Protein Details: Acid-sensing ion channel 1

Protein ID

ICDB_Pro_0695

Protein Name

Acid-sensing ion channel 1

Gene Name

ASIC1; ACCN2; BNAC2

Organism

Homo sapiens (Human)

Length

528 amino acids

AlphaFoldDB

AF-P78348-F1-model_v4.pdb

Function

Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel 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. Isoform 2 can also transport potassium;but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium 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. Isoform 1 does not display proton-gated cation channel activity.

Sequence

MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCVCTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNNRYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCSAEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETSFEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLDFFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEYCVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETIEQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSADKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC

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"; SITE 352: "Important for interaction with the spider venom psalmotoxin-1"; SITE 357: "Key residue for defining the pH sensitivity of ASIC1 (isoform 1)";

Disease

Chronic Rapidly Progressive Glomerulonephritis and Potocki-Lupski Syndrome

Location

Expressed in most or all neurons

DOI ID

10.1073/pnas.94.4.1459; 10.1074/jbc.m110.171330; 10.1038/nature04569; 10.1101/gr.2596504; 10.1016/s0896-6273(00)81144-7; 10.1042/0264-6021:3610443; 10.1074/jbc.m208995200; 10.1073/pnas.252782799; 10.1074/jbc.m407381200; 10.1074/jbc.m109.029009; 10.1038/nature11494; 10.1038/ncomms1917; 10.1016/j.neuropharm.2017.03.020

RefSeq

NP_001086.2 [P78348-2]; NP_001243759.1 [P78348-3]; NP_064423.2 [P78348-1]

Feature