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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:P43681
Protein Name:Neuronal acetylcholine receptor subunit alpha-4
Length:627
Molecular Weight:69957.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate ions

Cross database links:

Drugbank: Drugbank Link   
Structure:
2LLY   5kxi     

External Searches:

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  • 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:	MELGGPGAPR LLPPLLLLLG TGLLRASSHV ETRAHAEERL LKKLFSGYNK WSRPVANISD 
61:	VVLVRFGLSI AQLIDVDEKN QMMTTNVWVK QEWHDYKLRW DPADYENVTS IRIPSELIWR 
121:	PDIVLYNNAD GDFAVTHLTK AHLFHDGRVQ WTPPAIYKSS CSIDVTFFPF DQQNCTMKFG 
181:	SWTYDKAKID LVNMHSRVDQ LDFWESGEWV IVDAVGTYNT RKYECCAEIY PDITYAFVIR 
241:	RLPLFYTINL IIPCLLISCL TVLVFYLPSE CGEKITLCIS VLLSLTVFLL LITEIIPSTS 
301:	LVIPLIGEYL LFTMIFVTLS IVITVFVLNV HHRSPRTHTM PTWVRRVFLD IVPRLLLMKR 
361:	PSVVKDNCRR LIESMHKMAS APRFWPEPEG EPPATSGTQS LHPPSPSFCV PLDVPAEPGP 
421:	SCKSPSDQLP PQQPLEAEKA SPHPSPGPCR PPHGTQAPGL AKARSLSVQH MSSPGEAVEG 
481:	GVRCRSRSIQ YCVPRDDAAP EADGQAAGAL ASRNTHSAEL PPPDQPSPCK CTCKKEPSSV 
541:	SPSATVKTRS TKAPPPHLPL SPALTRAVEG VQYIADHLKA EDTDFSVKED WKYVAMVIDR 
601:	IFLWMFIIVC LLGTVGLFLP PWLAGMI