Sodium-hydrogen exchange regulatory cofactor 2
Encyclopedia
Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF-2) also known as tyrosine kinase activator protein 1 (TKA-1) or SRY-interacting protein 1 (SIP-1) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the SLC9A3R2 (solute carrier family 9 isoform A3 regulatory factor 2) gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

NHERF-2) is a scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin
Merlin (protein)
Merlin is a cytoskeletal protein. In humans, it is a tumor suppressor protein involved in Neurofibromatosis type II. Sequence data reveal its similarity to the ERM protein family....

 family and thereby helps to link them to the actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

 and to regulate their surface expression. It is necessary for cAMP-mediated phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 and inhibition of SLC9A3. In addition, it may also act as scaffold protein in the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

.

Function

This regulatory protein (factor) interacts with a sodium/hydrogen exchanger NHE3 (SLC9A3) in the brush border membrane of the proximal tubule
Proximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...

, small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

, and colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

 that plays a major role in transepithelial sodium absorption. SLC9A3R2, as well as SLC9A3R1 and protein kinase A phosphorylation, may play a role in NHE3 regulation.

Interactions

Sodium-hydrogen exchange regulatory cofactor 2 has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with SGK
SGK
Serine/threonine-protein kinase SGK is a kinase subfamily that is currently known as being encoded by SGK1, SGK2, and SGK3 genes.The SGK1 kinase regulates the myo-inositol transporter during osmotic stress....

, Actinin alpha 4
Actinin alpha 4
Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.-Interactions:Actinin alpha 4 has been shown to interact with PDLIM1, Sodium-hydrogen exchange regulatory cofactor 2, Collagen, type XVII, alpha 1, CAMK2A, CAMK2B, MAGI1 and TRIM3.-Further reading:...

, Parathyroid hormone receptor 1
Parathyroid hormone receptor 1
Parathyroid hormone/parathyroid hormone-related peptide receptor also known as parathyroid hormone 1 receptor is a protein that in humans is encoded by the PTH1R gene...

, Phosphoinositide-dependent kinase-1
Phosphoinositide-dependent kinase-1
In the field of biochemistry, 3-phosphoinositide dependent protein kinase-1, also known as PDPK1 is a protein which in humans is encoded by the PDPK1 gene.PDPK1 is also known as "PDK1"...

, EZR, PODXL
PODXL
Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene.-Interactions:PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.-Further reading:...

, Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...

 and PLCB3
PLCB3
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene. The gene codes for the enzyme phospholipase C β3. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...

.

Further reading

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