FXYD4 Membrane Protein Introduction

Introduction of FXYD4

FXYD4 is encoded by the FXYD4 gene which is located at 10q11.21. The molecular weight of FXYD4 is about 9 KDa. It belongs to the FXYD family which are named after an invariant PFXYD amino acid motif in their extracellular domain. The FXYD motif of FXYD4 is crucial for its biological function. What’ s more, FXYD4 is a single-pass type I membrane protein which spans the membrane once, with its N-terminus on the extracellular side of the membrane and removal of its signal sequence.

Basic Information of FXYD4
Protein Name	FXYD domain-containing ion transport regulator 4
Gene Name	FXYD4
Aliases	NA
Organism	Homo sapiens (Human)
UniProt ID	P59646
Transmembrane Times	Single-pass membrane
Length (aa)	89
Sequence	MERVTLALLLLAGLTALEANDPFANKDDPFYYDWKNLQLSGLICGGLLAIAGIAAVLSGKCKCKSSQKQHSPVPEKAIPLITPGSATTC

Function of FXYD4 Membrane Protein

FXYD4 is a tissue-special regulator of N, K-ATPase (NKA) which is associated with NKA in the renal tissue and modulates the N, K-pump transport. Besides, FXYD4 can interact selectively and non-covalently with an ATPase. It also contains potassium channel activity and sodium channel regulator activity. In fact, FXYD protein is wildly distributed in human tissues. For FXYD4, it is prominently expressed in the distal colon and the medullary collecting duct of the kidney. It is important that the interaction between FXYD4 and NKA will affect the apparent affinity for extracellular Na⁺. The Na⁺ affinity of Na, K-ATPase increases in renal segment because of the association with FXYD4 which permits efficient Na⁺ reabsorption even at low intracellular Na⁺ concentrations. So, FXYD4 is predicted to play a crucial role in aldosterone-responsive tissues responsible for maintaining the body Na⁺ and K⁺ homeostasis. It is worth mentioning that FXYD4 has the opposite effect on the afﬁnity for intra-cellular Na⁺ of Na, K-ATPase.

FXYD4 Membrane Protein Introduction Fig.1 Structural and functional interaction sites between Na, K-ATPase and FXYD proteins (Geering, 2005).

Application of FXYD4 Membrane Protein in Literature

Geering K., Function of FXYD Proteins, Regulators of Na, K-ATPase. Journal of Bioenergetics & Biomembranes. 2005, 37(6):387-392. PubMed ID: 16691470

Authors discuss the role of FXYD proteins as tissue-speciﬁc modulators of Na, K-ATPase. FXYD4 associates with Na, K-ATPase α1-β complexes both after coexpression in oocytes and in the kidney. FXYD4 affects the apparent afﬁnity for extracellular Na⁺, it is related to the homeostasis of Na⁺.
Pestov N.B., et al. Postnatal regulation of X, K-ATPases in rat skin and conserved lateroapical polarization of Na, K-ATPase in vertebrate epidermis. Experimental Dermatology. 2013, 22(6):423-425. PubMed ID: 23651441

Authors in this article focus on ion-transporting enzymes involved in the development of epidermis. They characterize the expression of Na, K- and H, K-ATPase α and β subunits and FXYD isoforms in rat skin. They find that maturation of rat skin from newborn to adult is associated with an increase in FXYD4.
Béguin P., et al. CHIF, a member of the FXYD protein family, is a regulator of Na, K-ATPase distinct from the γ-subunit. Embo Journal. 2001, 20(15):3993-4002. PubMed ID: 11483503

This article suggests that FXYD4 is a regulator of Na, K-ATPase (NKA), and it also reveals that FXYD4 is type I membrane protein and it associates with NKA in renal tissue. Beyond that, FXYD4 may play a crucial role in aldosterone-responsive tissues responsible for maintaining the body Na⁺ and K⁺ homeostasis.
Garty H., et al. A Specific Functional Interaction between CHIF and Na,K‐ATPase. American Journal of Physiology Renal Physiology. 2002, 283(4): F607. PubMed ID: 12217851

This article reveals that mutually exclusive expression of FXYD4 and gamma in different nephron segments. It is important that FXYD4 induces a two- to threefold increase in apparent affinity for cytoplasmic Na (K'(Na)) but does not affect affinity for extracellular K (Rb) ions (K'(K)) or V(max).

FXYD4 Preparation Options

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Reference

Geering K. (2005). Function of FXYD proteins, regulators of Na, K-ATPase. Journal of Bioenergetics & Biomembranes, 37(6), 387-392.

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