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nicotinic receptor alpha-7, neuronal acetylcholine receptor subunit alpha-7 (CHRNA7, NACHRA7, alpha 7 nAChR)

Function: - nicotinic receptor alpha subunit - selectively bound by alpha-bungarotoxin. [5] the channel is blocked by alpha-bungarotoxin - interaction with RIC3 is required for proper folding & assembly - forms functional homopentamers, ligand-gated ion channels linked to rapidly desensitizing Ca2+ influx. [4] - diminishes phagocyte (microglia, macrophage) inflammatory response on binding of acetylcholine or nicotine - role in modulation of release of several neurotransmitters, mediating &/or modulating synaptic transmission, plasticity, & neurodegeneration (putative) [5] - postsynaptically, CHRNA7 may undergo dynamic regulation, with insertion into the synapse & subsequent internalization [5] - stimulation of CHRNA7 transduces signals to phosphatidylinositol 3-kinase & Akt, via Janus kinase 2 (JAK2) Structure: - homopentamer - belongs to the ligand-gated ionic channel (TC 1.A.9) family - mass spec: mass=54157.68; method=MALDI; Range=23-502 [8] Compartment: - cell junction, synapse, postsynaptic cell membrane - present in both presynaptic & postsynaptic membranes Alternative splicing: named isoforms=3 Expression: - present on macrophages in the periphery & microglia in the CNS - widely expressed throughout the mammalian brain [4] - present at nearly all synapses in CA1 stratum radiatum - GABAergic & glutamatergic synapses bear alpha7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum Pathology: - stimulation of CHRNA7 may result in neuroprotection from the toxicity of the amyloid beta-peptide via signals from phosphatidylinositol 3-kinase & Akt, via Janus kinase 2 (JAK2) [4] Comparative biology: - a segmental duplication of chromosome 15 involving CHRNA7 & Fam7A is one of the few features distinguishing the human genome from the chimpanzee genome [6,7]

Related

CHRNA7 (nicotinic receptor alpha-7) gene

General

evolutionary divergent human protein nicotinic receptor alpha oligomerizing protein

Properties

SIZE: entity length = 502 aa MW = 56 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {1-230} MOTIF: signal sequence {1-22} N-glycosylation site {N46} N-glycosylation site {N90} N-glycosylation site {N133} cysteine residue {C150} MODIFICATION: cysteine residue {C164} cysteine residue {C164} MODIFICATION: cysteine residue {C150} cysteine residue {C212} MODIFICATION: cysteine residue {C213} cysteine residue {C213} MODIFICATION: cysteine residue {C212} transmembrane domain {231-255} cytoplasmic loop {256-261} transmembrane domain {262-280} exoplasmic loop {281-295} transmembrane domain {296-317} cytoplasmic loop {318-469} transmembrane domain {470-490} exoplasmic domain {491-2502}

Database Correlations

OMIM 118511 UniProt P36544 PFAM correlations LOCUS-LINK correlations KEGG correlations

References

  1. UniProt :accession P36544
  2. Entrez Gene :accession 1139
  3. Chemical & Engineering News, March 27, 2004 pg 8 Wang H et al Nature 421:384, 2001 PMID: 12508119 J Tan & RD Shytle, J Neurochem (Mar 8) http://www.blackwell-synergy.com/links/doi/10.1046/j.1471-4159.2004.02347.x
  4. Shaw S, Bencherif M, Marrero MB. Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Abeta-(1-42) amyloid. J Biol Chem. 2002 Nov 22;277(47):44920-4. Epub 2002 Sep 18. PMID: 12244045
  5. Fabian-Fine R, Skehel P, Errington ML, Davies HA, Sher E, Stewart MG, Fine A. Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001 Oct 15;21(20):7993-8003. PMID: 11588172
  6. Riley B, Williamson M, Collier D, Wilkie H, Makoff A. A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13-q14. Genomics. 2002 Feb;79(2):197-209. PMID: 11829490
  7. Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L, Brenton M, Hink R, Burgers S, Hernandez-Boussard T, Karimpour- Fard A, Glueck D, McGavran L, Berry R, Pollack J, Sikela JM. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2004 Jul;2(7):E207. Epub 2004 Jul 13. PMID: 15252450
  8. Mass spec data PMID: 11840567
  9. PMID: 16120769