FXYD3 Membrane Protein Introduction

Introduction of FXYD3

FXYD3 is encoded by the FXYD3 gene which is located at 19q13.1. The molecular mass of FXYD3 is about 15 KDa. It belongs to the FXYD family which is a family of small membrane proteins, with a common 35-amino acid signature sequence domain that begins with the amino acid sequence PFXYD. In addition, FXYD3 is a single-pass type I membrane protein with its N-terminus on the extracellular side of the membrane and removal of its signal sequence. Different from other FXYD, FXYD3 contains a noncleavable signal peptide which makes it possible to have a second transmembrane-like domain.

Function of FXYD3 Membrane Protein

FXYD3 is also known as the gamma subunit of the Na, K-ATPase (NKA). It can associate with and modify the transport properties of Na, K-ATPase. FXYD1 will take part in chloride transport, potassium ion transport, regulation of sodium ion transmembrane transporter activity and some other biological processes. Especially, when expressed in Xenopus oocytes, FXYD3 can interact with Na, K- as well as H, K-ATPases and influence their glycosylation processing. FXYD3 is able to influence glycosylation processing of the β-subunits of NKA, reversing glutathionylation-mediated inhibition of ATP1B1. Beyond that, the clinical significance of FXYD3 has been demonstrated in a few types of cancer, such as endometrial cancer, rectal cancer. In human hepatocellular carcinoma (HCC), the expression level of FXYD3 is significantly increased at the mRNA and protein levels in HCC tumor tissues compared with adjacent non‑cancerous tissues. FXYD3 protein may act as a prognostic marker for HCC.

Fig.1 TAZ-FXYD-3 complex, FXYD3 is represented in cyan (Pathak, 2014).

Application of FXYD3 Membrane Protein in Literature

1. Wang L.J., et al. Prognostic significance of sodium-potassium ATPase regulator, FXYD3, in human hepatocellular carcinoma. Oncology Letters. 2018, 15(3):3024-3030. PubMed ID: 29435033
   
   

   Authors in this article investigate the role of FXYD3 in human hepatocellular carcinoma (HCC). They find a significant increase of FXYD3 at the mRNA and protein levels in HCC tumor tissues compared with adjacent non-cancerous tissues. Thus, they think that FXYD3 protein may serve as a prognostic marker for HCC.

2. Loftas P., et al. FXYD-3 expression in relation to local recurrence of rectal cancer. Radiation Oncology Journal. 2016, 34(1):52-58. PubMed ID: 27104167
   
   

   To confirm a previous study in which FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer, authors of this article investigate the expression and some other important values. They conclude that it is unable to confirm the previous result in a cohort of rectal cancer patients who developed local recurrence.

3. Staff P.O. Correction: Gluco-Incretins Regulate Beta-Cell Glucose Competence by Epigenetic Silencing of Fxyd3 Expression. Plos One. 2014, 9(7): e103277-e103277. PubMed ID: 25058609
   
   

   This article reveals that the epigenetic regulation of FXYD3 expression may link nutrition in early life to establishment of adult beta-cell glucose competence. However, the regulation is lost in diabetes possibly because of gluco-incretin resistance and/or de-differentiation of beta-cells.

4. Liu C.C., et al. Silencing overexpression of FXYD3 protein in breast cancer cells amplifies effects of doxorubicin and γ-radiation on Na (+)/K (+)-ATPase and cell survival. Breast Cancer Research & Treatment. 2016, 155(2):203-213. PubMed ID: 26740212
   
   

   Authors in this article aim to investigate if the overexpression of FXYD3 in several cancers might protect Na (+)/K (+)-ATPase and cancer cells against the high levels of oxidative stress characteristic of many tumors and often induced by cancer treatments. They find that FXYD3 may be a marker of resistance to cancer treatments and a potentially important therapeutic target.

5. Pathak S., et al. Tafazzin Protein Expression Is Associated with Tumorigenesis and Radiation Response in Rectal Cancer: A Study of Swedish Clinical Trial on Preoperative Radiotherapy. Plos One. 2014, 9(5): e98317. PubMed ID: 24858921
   
   

   This article aims at Tafazzin (TAZ), a transmembrane protein whose mutations is associated with several diseases. In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30, and FXYD-3.

FXYD3 Preparation Options

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Reference

1. Pathak S., et al. (2014). Tafazzin protein expression is associated with tumorigenesis and radiation response in rectal cancer: a study of swedish clinical trial on preoperative radiotherapy. Plos One. 9(5), e98317.

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