podocalyxin; GCTM-2 antigen; Gp200; podocalyxin-like protein 1; PC; PCLP-1 (PODXL, PCLP, PCLP1)

Function: - antiadhesin that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion - acts as a pro-adhesive molecule, enhancing adherence of cells to immobilized ligands, increasing the rate of migration & cell-cell contacts (integrin-dependent) - induces formation of apical actin-dependent microvilli - role in formation of a preapical plasma membrane subdomain to set up initial epithelial polarization & the apical lumen formation during renal tubulogenesis - monomer; when associated with the membrane raft - oligomer; when integrated in the apical membrane - interacts (via C-terminal PDZ-binding motif DTHL) with SLC9A3R1 (via PDZ domains); the interaction - is not detected in glomerular epithelial cells - takes place early in the secretory pathway - is necessary for its apical membrane sorting - found in a complex with EZR, PODXL & SLC9A3R2 - associates with the actin cytoskeleton through complex formation with EZR & SLC9A3R2 - interacts (via C-terminal PDZ-binding motif DTHL) with SLC9A3R2 (via PDZ domain 1) - interaction is detected in glomerular epithelial cells (putative) - interacts with EZR Structure: - N- & O-linked glycosylated - sialoglycoprotein - both the O-glycan-rich domain of the extracellular domain & the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal - cytoplasmic domain is necessary for the apical membrane targeting & renal tubulogenesis - cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with SLC9A3R1 & for targeting SLC9A3R1 to the apical cell membrane - extracellular domain is necessary for microvillus formation (putative) - large highly anionic extracellular domain facilitates open filtration pathways between neighboring podocyte foot processes - belongs to the podocalyxin family Compartment: - apical cell membrane - cell projection, lamellipodium, filopodium, ruffle, microvillus (putative) - membrane raft (putative) - single-pass type 1 membrane protein (putative) - in single attached epithelial cells is restricted to a preapical pole on the free plasma membrane whereas other apical & basolateral proteins are not yet polarized - colocalizes with SLC9A3R2 at the apical plasma membrane during epithelial polarization - colocalizes with SLC9A3R1 at the trans-Golgi network (transiently) & at the apical plasma membrane - its association with the membrane raft is transient - colocalizes with actin filaments, EZR & SLC9A3R1 in a punctate pattern at the apical cell surface where microvilli form - colocalizes with EZR & SLC9A3R2 at the apical cell membrane of glomerular epithelium cells (putative) - forms granular, punctuated pattern, forming patches, preferentially adopting a polar distribution, located on the migrating poles of the cell or forming clusters along the terminal ends of filipodia establishing contact with the endothelial cells - colocalizes with the submembrane actin of lamellipodia, particularly associated with ruffles - colocalizes with vinculin at protrusions of cells - colocalizes with ITGB1 Alternative splicing: named isoforms=2 Expression: - expressed in glomerular epithelium cell (podocyte) Pathology: - role in regulation of both adhesion & cell morphology & cancer progression - plays a role in cancer development & aggressiveness by inducing cell migration & invasion through its interaction with the actin-binding protein EZR - affects EZR-dependent signaling events, leading to increased activities of the MAPK & PI3K pathways in cancer cells

General

membrane protein sialoglycoprotein

Properties

SIZE: entity length = 558 aa MW = 59 kD COMPARTMENT: plasma membrane golgi MOTIF: signal sequence {1-22} N-glycosylation site {N33} threonine-rich region {35-334} MOTIF: threonine residue (SEVERAL) N-glycosylation site {N43} N-glycosylation site {N104} N-glycosylation site {N144} N-glycosylation site {N360} transmembrane domain {462-482}

Database Correlations

OMIM 602632 UniProt O00592 Pfam PF06365 Entrez Gene 5420 Kegg hsa:5420

References

UniProt :accession O00592