3iet

Structural highlights

Function

PDPN_MOUSE 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:20110424, PubMed:17616532). Interaction with CD9, on the contrary, attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Mediates effects on cell migration and adhesion through its different partners. 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. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (By similarity). 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 (PubMed:25347465). Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (By similarity). 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:10574709). 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 (By similarity). Required for normal lung cell proliferation and alveolus formation at birth (PubMed:12654292). Does not function as a water channel or as a regulator of aquaporin-type water channels (By similarity). Does not have any effect on folic acid or amino acid transport (PubMed:12032185).[UniProtKB:Q86YL7]^{[1] [2] [3] [4] [5] [6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Scholl FG, Gamallo C, Vilaró S, Quintanilla M. Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci. 1999 Dec;112 ( Pt 24):4601-13. PMID:10574709 doi:10.1242/jcs.112.24.4601
2. ↑ Boucherot A, Schreiber R, Pavenstädt H, Kunzelmann K. Cloning and expression of the mouse glomerular podoplanin homologue gp38P. Nephrol Dial Transplant. 2002 Jun;17(6):978-84. PMID:12032185 doi:10.1093/ndt/17.6.978
3. ↑ Ramirez MI, Millien G, Hinds A, Cao Y, Seldin DC, Williams MC. T1alpha, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Dev Biol. 2003 Apr 1;256(1):61-72. PMID:12654292 doi:10.1016/s0012-1606(02)00098-2
4. ↑ Kato Y, Fujita N, Kunita A, Sato S, Kaneko M, Osawa M, Tsuruo T. Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. J Biol Chem. 2003 Dec 19;278(51):51599-605. PMID:14522983 doi:10.1074/jbc.M309935200
5. ↑ Kaneko M, Kato Y, Kunita A, Fujita N, Tsuruo T, Osawa M. Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. J Biol Chem. 2004 Sep 10;279(37):38838-43. PMID:15231832 doi:10.1074/jbc.M407210200
6. ↑ Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, Yamazaki Y, Narimatsu H, Ozaki Y. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem. 2007 Sep 7;282(36):25993-6001. PMID:17616532 doi:10.1074/jbc.M702327200
7. ↑ Uhrin P, Zaujec J, Breuss JM, Olcaydu D, Chrenek P, Stockinger H, Fuertbauer E, Moser M, Haiko P, Fässler R, Alitalo K, Binder BR, Kerjaschki D. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood. 2010 May 13;115(19):3997-4005. PMID:20110424 doi:10.1182/blood-2009-04-216069
8. ↑ Astarita JL, Cremasco V, Fu J, Darnell MC, Peck JR, Nieves-Bonilla JM, Song K, Kondo Y, Woodruff MC, Gogineni A, Onder L, Ludewig B, Weimer RM, Carroll MC, Mooney DJ, Xia L, Turley SJ. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat Immunol. 2015 Jan;16(1):75-84. PMID:25347465 doi:10.1038/ni.3035
9. ↑ Brooks CL, Schietinger A, Borisova SN, Kufer P, Okon M, Hirama T, Mackenzie CR, Wang LX, Schreiber H, Evans SV. Antibody recognition of a unique tumor-specific glycopeptide antigen. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10056-61. Epub 2010 May 17. PMID:20479270