Juvenile nephronophthisis type 1 is caused by mutations of NPHP1, the gene encoding for nephrocystin. Nephrocystin interacts with p130Cas (BCAR1), proline-rich tyrosine kinase-2 (PTK2B or Pyk2), and tensin in embryonic kidney and testis, indicating that these proteins participate in a common signaling pathway. Nephrocystin and p130Cas interact in mammalian cells and both proteins prominently localize at or near sites of cell-cell contact in polarized Madin-Darby canine kidney epithelial cells. Expression of nephrocystin results in phosphorylation of Pyk2 on Tyrosine 402 as well as activation of downstream mitogen-activated protein kinases, such as ERK1 and ERK2. Nephrocystin contains a src-homology 3 (SH3) domain, which is highly conserved throughout evolution.
Juvenile nephronophthisis 1 protein; nephrocystin 1; Nephrocystin-1; nephronophthisis 1 (juvenile); nephronophthisis 1 (juvenile) homolog