → T in primary erythermalgia; sporadic; activated at more negative potentials; slower inactivation kinetics than wild-type channels. | VAR_019947 | |||||
| Natural variant | 869 | 1 | L → H in primary erythermalgia; activated at more negative potentials; slower inactivation kinetics than wild-type channels. | VAR_019948 | |||||
| Natural variant | 932 | 1 | M → L: dbSNP rs12478318. | VAR_030444 | |||||
| Natural variant | 1007 | 1 | R → C in PEPD. | VAR_032015 | |||||
| Natural variant | 1161 | 1 | R → W: dbSNP rs6746030. | VAR_019949 | |||||
| Natural variant | 1309 | 1 | V → D in PEPD. | VAR_032016 | |||||
| Natural variant | 1309 | 1 | V → F in PEPD. | VAR_032017 | |||||
| Natural variant | 1310 | 1 | V → F in PEPD. | VAR_032018 | |||||
| Natural variant | 1460 | 1 | F → V in primary erythermalgia; produces a hyperpolarizing shift in channel activation and a depolarizing shift in steady-state activation. | VAR_032019 | |||||
| Natural variant | 1472 | 1 | I → T in PEPD; reduction in fast inactivation leading to persistent sodium current. | VAR_032020 | |||||
| Natural variant | 1473 | 1 | F → V in PEPD. | VAR_032021 | |||||
| Natural variant | 1475 | 1 | T → I in PEPD; reduction in fast inactivation leading to persistent sodium current. | VAR_032022 | |||||
| Natural variant | 1638 | 1 | M → K in PEPD; reduction in fast inactivation leading to persistent sodium current. | VAR_032023 | |||||
| Natural variant | 1919 | 1 | D → G: dbSNP rs3750904. | VAR_019950 | |||||
Experimental info | |||||||||
| Sequence conflict | 201 | 1 | L → V in AAT85835 and AAT85833. Ref.2 | ||||||
| Sequence conflict | 206 | 1 | N → D in AAT85835 and AAT85833. Ref.2 | ||||||
| Sequence conflict | 267 | 1 | F → S in AAT85834. Ref.2 | ||||||
| Sequence conflict | 301 | 1 | K → R in AAT85835. Ref.2 | ||||||
| Sequence conflict | 309 | 1 | S → P in AAT85834. Ref.2 | ||||||
| Sequence conflict | 420 | 1 | E → G in AAT85834. Ref.2 | ||||||
| Sequence conflict | 430 | 1 | L → P in AAT85834. Ref.2 | ||||||
| Sequence conflict | 501 | 1 | S → P in AAT85835. Ref.2 | ||||||
| Sequence conflict | 610 | 1 | P → T in AAT85835. Ref.2 | ||||||
| Sequence conflict | 642 | 1 | G → R in AAT85835. Ref.2 | ||||||
Sequences
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