ASIC4 Membrane Protein Introduction

Introduction of ASIC4

ASIC4, also known as amiloride-sensitive cation channel 4 (ACCN4), is encoded by ASIC4 gene. It belongs to the ASIC/ENaC superfamily, and is predominantly distributed in mammalian nervous systems as well as non-neural tissues, such as cancer cells, articular chondrocytes, and intervertebral disc cells. Recent studies show ASIC4 plays crucial roles in modulating cell behavior via regulation of intracellular Ca²⁺ accumulation, including apoptosis, differentiation, and autophagy. Meanwhile, ASIC4 has been a novel pharmacological and therapeutic target for degenerative diseases.

Basic Information of ASIC4
Protein Name	Acid-sensing ion channel 4
Gene Name	ASIC4
Aliases	ACCN4
Organism	Homo sapiens (Human)
UniProt ID	Q96FT7
Transmembrane Times	2
Length (aa)	647
Sequence	MLSGAAGAARRGGAALAPSLTRSLAGTHAGADSCAGADKGSHKETIEERDKRQQRQQRQRQHQGCGAAGSGSDSPTSGPHPVPVLFPLALSLEEQPLPPLPLGRAPGLLAREGQGREALASPSSRGQMPIEIVCKIKFAEEDAKPKEKEAGDEQSLLGAVAPGAAPRDLATFASTSTLHGLGRACGPGPHGLRRTLWALALLTSLAAFLYQAAGLARGYLTRPHLVAMDPAAPAPVAGFPAVTLCNINRFRHSALSDADIFHLANLTGLPPKDRDGHRAAGLRYPEPDMVDILNRTGHQLADMLKSCNFSGHHCSASNFSVVYTRYGKCYTFNADPRSSLPSRAGGMGSGLEIMLDIQQEEYLPIWRETNETSFEAGIRVQIHSQEEPPYIHQLGFGVSPGFQTFVSCQEQRLTYLPQPWGNCRAESELREPELQGYSAYSVSACRLRCEKEAVLQRCHCRMVHMPDSLGGGPEGPCFCPTPCNLTRYGKEISMVRIPNRGSARYLARKYNRNETYIRENFLVLDVFFEALTSEAMEQRAAYGLSALLGDLGGQMGLFIGASILTLLEILDYIYEVSWDRLKRVWRRPKTPLRTSTGGISTLGLQELKEQSPCPSRGRVEGGGVSSLLPNHHHPHGPPGGLFEDFAC

Function of ASIC4 Membrane Protein

Acid-sensing ion channel 4 (ASIC4) has two hydrophobic transmembrane domains (TM1 and TM2), short intracellular N-and C- termini, and a large cysteine-rich extracellular loop. ASIC4 usually exists within inner ear neurons, adenohypophysis, and intervertebral disc. Multiple lines of evidence suggest that aberrant expression and activation of ASICs contribute to the progression of various degenerative diseases, including multiple sclerosis, Parkinson's disease, Huntington's disease, intervertebral disc degeneration and arthritis.

Fig.1 Closed (desensitized) rat ASIC4 model. (Sazanavets, 2015)

Application of ASIC4 Membrane Protein in Literature

Hoshikawa M., et al. Distribution of ASIC4 transcripts in the adult wild-type mouse brain. Neurosci Lett. 2017, 651: 57-64. PubMed ID: 28461138

This article analyzes the expression level of ASIC4 in the adult wild-type mouse brain. The result shows the ASIC4 mRNAs are widely expressed throughout the wild-type brain, but preferentially concentrate in several areas, which indicates ASIC4 may be related with some brain diseases.
Schwartz V., et al. Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression. Sci Rep. 2015, 5: 318242. PubMed ID: 26667795

Authors analyze the subcellular localization of ASIC4 in heterologous cell lines, which reveal a surprising accumulation of the channel in early endosome-related vacuoles. The data illustrate that heterologously expressed ASIC4 predominantly resides in an intracellular endosomal compartment.
Lin S.H., et al. Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety Function. Eur J Neurosci. 2015, 41(12): 1553-68. PubMed ID: 25828470

Authors in this group reveal that ASIC4 expression and physiological function on mice. The data suggest that ASIC4 might play an important role in modulating the innate fear response to predator odor and anxious state.

ASIC4 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ASIC4 antibody development services.

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Reference

Sazanavets I, et al. (2015). Computational Tools for Interpreting Ion Channel pH-Dependence. PLoS One. 10(4): e0125293.

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