ASIC1

This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

Full Name

Acid Sensing Ion Channel Subunit 1

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 Ca2+ entry into neurons upon acidosis. This Ca2+ 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 Ca2+ 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.

Biological Process

Associative learning Source: Ensembl
Behavioral fear response Source: Ensembl
Calcium ion transmembrane transport Source: Ensembl
Cellular response to pH Source: UniProtKB
Ion transmembrane transport Source: Reactome
Memory Source: Ensembl
Negative regulation of neurotransmitter secretion Source: Ensembl
Protein homotrimerization Source: UniProtKB
Regulation of membrane potential Source: Ensembl
Response to acidic pH Source: Ensembl
Response to amphetamine Source: Ensembl
Response to pH Source: ProtInc
Sensory perception of sour taste Source: UniProtKB
Signal transduction Source: ProtInc
Sodium ion transmembrane transport Source: UniProtKB
Sodium ion transport Source: UniProtKB

Cellular Location

Cell membrane. Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 (By similarity).

Topology

Cytoplasmic: 1-45 aa
Helical: 46-69 aa
Extracellular: 70-427 aa
Discontinuously helical: 428-454 aa
Cytoplasmic: 455-528 aa

PTM

Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel.