INVS
Domain
The D-box 1 (destruction box 1) mediates the interaction with APC2, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway.
Function
Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity).
Involvement in disease
Nephronophthisis 2
NPHP2
An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo-interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
May be ubiquitinated via its interaction with APC2.
Hydroxylated at Asn-75, most probably by HIF1AN.
Tissue Specificity
Widely expressed. Strongly expressed in the primary cilia of renal tubular cells.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cytoskeleton
- Spindle
- Membrane
- Peripheral membrane protein
- Nucleus
- Cell projection
- Cilium
- Associates with several components of the cytoskeleton including ciliary, random and polarized microtubules. During mitosis, it is recruited to mitotic spindle. Frequently membrane-associated, membrane localization is dependent upon cell-cell contacts and is redistributed when cell adhesion is disrupted after incubation of the cell monolayer with low-calcium/EGTA medium.
Alternative names
INV, NPHP2, INVS, Inversin, Inversion of embryo turning homolog, Nephrocystin-2