+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin



Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin



Journal of the American Society of Nephrology 11(12): 2167-2178



Ankyrin-repeat family A protein (ANKRA) is a novel protein that interacts directly and specifically with the cytoplasmic tail of megalin in the yeast two-hybrid system and glutathione-S-transferase pull-down assays. ANKRA has three ankyrin repeats and shows 61% overall homology to regulatory factor X, ankyrin repeat-containing protein. Mapping studies show that the three ankyrin repeats and C-terminus of ANKRA are required for binding to a unique juxtamembrane, 19-amino acid sequence on the megalin tail. Point mutational analysis reveals that a proline-rich motif (PXXPXXP) within this region is the site of ANKRA binding. ANKRA interacts with megalin but not with low-density lipoprotein receptor related protein, in keeping with the fact that the sequence of the megalin tail is unique. By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. By immunofluorescence, ANKRA is concentrated near megalin along the plasma membrane of L2 cells and in the kidney cortex is expressed in glomerular and proximal tubule epithelia which also express megalin. These observations suggest that ANKRA may play a unique role in megalin's function as a clearance receptor in the kidney and L2 cells. In addition, ANKRA may have other partners because northern blot analysis reveals that ANKRA is more broadly expressed than megalin, and by immunofluorescence ANKRA is also expressed in connecting tubule cells and principal cells of collecting ducts.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 010301477

Download citation: RISBibTeXText

PMID: 11095640


Related references

Identification and functional characterization of ankyrin-repeat family protein ANKRA as a protein interacting with BKCa channel. Molecular Biology of the Cell 16(3): 1013-1025, 2004

Cloning and characterization of an ankyrin repeat protein that interacts with estrogen receptor and NF kappa B signaling pathways. Journal of Bone & Mineral Research 14(Suppl. 1): S453, 1999

Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners of class IIa histone deacetylases. Journal of Biological Chemistry 280(32): 29117-29127, 2005

SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function. Molecular and Cellular Biology 20(7): 2400-2410, 2000

The a-Helical D1 Domain of the Tobacco bZIP Transcription Factor BZI-1 Interacts with the Ankyrin-repeat Protein ANK1 and Is Important for BZI-1 Function, Both in Auxin Signaling and Pathogen Response. The Journal of Biological Chemistry 278(10): 86-94, 2003

The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1 interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1 function, both in auxin signaling and pathogen response. Journal of Biological Chemistry 278(10): 8786-8794, 2003

Characterization of proteins that physically interact with V-1, a cytoplasmic catecholamine biosynthesis-promoting ankyrin repeat protein. Japanese Journal of Pharmacology 82(Suppl 1): 56P, 2000

MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. Journal of Biological Chemistry 280(19): 19393-19400, 2005

Altered expression of cardiac ankyrin repeat protein and its homologue, ankyrin repeat protein with PEST and proline-rich region, in atrophic muscles in amyotrophic lateral sclerosis. Pathobiology 70(4): 197-203, 2003

Altered Expression of Cardiac Ankyrin Repeat Protein and Its Homologue, Ankyrin Repeat Protein with Pest and Proline-Rich Region, in Atrophic Muscles in Amyotrophic Lateral Sclerosis. Pathobiology 70(4): 197-203, 2002

The cell signaling adaptor protein EPS-8 is essential for C. elegans epidermal elongation and interacts with the ankyrin repeat protein VAB-19. Plos one 3(10): E3346, 2008

KB-Ras Binds to the Unique Insert within the Ankyrin Repeat Domain of IkcBb and Regulates Cytoplasmic Retention of IkBbNF-kB Complexes. The Journal of Biological Chemistry 278(25): 101-6, 2003

Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. Journal of Neuroscience 19(15): 6519-6527, 1999

Cloning and Characterization of Neuropilin-1-Interacting Protein: A Psd-95/Dlg/Zo-1 Domain-Containing Protein That Interacts with the Cytoplasmic Domain of Neuropilin-1. The Journal of Neuroscience 19(15): 6519-6527, 1999

A novel ankyrin-repeat protein interacts with the regulatory proteins of inner arm dynein f (I1) of Chlamydomonas reinhardtii. Cell Motility and the Cytoskeleton 66(8): 448-456, 2009