ASIC2 Membrane Protein Introduction

Introduction of ASIC2

ASIC2, also known as amiloride-sensitive cation channel 1, neuronal (ACCN1) or brain sodium channel 1 (BNaC1), is encoded by ASIC2 gene. It belongs to the ASIC/ENaC superfamily, and is widely distributed within mammalian nervous systems as well as non-neural tissues, such as cancer cells, articular chondrocytes and intervertebral disc cells, where it plays significant pathophysiological roles.

Basic Information of ASIC2
Protein Name	Acid-sensing ion channel 2
Gene Name	ASIC2
Aliases	ACCN, ACCN1, BNAC1, MDEG
Organism	Homo sapiens (Human)
UniProt ID	Q16515
Transmembrane Times	2
Length (aa)	512
Sequence	MDLKESPSEGSLQPSSIQIFANTSTLHGIRHIFVYGPLTIRRVLWAVAFVGSLGLLLVESSERVSYYFSYQHVTKVDEVVAQSLVFPAVTLCNLNGFRFSRLTTNDLYHAGELLALLDVNLQIHLPDPADPSVLEALRQKANFKHYKPKQFSMLEFLHRVGHDLKDMMLYCKFKGQECGHQDFTTVFTKYGKCYMFNSGEDGKPLLTTVKGGTGNGLEIMLDIQQDEYLPIWGETEETTFEAGVKVQIHSQSEPPFIQELGFGVAPGFQTFVATQEQRLTYLPPPWGECRSSEMGLDFFPVYSITACRIDCETRYIVENCNCRMVHMPGDAPFCTPEQHKECAEPALGLLAEKDSNYCLCRTPCNLTRYNKELSMVKIPSKTSAKYLEKKFNKSEKYISENILVLDIFFEALNYETIEQKKAYEVAALLGDIGGQMGLFIGASILTILELFDYIYELIKEKLLDLLGKEEDEGSHDENVSTCDTMPNHSETISHTVNVPLQTTLGTLEEIAC

Function of ASIC2 Membrane Protein

Acid-sensing ion channel 2 (ASIC2) has two hydrophobic transmembrane domains (TM1 and TM2), short intracellular N-and C- termini, and a large cysteine-rich extracellular loop. ASIC2a and ASIC2b subunits are primarily localized in the central nervous system (CNS). Previous studies suggest that ASIC2a shows low sensitivity to reduced extracellular pH (pH50=4.35) and slow channel inactivation. Moreover, ASIC2b does not form functional ion channels by itself. Recent studies show ASIC2 is related with various diseases, such as, Parkinson's disease, Intervertebral Disc Degeneration as well as Arthritis.

Fig.1 The structure and electrophysiological properties of ASICs. (Zhou, 2015)

Application of ASIC2 Membrane Protein in Literature

Zhou Z.H., et al. The acid-sensing ion channel, ASIC2, promotes invasion and metastasis of colorectal cancer under acidosis by activating the calcineurin/NFAT1 axis. J Exp Clin Cancer Res. 2017, 36(1): 130. PubMed ID: 28927426

This article analyzes the expression level of ASIC2 and identifies the function of ASIC2 on colorectal cancer. The results suggest that ASIC2 can highly express in patients with CRC and activate the calcineurin/NFAT1 pathway to promote CRC cells metastasis.
Zhang S., et al. The Novel ASIC2 Locus is Associated with Severe Gingival Inflammation. JDR Clin Trans Res. 2016, 1(2): 163-170. PubMed ID: 28459102

Authors conduct a genome-wide association study of severe GI among 4077 European American adults to find the association between ASIC2 with severe gingival inflammation (GI). The data show that the genetic variation in ASIC2 is significantly associated with severe gingival inflammation and the association is plaque-independent.
Kweon H.J., et al. Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly. Sci Rep. 2016, 6: 30684. PubMed ID: 27477936

Authors in this group reveal the underlying mechanism of ASIC2 differential subcellular distribution. The data suggest ASIC2a plays an important role in membrane targeting of ASIC2b.
Jiang N., et al. Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury. J Cereb Blood Flow Metab. 2017, 37(2): 528-540. PubMed ID: 626861816

This article analyses the association between ASIC2 and ASIC1 expressions in an ASIC2 deletion C57BL/6 mice model. The data demonstrated that ASIC2 deletion plays an important role in acid-activated current in various brain regions, which should be related with acidosis/ischemia-induced neuronal injury.
Cuesta A., et al. Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc. Int J Clin Exp Pathol. 2015, 8(9): 10305-14. PubMed ID: 26617738

Authors in this group examine the expression of ASIC2 in human normal and the intervertebral disc (IVD) in TrkB-deficient mice using a variety of methods, such as quantitative-PCR and Western blot. The results suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression.

ASIC2 Preparation Options

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Reference

Zhou R P, et al. (2015). Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases. Aging Dis. 7(4): 491-501.

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