The FXYD protein family is a family of small
membrane protein
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...
s that share a 35-amino acid signature sequence domain, beginning with the
amino acid sequence
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...
PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator.
It contains at least seven members in mammals.
Two other family members that are not obvious
ortholog
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...
s of any identified mammalian FXYD protein exist in zebrafish. All these proteins share a signature sequence of six conserved amino acids comprising the FXYD motif in the NH2-terminus, and two
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
s and
one
serine
Serine
(symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
residue in the
transmembrane domain
A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...
. FXYD proteins are widely distributed in mammalian tissues with prominent expression in tissues that perform fluid and solute transport or that are electrically excitable.
Initial functional characterization suggested that FXYD proteins act as channels or as modulators of
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s. However, studies have revealed that most FXYD proteins have another specific function and act as tissue-specific
regulatory subunits of the
Na,K-ATPase. Each of these auxiliary subunits produces a distinct functional effect on the transport characteristics of the Na,K-ATPase that is adjusted to the specific functional demands of the tissue in which the FXYD protein is expressed. FXYD proteins appear to preferentially associate with Na,K-ATPase alpha1-beta
isozyme
In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. di ...
s, and affect their function in a way that render them operationally complementary or supplementary to coexisting isozymes.
Human proteins containing this domain
FXYD1;
FXYD2;
FXYD3;
FXYD4;
FXYD5;
FXYD6;
FXYD7;
FXYD8;
KCT1;
References
{{InterPro content, IPR000272
Protein domains
Protein families
Single-pass transmembrane proteins