Protein Details: Acid-sensing ion channel 1
Protein ID
ICDB_Pro_0624
Protein Name
Acid-sensing ion channel 1
Gene Name
Asic1; Accn2; Bnac2
Organism
Rattus norvegicus (Rat)
Length
526 amino acids
AlphaFoldDB
AF-P55926-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. Isoform 3 discrimates stronger than isoform 1 between monovalent cations. Isoform 3 can flux Ca(2+) while isoform 1 cannot. Heteromeric channels composed of isoform 2 and isoform 3 are active but have a lower pH-sensitivity. 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.
Sequence
PDB Structures
Ligand Binding
Binding Site
SITE 71: "Important for channel gating"; SITE 79: "Important for channel desensitizing"; SITE 175: "Important residue in interaction with the spider venom Pi-theraphotoxin-Hm3a; which can explain functional difference between ASIC1a and ASIC1b";SITE 177: "Important residue for interaction with the spider venom Pi-theraphotoxin-Hm3a; which can explain functional difference between ASIC1a and ASIC1b";SITE 287: "Important for channel gating"; SITE 349: "Important for interaction with the snake venom mambalgin-2"; SITE 350: "Important for interaction with the snake venom mambalgin-1 and mambalgin-2 toxins; probably binds to its residue L-53; Important for interaction with the spider venom Pi-hexatoxin-Hi1a and psalmotoxin-1"
Disease
Location
Expressed in dorsal root ganglia and sciatic nerve (at protein level). Widely distributed throughout the brain. Expressed in olfactory bulb; neo and allocortical regions; dentate granule cells; pyramidal cells of CA1-CA3 subfields of the hippocampal formation; habenula; basolateral amygdaloid nuclei; and in the Purkinje and granule cells of the cerebellum. Expressed in olfactory bulb; neo and allocortical regions; dentate granule cells; pyramidal cells of CA1-CA3 subfields of the hippocampal formation; habenula; basolateral amygdaloid nuclei; and in the Purkinje and granule cells of the cerebellum. Expressed in olfactory bulb; neo and allocortical regions; dentate granule cells; pyramidal cells of CA1-CA3 subfields of the hippocampal formation; habenula; basolateral amygdaloid nuclei; and in the Purkinje and granule cells of the cerebellum. Diffusely detected over most other regions of the basal ganglia; including thalamic nuclei; substantia nigra; striatum and globus pallidus; hypothalamus; midbrain; pons; medulla and choroid plexus. Isoform 3 is expressed only in dorsal root ganglion (DRG) while isoform 1 is expressed in DRG; spinal chord; trigeminal ganglia and the trigeminal mesencephalic nucleus.
DOI ID
10.1038/386173a0; 10.1073/pnas.95.17.10240; 10.1074/jbc.m104030200; 10.1097/00001756-200109170-00022; 10.1074/jbc.272.46.28819; 10.1074/jbc.m003643200; 10.1016/s0896-6273(00)81144-7; 10.1523/jneurosci.21-20-08026.2001; 10.1074/jbc.m205877200; 10.1073/pnas.042688199; 10.1074/jbc.m304441200; 10.1016/j.cell.2004.08.026; 10.1085/jgp.200308973; 10.1038/nature11494; 10.1016/j.toxicon.2013.04.008; 10.1002/anie.201308898; 10.1074/jbc.m114.561076; 10.1111/bph.13267; 10.1074/jbc.m115.702373; 10.1016/j.neuropharm.2017.03.020; 10.1073/pnas.1614728114
RefSeq
NP_077068.1 [P55926-1]; XP_006257440.1 [P55926-3]