amiloride-sensitive cation channel 2, neuronal; acid-sensing ion channel 1; ASIC1; brain Na+ channel 2; BNaC2 (ACCN2, ASIC1, BNAC2)

Function: - cation channel with high affinity for Na⁺ - gated by extracellular protons - inhibited by the diuretic amiloride - also permeable for Ca⁺², Li⁺ & K⁺ - generates a biphasic current with a fast inactivating & a slow sustained phase - mediates glutamate-independent Ca⁺² entry into neurons upon acidosis; this Ca⁺² overloading is toxic for cortical neurons & 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 & CaM kinase 2 phosphorylation & thereby the density of dendritic spines - modulates activity in the circuits underlying innate fear (putative) - phosphorylation by PKA regulates interaction with PRKCABP & subcellular location - phosphorylation by PKC may regulate the channel - homotetramer or heterotetramer with other ASIC proteins (probable) - interacts with STOM & ACCN1 (putative) - interacts with PRKCABP Structure: - belongs to the amiloride-sensitive Na⁺ channel family Compartment: - cell membrane; multi-pass membrane protein (putative) - localizes in synaptosomes at dendritic synapses of neurons - colocalizes with DLG4 (putative) Alternative splicing: named isoforms=2 Expression: - expressed in most or all neurons Notes: - potentiated by Ca⁺², Mg⁺², Ba⁺² & multivalent cations - inhibited by anti-inflammatory drugs including salicylic acid (putative) - potentiated by FMRFamide-related neuropeptides - pH dependence may be regulated by serine proteases Comparative biology: - the splice variant from ASIC1a described in mouse & rat, which gives rise to an isoform with different N-termini (Asic1b), does not seem to exist in human

General

amiloride-sensitive cation channel evolutionary divergent protein Na+ channel phosphoprotein transmembrane 2 protein

Properties

SIZE: entity length = 528 aa MW = 60 kD COMPARTMENT: plasma membrane MOTIF: cytoplasmic domain {1-44} transmembrane domain {45-65} exoplasmic loop {66-427} MOTIF: N-glycosylation site {N368} N-glycosylation site {N395} transmembrane domain {428-448} cytoplasmic domain {449-528} MOTIF: Ser phosphorylation site {S479} ION-PERMEABILITY: Na+

Database Correlations

OMIM 602866 UniProt P78348 Pfam PF00858 Entrez Gene 41 Kegg hsa:41

References

UniProt :accession P78348