CHRNA4
entrez
1137
canonical
uniprot
P43681
canonical
ensembl
ENSG00000101204
resolver
ensp
ENSP00000359285
resolver
genesymbol
CHRNA4
resolver
genesymbol_syn
NACRA4
resolver
hgnc
HGNC:1958
resolver
uniprot
B4DK78
resolver
uniprot
Q4JGR7
resolver
uniprot
Q4VAQ3
resolver
uniprot
Q4VAQ5
resolver
uniprot
Q4VAQ6
resolver
uniprot
Q59FV0
resolver
uniprot_entry
ACHA4_HUMAN
resolver
uniprot_entry
B4DK78_HUMAN
resolver
uniprot_entry
Q4VAQ3_HUMAN
resolver
uniprot_entry
Q59FV0_HUMAN
resolver
uniprot_sec
Q4JGR7
resolver
uniprot_sec
Q4VAQ5
resolver
uniprot_sec
Q4VAQ6
resolver
activity_regulation
ACTIVITY REGULATION: Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:12527804, PubMed:16835356, PubMed:17132685, PubMed:20881005, PubMed:27698419, PubMed:29720657, PubMed:38454578). Channel potentiation by calcium is stoichiometry-selective, CHRNA4:CHRNB2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the CHRNA4 subunit and between the CHRNA4 and CHRNB2 subunits (PubMed:38454578). nAChR activity is inhibited by the antagonist alpha-conotoxins BuIA, PnIA, GID and MII, small disulfide-constrained peptides from cone snails (By similarity). {ECO:0000250|UniProtKB:P09483, ECO:0000269|PubMed:12527804, ECO:0000269|PubMed:16835356, ECO:0000269|PubMed:17132685, ECO:0000269|PubMed:20881005, ECO:0000269|PubMed:27698419, ECO:0000269|PubMed:29720657, ECO:0000269|PubMed:38454578}.
uniprot
proteins
amino_acid_sequence
MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKLFSGYNKWSRPVANISDVVLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIRIPSELIWRPDIVLYNNADGDFAVTHLTKAHLFHDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTMKFGSWTYDKAKIDLVNMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFVIRRLPLFYTINLIIPCLLISCLTVLVFYLPSECGEKITLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPRTHTMPTWVRRVFLDIVPRLLLMKRPSVVKDNCRRLIESMHKMASAPRFWPEPEGEPPATSGTQSLHPPSPSFCVPLDVPAEPGPSCKSPSDQLPPQQPLEAEKASPHPSPGPCRPPHGTQAPGLAKARSLSVQHMSSPGEAVEGGVRCRSRSIQYCVPRDDAAPEADGQAAGALASRNTHSAELPPPDQPSPCKCTCKKEPSSVSPSATVKTRSTKAPPPHLPLSPALTRAVEGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLFLPPWLAGMI
uniprot
proteins
disease_involvement
DISEASE: Epilepsy, nocturnal frontal lobe, 1 (ENFL1) [MIM:600513]: An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. {ECO:0000269|PubMed:10563623, ECO:0000269|PubMed:14623738, ECO:0000269|PubMed:7550350}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). CHRNA4 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, as well as CHRNA5 and CHRNB3 as accesory subunits. Is the most abundant nAChR subtype expressed in the central nervous system (PubMed:16835356, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:27698419, PubMed:29720657, PubMed:38454578). Involved in the modulation of calcium-dependent signaling pathways, influences the release of neurotransmitters, including dopamine, glutamate and GABA (By similarity). {ECO:0000250|UniProtKB:O70174, ECO:0000269|PubMed:16835356, ECO:0000269|PubMed:22361591, ECO:0000269|PubMed:27698419, ECO:0000269|PubMed:29720657, ECO:0000269|PubMed:38454578}.
uniprot
proteins
mass_dalton
69957
uniprot
proteins
mutagenesis
MUTAGEN 75; /note="D->A: Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations."; /evidence="ECO:0000269|PubMed:38454578"; MUTAGEN 78; /note="E->A: Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations."; /evidence="ECO:0000269|PubMed:38454578"; MUTAGEN 205; /note="E->A: Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations."; /evidence="ECO:0000269|PubMed:38454578"; MUTAGEN 208; /note="E->A: Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations."; /evidence="ECO:0000269|PubMed:38454578"; MUTAGEN 224; /note="E->A: Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations."; /evidence="ECO:0000269|PubMed:38454578"; MUTAGEN 294; /note="E->K: Loss of CA(2+) permeability."; /evidence="ECO:0000269|PubMed:17132685
uniprot
proteins
protein_family
Acetylcholine receptor (TC 1.A.9.1) subfamily
uniprot
proteins
protein_family
Alpha-4/CHRNA4 sub-subfamily
uniprot
proteins
protein_family
Ligand-gated ion channel (TC 1.A.9) family
uniprot
proteins
pubmed
10563623
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12527804
uniprot
proteins
pubmed
14623738
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16120769
uniprot
proteins
pubmed
16835356
uniprot
proteins
pubmed
17132685
uniprot
proteins
pubmed
20881005
uniprot
proteins
pubmed
22361591
uniprot
proteins
pubmed
27344019
uniprot
proteins
pubmed
27698419
uniprot
proteins
pubmed
29720657
uniprot
proteins
pubmed
38454578
uniprot
proteins
pubmed
7550350
uniprot
proteins
pubmed
7721089
uniprot
proteins
pubmed
8833159
uniprot
proteins
pubmed
8906617
uniprot
proteins
pubmed
9009220
uniprot
proteins
sequence_length
627
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Synaptic cell membrane {ECO:0000250|UniProtKB:O70174}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:O70174}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 250..269; /note="Helical"; /evidence="ECO:0000269|PubMed:29720657, ECO:0007744|PDB:6CNJ"; TRANSMEM 275..291; /note="Helical"; /evidence="ECO:0000269|PubMed:29720657, ECO:0007744|PDB:6CNJ"; TRANSMEM 306..330; /note="Helical"; /evidence="ECO:0000269|PubMed:29720657, ECO:0007744|PDB:6CNJ"; TRANSMEM 601..619; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins