Protein Details: Acid-sensing ion channel 1

Protein ID

ICDB_Pro_1091

Protein Name

Acid-sensing ion channel 1

Gene Name

Asic1; Accn2; Asic; Bnac2

Organism

Mus musculus (Mouse)

Length

526 amino acids

AlphaFoldDB

AF-Q6NXK8-F1-model_v4.pdb

Function

Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions; but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.

Sequence

MELKTEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCVCTERVQYYFCYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNNRYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEACSAEDFKVVFTRYGKCYTFNSGQDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETSFEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVSCQEQRLIYLPSPWGTCNAVTMDSDFFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEYCVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETIEQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHRLCRRGKCQKEAKRNSADKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

SITE 71: "Important for channel gating"; SITE 79: "Important for channel desensitizing"; SITE 287: "Important for channel gating"

Disease

Location

Expressed in brain areas receiving strong excitatory corticofugal input. In hippocampus; expressed in the hilus of the dentate gyrus. In the cerebral cortex expressed in anterior and posterior cingulate cortex; sensory and motor cortices. In the cerebral cortex expressed in anterior and posterior cingulate cortex; sensory and motor cortices. In the cerebral cortex expressed in anterior and posterior cingulate cortex; sensory and motor cortices. In the sensory cortex strongest expression is detected in the whisker barrel field. In sensorimotor and cingulate cortex expression is elevated in layer III. Also expressed in basal ganglia; striatum; ventral pallidum; olfactory tubercle; and nucleus accumbens. Weakly expressed in thalamus with the exception of the habenula and the medial septal nuclei. In olfactory bulb; preferentially expressed in the glomerular layer; within glomeruli. Expressed in cerebellum in the molecular and granule cell layers. Strongly expressed in amygdala complex; particularly in the lateral and basolateral nuclei. Isoform 1 is more abundant in brain compared to isoform 2 (at protein level). Expressed in the nodose ganglion and dorsal root ganglion

DOI ID

10.1101/gr.2596504; 10.1016/s0896-6273(02)00661-x; 10.1523/jneurosci.23-13-05496.2003; 10.1016/j.cell.2004.08.026; 10.1053/j.gastro.2004.08.061; 10.1074/jbc.m407708200; 10.1073/pnas.0608018103; 10.1016/j.biopsych.2007.05.008; 10.1016/j.cell.2010.12.001

RefSeq

NP_001276720.1 [Q6NXK8-2]; NP_033727.1 [Q6NXK8-1]