PDPN

This gene encodes a type-I integral membrane glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Podoplanin

Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:17616532, PubMed:18215137, PubMed:17222411).
Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN (PubMed:18541721).
Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness (PubMed:17046996, PubMed:21376833).
Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (PubMed:20962267).
In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (By similarity).
Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462).
In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:15515019).
Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (PubMed:25486435).
Required for normal lung cell proliferation and alveolus formation at birth (By similarity).
Does not function as a water channel or as a regulator of aquaporin-type water channels (PubMed:9651190).
Does not have any effect on folic acid or amino acid transport (By similarity).

Actin-mediated cell contractionISS:UniProtKB
Cell morphogenesisISS:UniProtKB
Cell-cell adhesionManual Assertion Based On ExperimentIBA:GO_Central
Lung developmentISS:UniProtKB
Lymph node developmentISS:UniProtKB
LymphangiogenesisISS:UniProtKB
Lymphatic endothelial cell fate commitmentISS:UniProtKB
Negative regulation of apoptotic processISS:UniProtKB
Negative regulation of cell population proliferationISS:UniProtKB
Platelet activationManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cellular component movementISS:UniProtKB
Positive regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of extracellular matrix disassemblyManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of platelet aggregationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cell shapeIEA:UniProtKB-KW
Regulation of lamellipodium morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of myofibroblast contractionISS:UniProtKB
Regulation of substrate adhesion-dependent cell spreadingISS:UniProtKB
Response to hyperoxiaManual Assertion Based On ExperimentIBA:GO_Central
Rho protein signal transductionManual Assertion Based On ExperimentIMP:UniProtKB
Wound healing, spreading of cellsManual Assertion Based On ExperimentIMP:UniProtKB

Podoplanin
Membrane
Cell projection, lamellipodium membrane
Cell projection, filopodium membrane
Cell projection, microvillus membrane
Cell projection, ruffle membrane
Membrane raft
Apical cell membrane
Basolateral cell membrane
Cell projection, invadopodium
Localized to actin-rich microvilli and plasma membrane projections such as filopodia, lamellipodia and ruffles (By similarity).
Association to the lipid rafts is required for PDPN-induced epithelial to mesenchymal transition (EMT) (PubMed:21376833).
Colocalizes with CD9 in tetraspanin microdomains (PubMed:18541721).
Localized at invadopodium adhesion rings in tumor cell. Association to the lipid rafts is essential for PDPN recruitment to invadopodia and ECM degradation (PubMed:25486435).
29kDa cytosolic podoplanin intracellular domain
Cytoplasm, cytosol

Extracellular: 23-131
Helical: 132-152
Cytoplasmic: 153-162

Extensively O-glycosylated. Contains sialic acid residues. O-glycosylation is necessary for platelet aggregation activity. Disialylated at Thr-52; sialic acid is critical for platelet-aggregating activity and for CLEC1B interaction (PubMed:17222411, PubMed:25458834).
The N-terminus is blocked.
Cleaved by a metalloprotease within its extracellular (EC) domain, generating a membrane-bound C-terminal fragment (PCTF33) and an extracellular fragment. The resulting membrane-bound C-terminal fragment (PCTF33) is further processed between Val-150 and Val-151 by PSEN1/gamma-secretase generating the intracellular domain of podoplanin (PICD).