Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

SCN1A (P35498) - Overview - Molecular Target Synopsis

Protein


SCN1A, Sodium channel protein type 1 subunit alpha
UniProt P35498

Also Known as SCN1A_HUMAN, SCN1A, NAC1, SCN1

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. Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli. The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B). Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with FGF13 (PubMed:21566136). Interacts with SCN1B (PubMed:17928445, PubMed:15525788). Interacts with the conotoxin GVIIJ (PubMed:24497506). Interacts with the spider beta/delta-theraphotoxin-Pre1a (PubMed:28428547).

Isoforms / Transcripts (Protein Coding)


Drugs


SCN1A is targeted by Approved Drugs Riluzole, Indecainide, Lidocaine, Phenazopyridine, Alkavervir, Propoxycaine, Dronedarone, Levobupivacaine, Tocainide, Oxcarbazepine, Hexylcaine, Eslicarbazepine, Topiramate, Bupivacaine, Prilocaine, Ethotoin, Etidocaine, Eslicarbazepine Acetate, Dyclonine, Veratrum Viride Root, Ropivacaine, Quinidine Sulfate, Merethoxylline Procaine, Lamotrigine, Quinidine, Phenacemide, Propafenone, Benoxinate, Mepivacaine, Tetracaine, Procaine Benzylpenicillin, Articaine, Procaine, Phenytoin, Mephenytoin, Fosphenytoin, Chloroprocaine, Proparacaine, Mexiletine, Rufinamide, Disopyramide, Orphenadrine, Carbamazepine. (see details)
Riluzole
Indecainide
Lidocaine
Phenazopyridine
Alkavervir
Propoxycaine
Dronedarone
Levobupivacaine
Tocainide
Oxcarbazepine
Hexylcaine
Eslicarbazepine
Topiramate
Bupivacaine
Prilocaine
Ethotoin
Etidocaine
Eslicarbazepine Acetate
Dyclonine
Veratrum Viride Root
Ropivacaine
Quinidine Sulfate
Merethoxylline Procaine
Lamotrigine
Quinidine
Phenacemide
Propafenone
Benoxinate
Mepivacaine
Tetracaine
Procaine Benzylpenicillin
Articaine
Procaine
Phenytoin
Mephenytoin
Fosphenytoin
Chloroprocaine
Proparacaine
Mexiletine
Rufinamide
Disopyramide
Orphenadrine
Carbamazepine

Sub-cellular localization


UniProt: SCN1A is active in the following subcellular-locations: cell membrane.
GO terms: SCN1A is active in the following subcellular-locations: axon, axon initial segment, intercalated disc, neuronal cell body, node of Ranvier, nuclear body, nucleoplasm, plasma membrane, T-tubule, voltage-gated sodium channel complex, Z disc.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project SCN1A has gain in 1 cell-lines, loss in 2 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, CAKI_1, TK_10

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1882, COR-L47, C3A

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


At greater than 90% identity similarity to SCN1A there are:
2 structures (2 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


SCN1A has been screened with 319 compounds (563 bioactivities), 13 compounds have bioactivities that show binding affinity of <= 500nM (17 bioactivities). (see details)