inversin (inversion of embryo turning homolog, nephrocystin-2, INVS, INV, NPHP2)

Function: 1) required for normal renal development & establishment of left-right axis 2) molecular switch between different Wnt signaling pathways (putative) 3) inhibits canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin- proteasome 4) required in renal development to oppose repression of terminal differentiation of tubular epithelial cells by Wnt signaling 5) binds calmodulin via its IQ domains 6) interacts with APC2 7) interacts with alpha-catenin, beta-catenin, gamma-catenin 8) interacts with N-cadherin (CDH2) 9) interacts with microtubules 10) interacts with NPHP1 11) interacts with DVL1, PRICKLE (PRICKLE1 or PRICKLE2) & Strabismus (VANGL1 or VANGL2) Structure: - contains 16 ANK repeats - contains 2 IQ domains - D-box 1 (destruction box 1) mediates interaction with APC2, may act as a recognition signal for degradation via ubiquitin-proteasome pathway Compartment: - cytoplasm, cytoskeleton, spindle, peripheral membrane, nucleus - associates with several components of cytoskeleton including ciliary, random & polarized microtubules - during mitosis, recruited to mitotic spindle - membrane localization is dependent upon cell-cell contacts & is redistributed when cell adhesion is disrupted Alternative splicing: named isoforms=3 Expression: - widely expressed - strongly expressed in primary cilia of renal tubular cells Pathology: - defects in INVS are the cause of nephronophthisis 2

Properties

SIZE: MW = 118 kD entity length = 1065 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: ankyrin repeat NAME: ankyrin repeat SITE: 13-42 ankyrin repeat NAME: ankyrin repeat SITE: 47-76 ankyrin repeat NAME: ankyrin repeat SITE: 80-110 ankyrin repeat NAME: ankyrin repeat SITE: 113-144 ankyrin repeat NAME: ankyrin repeat SITE: 148-177 ankyrin repeat NAME: ankyrin repeat SITE: 181-213 ankyrin repeat NAME: ankyrin repeat SITE: 220-250 ankyrin repeat NAME: ankyrin repeat SITE: 254-283 ankyrin repeat NAME: ankyrin repeat SITE: 288-317 ankyrin repeat NAME: ankyrin repeat SITE: 321-350 ankyrin repeat NAME: ankyrin repeat SITE: 356-385 ankyrin repeat NAME: ankyrin repeat SITE: 389-418 ankyrin repeat NAME: ankyrin repeat SITE: 422-451 ankyrin repeat NAME: ankyrin repeat SITE: 455-484 ankyrin repeat NAME: ankyrin repeat SITE: 488-517 MOTIF: ubiquitination site (destruction box, D-box) SITE: 490-498 FOR-BINDING-OF: ubiquitin ankyrin repeat NAME: ankyrin repeat SITE: 523-553 IQ motif {555-584} ubiquitination site (destruction box, D-box) SITE: 909-917 FOR-BINDING-OF: ubiquitin IQ motif {916-945}

Database Correlations

OMIM correlations MORBIDMAP 243305 UniProt Q9Y283 PFAM correlations

References

UniProt :accession Q9Y283