Recombinant Human Nephrin (NPHS1), partial

Function

Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion (By similarity)

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Disease Association

Nephrotic syndrome 1 (NPHS1) : A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Specifically expressed in podocytes of kidney glomeruli

Subunit

Self-associates (via the Ig-like domains) (By similarity). Interacts with CD2AP (via C-terminal domain) (By similarity). Interacts with NPHS2 (PubMed:11562357). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex with IGSF5/JAM4 (By similarity). Interacts with DDN; the interaction is direct (By similarity). Also interacts (via the Ig-like domains) with KIRREL1/NEPH1 and KIRREL2; the interaction with KIRREL1 is dependent on KIRREL1 glycosylation (By similarity). Interacts with KIRREL3 (By similarity). Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 (By similarity). Interacts with phosphatidylinositol 3-kinase regulatory subunit PIK3R1; the interaction is reduced by high glucose levels (PubMed:28955049). Interacts (via N-terminus) with GAPVD1 (via Ras-GAP or VPS9 domains) (PubMed:29959197)

• Kestilae M. et al. Positionally cloned gene for a novel glomerular protein -- nephrin -- is mutated in congenital nephrotic syndrome. — Mol. Cell (1998)
• Tikhomirov E. et al. Novel human pathological mutations. Gene symbol: NPHS1. Disease: congenital nephrotic syndrome, Finnish type. — Hum. Genet. (2009)
• Grunkemeyer J.A. et al. Human nephrin (NPHS1) cDNA sequence. (SEP-)
• Grimwood J. et al. The DNA sequence and biology of human chromosome 19. — Nature (2004)
• Holthoefer H. et al. Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney. — Am. J. Pathol. (1999)
• Ruotsalainen V. et al. Nephrin is specifically located at the slit diaphragm of glomerular podocytes. — Proc. Natl. Acad. Sci. U.S.A. (1999)
• Huber T.B. et al. Interaction with podocin facilitates nephrin signaling. — J. Biol. Chem. (2001)
• Zahedi R.P. et al. Phosphoproteome of resting human platelets. — J. Proteome Res. (2008)