Nephrocystin proteins and their protein domains. Domain structure of the nephrocystin proteins. Nephrocystin proteins contain a diverse variety of protein domains and no common pattern can be identified. Nephrocystin-1, encoded by NPHP1, is a 732 amino acid (aa) protein, which possesses an N-terminal coiled-coil domain (CC) and a Src-homology 3 domain (SH3). Nephrocystin-2 (alias inversin), encoded by NPHP2/INVS, is a 1260 aa protein with 16 tandem ankyrin repeats, two IQ calmodulin binding domains (IQ). There are two destruction-box (D-box) regions (the first of which is Apc2 binding) and a bipartite nuclear localization signal (b-NLS) and a putative coiled-coil (CC) domain. Nephrocystin-3, encoded by NPHP3, is a 1330 aa protein, with a coiled-coil domain (CC), a tetratricopeptide-repeat domain (TPR) and a tubulin tyrosine ligase domain (TTL). Within the TTL a STAND (signal transduction ATPases with numerous domains) domain, which may be found in P-loop NTPases, is located. Nephrocystin-4 (alias nephroretinin), encoded by NPHP4 is a 1426 aa protein, which lacks any known domains. There is a central proline rich region. Nephrocystin-5, encoded by NPHP5/IQCB1 is a 598 aa protein. This protein possesses two IQ calmodulin binding sites, which surround a putative coiled-coil (CC) domain. Nephrocystin-6 (alias CEP290) is encoded by NPHP6/CEP290. This is a 2479 aa protein with multiple domains which include 13 coiled-coil (CC) domains; 3 tropomyosin homology domains (TM); 6 RepA/Rep+ protein KID motifs (KID); a bipartite nuclear localization signal (b-NLS); a ATP/GTP-binding site motif A (p-loop). The extent of homology with Structural Maintenance of Chromosomes proteins (SMC) is also indicated. AHI1 (alias Jouberin) is encoded by AHI1 and is an 1196 aa protein, which contains a Src-homology 3 domain (SH3), 6 WD40 domains (WD40) and an N-terminal coiled-coil domain. GLIS family zinc finger 2 (alias nephrocystin-7) is a 524 aa protein encoded by GLIS2. It contains 5 zinc finger domains (ZnF). RPGRIP1L (alias nephrocystin-8) is a 1315 aa protein encoded by RPGRIP1L. Protein domains include 6 coiled-coil (CC) domains and two protein kinase C conserved region 2 (C2) domains. The C-terminal C2 domain mediates the interaction with nephrocystin-4. NEK8 (alias nephrocystin-9) is a 692 aa protein with a serine/threonine protein kinases, catalytic domain (S-TKc) and a regulator of chromosome condensation (RCC1) domain, which is highly conserved throughout evolution.