KIRREL1

NEPH1 is a member of the nephrin-like protein family, which includes NEPH2 (MIM 607761) and NEPH3 (MIM 607762). The cytoplasmic domains of these proteins interact with the C terminus of podocin (NPHS2; MIM 604766), and the genes are expressed in kidney podocytes, cells involved in ensuring size- and charge-selective ultrafiltration (Sellin et al., 2003 [PubMed 12424224]).

Full Name

Kirre Like Nephrin Family Adhesion Molecule 1

Function

Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm (PubMed:31472902).
It is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1 (By similarity).

Biological Process

Cell-cell adhesionManual Assertion Based On ExperimentIBA:GO_Central
Cell-cell junction maintenanceManual Assertion Based On ExperimentIMP:UniProtKB
ExcretionIEA:Ensembl
Glomerular filtrationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein phosphorylationIEA:Ensembl
Positive regulation of actin filament polymerizationIEA:Ensembl

Cellular Location

Cell membrane. Predominantly located at podocyte slit diaphragm.

Involvement in disease

Nephrotic syndrome 23 (NPHS23):
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 that progresses to end-stage renal failure. NPHS23 is an autosomal recessive form characterized by onset of proteinuria in the first or second decade of life, and variable outcome. Some patients have normal renal function after many years, whereas others may progress to chronic kidney disease.

Topology

Extracellular: 17-499
Helical: 500-520
Cytoplasmic: 521-757

PTM

Phosphorylation probably regulates the interaction with NSH2. Phosphorylated at Tyr-605 and Tyr-606 by FYN, leading to GRB2 binding (By similarity).
N-glycosylated.