Tight junctions mediate the regulation of the paracellular pathway between epithelial and endothelial cells. They form close connections to eliminate the extracellular space and regulate the flow of solutes between cells. The human gene PCLN-1 (paracellin-1) is related to the claudin family of integral membrane proteins, which localize to tight junctions. PCLN-1 contains four transmembrane domains and intracellular amino and carboxy termini, characteristic of the other claudin family members, and is detected only at the tight junctions of kidney tissue. PCLN-1 forms an intercellular pore and controls the resorption of magnesium and calcium in the thick ascending limb of Henle (TAL). Mutations in PCLN-1 cause renal magnesium wasting, which may contribute to a rare autosomal recessive disease, renal hypomagnesemia with hypercalciuria and nephrocalcinosis.
Function:
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in paracellular magnesium reabsorption. Required for a selective paracellular conductance. May form, alone or in partnership with other constituents, an intercellular pore permitting paracellular passage of magnesium and calcium ions down their electrochemical gradients. Alternatively, it could be a sensor of magnesium concentration that could alter paracellular permeability mediated by other factors.
Subcellular Location:
Cell junction; tight junction. Cell membrane.
Tissue Specificity:
Kidney-specific, including the thick ascending limb of Henle (TAL).
DISEASE:
Defects in CLDN16 are the cause of hypomagnesemia type 3 (HOMG3) [MIM:248250]; also known as familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). HOMG3 is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis. Recurrent urinary tract infections and kidney stones are often observed. In spite of hypercalciuria, patients do not show hypocalcemia.
Similarity:
Belongs to the claudin family.
SWISS:
Q9Y5I7
Gene ID:
10686
Database links:
Entrez Gene: 10686 Human
Entrez Gene: 114141 Mouse
Entrez Gene: 155268 Rat
Omim: 603959 Human
SwissProt: Q9Y5I7 Human
SwissProt: Q14BW2 Mouse
SwissProt: Q925N4 Mouse
SwissProt: Q91Y55 Rat
Unigene: 251391 Human
Unigene: 275205 Mouse
Unigene: 43852 Rat
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