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SLC4A2 Membrane Protein Introduction

Introduction of SLC4A2

SLC4A2, encoded by human SLC4A2 gene, also known as AE2, is a member of the SLC4 family of anion transporters which involves the bicarbonate transport across plasma membranes. The SLC4 polypeptides have several structural domains: two cytoplasmic domains, C- and N-terminal domains with 30-100 amino acids and 400-700 amino acids, respectively, and a C-terminal polytopic transmembrane domain with about 500 amino acids.

Basic Information of SLC4A2
Protein Name Anion exchange protein 2
Gene Name SLC4A2
Aliases AE2, HKB3, BND3L, NBND3, EPB3L1
Organism Homo sapiens (Human)
UniProt ID P04920
Transmembrane Times 10
Length (aa) 1241
Sequence MSSAPRRPAKGADSFCTPEPESLGPGTPGFPEQEEDELHRTLGVERFEEILQEAGSRGGEEPGRSYGEEDFEYHRQSSHHIHHPLSTHLPPDARRRKTPQGPGRKPRRRPGASPTGETPTIEEGEEDEDEASEAEGARALTQPSPVSTPSSVQFFLQEDDSADRKAERTSPSSPAPLPHQEATPRASKGAQAGTQVEEAEAEAVAVASGTAGGDDGGASGRPLPKAQPGHRSYNLQERRRIGSMTGAEQALLPRVPTDEIEAQTLATADLDLMKSHRFEDVPGVRRHLVRKNAKGSTQSGREGREPGPTPRARPRAPHKPHEVFVELNELLLDKNQEPQWRETARWIKFEEDVEEETERWGKPHVASLSFRSLLELRRTLAHGAVLLDLDQQTLPGVAHQVVEQMVISDQIKAEDRANVLRALLLKHSHPSDEKDFSFPRNISAGSLGSLLGHHHGQGAESDPHVTEPLMGGVPETRLEVERERELPPPAPPAGITRSKSKHELKLLEKIPENAEATVVLVGCVEFLSRPTMAFVRLREAVELDAVLEVPVPVRFLFLLLGPSSANMDYHEIGRSISTLMSDKQFHEAAYLADEREDLLTAINAFLDCSVVLPPSEVQGEELLRSVAHFQRQMLKKREEQGRLLPTGAGLEPKSAQDKALLQMVEAAGAAEDDPLRRTGRPFGGLIRDVRRRYPHYLSDFRDALDPQCLAAVIFIYFAALSPAITFGGLLGEKTQDLIGVSELIMSTALQGVVFCLLGAQPLLVIGFSGPLLVFEEAFFSFCSSNHLEYLVGRVWIGFWLVFLALLMVALEGSFLVRFVSRFTQEIFAFLISLIFIYETFYKLVKIFQEHPLHGCSASNSSEVDGGENMTWAGARPTLGPGNRSLAGQSGQGKPRGQPNTALLSLVLMAGTFFIAFFLRKFKNSRFFPGRIRRVIGDFGVPIAILIMVLVDYSIEDTYTQKLSVPSGFSVTAPEKRGWVINPLGEKSPFPVWMMVASLLPAILVFILIFMETQITTLIISKKERMLQKGSGFHLDLLLIVAMGGICALFGLPWLAAATVRSVTHANALTVMSKAVAPGDKPKIQEVKEQRVTGLLVALLVGLSIVIGDLLRQIPLAVLFGIFLYMGVTSLNGIQFYERLHLLLMPPKHHPDVTYVKKVRTLRMHLFTALQLLCLALLWAVMSTAASLAFPFILILTVPLRMVVLTRIFTDREMKCLDANEAEPVFDEREGVDEYNEMPMPV

Function of SLC4A2 Membrane Protein

SLC4A2 functions as Na+-independent electroneutral Cl--HCO3- exchanger that regulates electroneutral and reversible exchange of Cl- and HCO3- across the cell membrane. It is also involved in intracellular pH regulation and transepithelial acid-base transport. SLC4A2 has been shown to be expressed on the basolateral membranes of ileal and colonic epithelial cells in human where it is associated with vectorial chloride transport and maintenance of intracellular pH. Besides, SLC4A2 protein is also present in gastric parietal cells where it regulates acid secretion. The deficiency of SLC4A2 is involved in the pathogenesis of primary biliary cirrhosis (PBC). And mice with SLC4A2 knockdown have been shown as suitable animal models for studying PBC. The pathological study of PBC indicates that the decreased AE2 in lymphocytes may disorder pH regulation in these cells and change immune homeostasis resulting in autoimmunity, on the other hand, the reduced AE2 in cholangiocytes could lead to cholestasis and oxidative stress of bile duct cells.

Hepatobiliary transporters. Fig.1 Hepatobiliary transporters. (Joshi, 2010)

Application of SLC4A2 Membrane Protein in Literature

  1. Medina J.F. Role of the anion exchanger 2 in the pathogenesis and treatment of primary biliary cirrhosis. Digestive Diseases. 2011, 29(1):103-12. PubMed ID: 21691115

    The findings show that the bile duct cells isolated from PBC patients exhibit defective Na+-independent Cl-/HCO3- exchange, indicating the role of AE2 deficiency in the pathogenesis of PBC.

  2. Jeong Y.S. and Hong J.H. Governing effect of regulatory proteins for Cl(-)/HCO3(-) exchanger 2 activity. Channels. 2016, 10(3):214-224. PubMed ID: 26716707

    The results of the present study reveal the potential role of spinophilin (SPL) and carbonic anhydrase XII (CA XII) in mediating AE2 activity, suggesting these regulatory proteins may act as the therapeutic targets for secretory diseases mediated by AE2.

  3. Huang J., et al. Basolateral chloride loading by the anion exchanger type 2: role in fluid secretion by the human airway epithelial cell line Calu-3. Journal of Physiology. 2012, 590(21):5299-316. PubMed ID: 22802585

    In this research, the authors identify AE2 as a major pathway for basolateral Cl- loading during cAMP-stimulated secretion of Cl- and fluid by Calu-3 cells.

  4. Wang T., et al. EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells. Febs Journal. 2013, 280(1):174-183. PubMed ID: 23121767

    The article demonstrates a novel signal pathway involved in gastrin-stimulated AE2 expression mediated by EGR1 in gastric cancer cells.

  5. Vigliarolo T., et al. Abscisic acid influx into human nucleated cells occurs through the anion exchanger AE2. International Journal of Biochemistry & Cell Biology. 2016, 75:99-103. PubMed ID: 27015766

    Abscisic acid (ABA) is a hormone that regulates the responses to environmental stimuli, inflammatory responses, and glycemic concentrations. The research demonstrates ABA transport in human nucleated cells occurs via the anion exchanger AE2.

SLC4A2 Preparation Options

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Reference

  1. Joshi D, et al. (2010). Liver disease in pregnancy. Lancet. 375(9714): 594-605.

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