Na+/H+ exchange regulatory cofactor NHE-RF1; NHERF-1; Ezrin-radixin-moesin-binding phosphoprotein 50; EBP50; regulatory cofactor of Na+/H+ exchanger; Na+-hydrogen exchanger regulatory factor 1; solute carrier family 9 isoform A3 regulatory factor 1 (SLC9A3R1, NHERF, NHERF1)

Function: - scaffold protein - connects plasma membrane proteins with members of the ezrin/moesin/radixin family & thereby helps to link them to the actin cytoskeleton & to regulate their surface expression - necessary for recycling of internalized ADRB2 - first known to play a role in the regulation of the activity & subcellular location of SLC9A3 - necessary for cAMP-mediated phosphorylation & inhibition of SLC9A3. - may enhance Wnt signaling - may participate in HTR4 targeting to microvilli - interacts with MCC - phosphorylated on Ser - homodimer, & heterodimer with SLC9A3R2 - binds the N-termini of EZR, RDX & MSN. binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2 & CFTR. binds ARHGAP17, EPI64, GNB2L1, OPRK1, GNAQ, CTNNB1 & PLCB3 - binds PDZK1 (putative) - interacts with CLCN3 - binds the C-terminus of PAG1 - in resting T- cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation - forms a complex with CFTR & SLC4A7 - forms a complex with SLC4A7 & ATP6V1B1 - interacts with TRPC4 (via the PDZ-binding domain) - directly interacts with HTR4 (putative) - interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is not detected in glomerular epithelium cells - interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); the interaction occurs early in the secretory pathway & is necessary for its apical membrane sorting (putative) Structure: contains 2 PDZ domain (DHR domain)s Compartment: - cytoplasm (putative) - apical cell membrane (putative) - endomembrane system; peripheral membrane protein - cell projection, filopodium, ruffle, microvillus - translocates from the cytoplasm to the apical cell membrane (PODXL-dependent) - colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast - found in microvilli, ruffling membrane & filopodia of HeLa cells - present in lipid rafts of T-cells Expression: - detected in liver, kidney, pancreas, prostate, spleen, small intestine & placenta, in particular in the syncytiotrophoblast - induced by estrogen Pathology: - defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2

General

phosphoprotein scaffold protein

Properties

SIZE: entity length = 358 aa MW = 39 kD COMPARTMENT: cytoplasm MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl PDZ domain NAME: PDZ domain SITE: 14-94 MOTIF: Ser phosphorylation site {S46} PDZ domain NAME: PDZ domain SITE: 154-234 Ser phosphorylation site {S280} Ser phosphorylation site {S288} Ser phosphorylation site {S290} Ser phosphorylation site {S291} Thr phosphorylation site {T293} Ser phosphorylation site {S294} Ser phosphorylation site {S302}

Database Correlations

OMIM correlations MORBIDMAP 604990 UniProt O14745 PFAM correlations Entrez Gene 9368 Kegg hsa:9368

References

UniProt :accession O14745