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1.A.9.1.6
The α4β2 nicotinic acetylcholine receptor. The NMR structure of the transmembrane domain and the multiple anaesthetic binding sites are known (Bondarenko et al., 2012).  Mutations cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; Díaz-Otero et al. 2000).
Nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery. This system contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders, i.e., schizophrenia and Alzheimer's disease. It provides an extra layer of molecular complexity by existing in two different stoichiometries determined by the subunit composition. By potentiating the action of an agonist through binding to an allosteric site, positive allosteric modulators can enhance cholinergic neurotransmission (Grupe et al. 2015). Most pentameric receptors are heteromeric. Morales-Perez et al. 2016 presented the X-ray crystallographic structure of the human α4β2 nicotinic receptor, the most abundant nicotinic subtype in the brain. The side chains of alpha4 L257 (9') and alpha4L264 (16') may beresponsible for the main constrictions in the transmembrane pore (Yu et al. 2019).

Accession Number:P17787
Protein Name:Neuronal acetylcholine receptor subunit beta-2
Length:502
Molecular Weight:57019.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate ions

Cross database links:

Drugbank: Drugbank Link   
Structure:
2K58   2K59   2KSR   2LM2   5kxi     

External Searches:

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  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MARRCGPVAL LLGFGLLRLC SGVWGTDTEE RLVEHLLDPS RYNKLIRPAT NGSELVTVQL 
61:	MVSLAQLISV HEREQIMTTN VWLTQEWEDY RLTWKPEEFD NMKKVRLPSK HIWLPDVVLY 
121:	NNADGMYEVS FYSNAVVSYD GSIFWLPPAI YKSACKIEVK HFPFDQQNCT MKFRSWTYDR 
181:	TEIDLVLKSE VASLDDFTPS GEWDIVALPG RRNENPDDST YVDITYDFII RRKPLFYTIN 
241:	LIIPCVLITS LAILVFYLPS DCGEKMTLCI SVLLALTVFL LLISKIVPPT SLDVPLVGKY 
301:	LMFTMVLVTF SIVTSVCVLN VHHRSPTTHT MAPWVKVVFL EKLPALLFMQ QPRHHCARQR 
361:	LRLRRRQRER EGAGALFFRE APGADSCTCF VNRASVQGLA GAFGAEPAPV AGPGRSGEPC 
421:	GCGLREAVDG VRFIADHMRS EDDDQSVSED WKYVAMVIDR LFLWIFVFVC VFGTIGMFLQ 
481:	PLFQNYTTTT FLHSDHSAPS SK