ID PDPN_MOUSE Reviewed; 172 AA. AC Q62011; A2A8J3; Q546R8; Q61612; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 02-SEP-2026, entry version 178. DE RecName: Full=Podoplanin {ECO:0000250|UniProtKB:Q86YL7}; DE AltName: Full=Glycoprotein 38 {ECO:0000303|PubMed:1402691}; DE Short=Gp38 {ECO:0000303|PubMed:1402691}; DE AltName: Full=OTS-8 {ECO:0000303|PubMed:2088477}; DE AltName: Full=PA2.26 antigen {ECO:0000303|PubMed:10574709}; DE AltName: Full=Transmembrane glycoprotein E11 {ECO:0000303|Ref.5}; DE Short=E11 {ECO:0000303|Ref.5}; DE Flags: Precursor; GN Name=Pdpn {ECO:0000312|MGI:MGI:103098}; GN Synonyms=Gp38 {ECO:0000303|PubMed:1402691}, Ots8; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2088477; RA Nose K., Saito H., Kuroki T.; RT "Isolation of a gene sequence induced later by tumor-promoting 12-O- RT tetradecanoylphorbol-13-acetate in mouse osteoblastic cells (MC3T3-E1) and RT expressed constitutively in ras-transformed cells."; RL Cell Growth Differ. 1:511-518(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; RX PubMed=1402691; DOI=10.1084/jem.176.5.1477; RA Farr A.G., Berry M.L., Kim A., Nelson A.J., Welch M.P., Aruffo A.; RT "Characterization and cloning of a novel glycoprotein expressed by stromal RT cells in T-dependent areas of peripheral lymphoid tissues."; RL J. Exp. Med. 176:1477-1482(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-30 AND 66-73, FUNCTION, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION. RX PubMed=10574709; DOI=10.1242/jcs.112.24.4601; RA Scholl F.G., Gamallo C., Vilaro S., Quintanilla M.; RT "Identification of PA2.26 antigen as a novel cell-surface mucin-type RT glycoprotein that induces plasma membrane extensions and increased motility RT in keratinocytes."; RL J. Cell Sci. 112:4601-4613(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION. RC TISSUE=Kidney; RX PubMed=12032185; DOI=10.1093/ndt/17.6.978; RA Boucherot A., Schreiber R., Pavenstaedt H., Kunzelmann K.; RT "Cloning and expression of the mouse glomerular podoplanin homologue RT gp38P."; RL Nephrol. Dial. Transplant. 17:978-984(2002). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=129/Sv; RA Lu Y., Zhang J., Harris M.A., Harris S.E., Bonewald L., Feng J.; RT "Cloning and characterization studies of mouse E11 gene and its spatial and RT temporal expression pattern during development."; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Visual cortex; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=12654292; DOI=10.1016/s0012-1606(02)00098-2; RA Ramirez M.I., Millien G., Hinds A., Cao Y., Seldin D.C., Williams M.C.; RT "T1alpha, a lung type I cell differentiation gene, is required for normal RT lung cell proliferation and alveolus formation at birth."; RL Dev. Biol. 256:61-72(2003). RN [10] RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-34. RX PubMed=14522983; DOI=10.1074/jbc.m309935200; RA Kato Y., Fujita N., Kunita A., Sato S., Kaneko M., Osawa M., Tsuruo T.; RT "Molecular identification of aggrus/T1alpha as a platelet aggregation- RT inducing factor expressed in colorectal tumors."; RL J. Biol. Chem. 278:51599-51605(2003). RN [11] RP FUNCTION, AND GLYCOSYLATION. RX PubMed=15231832; DOI=10.1074/jbc.m407210200; RA Kaneko M., Kato Y., Kunita A., Fujita N., Tsuruo T., Osawa M.; RT "Functional sialylated O-glycan to platelet aggregation on Aggrus RT (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells."; RL J. Biol. Chem. 279:38838-38843(2004). RN [12] RP FUNCTION, AND INTERACTION WITH CLEC1B. RX PubMed=17616532; DOI=10.1074/jbc.m702327200; RA Suzuki-Inoue K., Kato Y., Inoue O., Kaneko M.K., Mishima K., Yatomi Y., RA Yamazaki Y., Narimatsu H., Ozaki Y.; RT "Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated RT platelet activation, by cancer cells."; RL J. Biol. Chem. 282:25993-26001(2007). RN [13] RP DISRUPTION PHENOTYPE, FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=20110424; DOI=10.1182/blood-2009-04-216069; RA Uhrin P., Zaujec J., Breuss J.M., Olcaydu D., Chrenek P., Stockinger H., RA Fuertbauer E., Moser M., Haiko P., Faessler R., Alitalo K., Binder B.R., RA Kerjaschki D.; RT "Novel function for blood platelets and podoplanin in developmental RT separation of blood and lymphatic circulation."; RL Blood 115:3997-4005(2010). RN [14] RP INDUCTION. RX PubMed=20962267; DOI=10.1091/mbc.e10-06-0489; RA Martin-Villar E., Fernandez-Munoz B., Parsons M., Yurrita M.M., Megias D., RA Perez-Gomez E., Jones G.E., Quintanilla M.; RT "Podoplanin associates with CD44 to promote directional cell migration."; RL Mol. Biol. Cell 21:4387-4399(2010). RN [15] RP PHOSPHORYLATION, AND MUTAGENESIS OF SER-167 AND SER-171. RX PubMed=23530051; DOI=10.1074/jbc.c112.446823; RA Krishnan H., Ochoa-Alvarez J.A., Shen Y., Nevel E., Lakshminarayanan M., RA Williams M.C., Ramirez M.I., Miller W.T., Goldberg G.S.; RT "Serines in the intracellular tail of podoplanin (PDPN) regulate cell RT motility."; RL J. Biol. Chem. 288:12215-12221(2013). RN [16] RP FUNCTION, AND DOMAIN. RX PubMed=25347465; DOI=10.1038/ni.3035; RA Astarita J.L., Cremasco V., Fu J., Darnell M.C., Peck J.R., RA Nieves-Bonilla J.M., Song K., Kondo Y., Woodruff M.C., Gogineni A., RA Onder L., Ludewig B., Weimer R.M., Carroll M.C., Mooney D.J., Xia L., RA Turley S.J.; RT "The CLEC-2-podoplanin axis controls the contractility of fibroblastic RT reticular cells and lymph node microarchitecture."; RL Nat. Immunol. 16:75-84(2015). RN [17] RP DEVELOPMENTAL STAGE. RX PubMed=28179430; DOI=10.1161/circresaha.116.308825; RA Morooka N., Futaki S., Sato-Nishiuchi R., Nishino M., Totani Y., RA Shimono C., Nakano I., Nakajima H., Mochizuki N., Sekiguchi K.; RT "Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel RT Remodeling."; RL Circ. Res. 120:1276-1288(2017). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 76-84 IN COMPLEX WITH RP IMMUNOGLOBULIN. RX PubMed=20479270; DOI=10.1073/pnas.0915176107; RA Brooks C.L., Schietinger A., Borisova S.N., Kufer P., Okon M., Hirama T., RA Mackenzie C.R., Wang L.X., Schreiber H., Evans S.V.; RT "Antibody recognition of a unique tumor-specific glycopeptide antigen."; RL Proc. Natl. Acad. Sci. U.S.A. 107:10056-10061(2010). CC -!- FUNCTION: Mediates effects on cell migration and adhesion through its CC different partners. During development plays a role in blood and CC lymphatic vessels separation by binding CLEC1B, triggering CLEC1B CC activation in platelets and leading to platelet activation and/or CC aggregation (PubMed:14522983, PubMed:15231832, PubMed:17616532, CC PubMed:20110424). Interaction with CD9, on the contrary, attenuates CC platelet aggregation and pulmonary metastasis induced by PDPN. Mediates CC effects on cell migration and adhesion through its different partners. CC Through MSN or EZR interaction promotes epithelial-mesenchymal CC transition (EMT) leading to ERZ phosphorylation and triggering RHOA CC activation leading to cell migration increase and invasiveness. CC Interaction with CD44 promotes directional cell migration in epithelial CC and tumor cells (By similarity). In lymph nodes (LNs), controls CC fibroblastic reticular cells (FRCs) adhesion to the extracellular CC matrix (ECM) and contraction of the actomyosin by maintaining ERM CC proteins (EZR; MSN and RDX) and MYL9 activation through association CC with unknown transmembrane proteins. Engagement of CLEC1B by PDPN CC promotes FRCs relaxation by blocking lateral membrane interactions CC leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 CC activation (PubMed:25347465). Through binding with LGALS8 may CC participate in connection of the lymphatic endothelium to the CC surrounding extracellular matrix (By similarity). In keratinocytes, CC induces changes in cell morphology showing an elongated shape, numerous CC membrane protrusions, major reorganization of the actin cytoskeleton, CC increased motility and decreased cell adhesion (PubMed:10574709). CC Controls invadopodia stability and maturation leading to efficient CC degradation of the extracellular matrix (ECM) in tumor cells through CC modulation of RHOC activity in order to activate ROCK1/ROCK2 and CC LIMK1/LIMK2 and inactivation of CFL1 (By similarity). Required for CC normal lung cell proliferation and alveolus formation at birth CC (PubMed:12654292). Does not function as a water channel or as a CC regulator of aquaporin-type water channels (By similarity). Does not CC have any effect on folic acid or amino acid transport CC (PubMed:12032185). {ECO:0000250|UniProtKB:Q86YL7, CC ECO:0000269|PubMed:10574709, ECO:0000269|PubMed:12032185, CC ECO:0000269|PubMed:12654292, ECO:0000269|PubMed:14522983, CC ECO:0000269|PubMed:15231832, ECO:0000269|PubMed:17616532, CC ECO:0000269|PubMed:20110424, ECO:0000269|PubMed:25347465}. CC -!- SUBUNIT: Homodimer. Interacts with CLEC1B; the interaction is CC independent of CLEC1B glycosylation and activates CLEC1B; the CC interaction is dependent of sialic acid on O-glycans (PubMed:17616532). CC Interacts with CD9; this interaction is homophilic and attenuates CC platelet aggregation and pulmonary metastasis induced by PDPN. CC Interacts with LGALS8; the interaction is glycosylation-dependent; may CC participate in connection of the lymphatic endothelium to the CC surrounding extracellular matrix. Interacts with HSPA9. Interacts (via CC extracellular domain) with CD44; this interaction is required for PDPN- CC mediated directional migration and regulation of lamellipodia CC extension/stabilization during cell spreading and migration. Interacts CC (via cytoplasmic domain) with MSN and EZR; activates RHOA and promotes CC epithelial-mesenchymal transition. Interacts with CCL21; relocalized CC PDPN to the basolateral membrane (By similarity). CC {ECO:0000250|UniProtKB:Q86YL7, ECO:0000269|PubMed:17616532}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10574709}; Single- CC pass type I membrane protein {ECO:0000255}. Cell projection, CC lamellipodium membrane {ECO:0000269|PubMed:10574709}; Single-pass type CC I membrane protein {ECO:0000269|PubMed:10574709}. Cell projection, CC filopodium membrane {ECO:0000269|PubMed:10574709}; Single-pass type I CC membrane protein {ECO:0000255}. Cell projection, microvillus membrane CC {ECO:0000269|PubMed:10574709}; Single-pass type I membrane protein CC {ECO:0000255}. Cell projection, ruffle membrane CC {ECO:0000269|PubMed:10574709}; Single-pass type I membrane protein CC {ECO:0000255}. Membrane raft {ECO:0000250|UniProtKB:Q86YL7}. Apical CC cell membrane {ECO:0000250|UniProtKB:Q86YL7}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q86YL7}. Cell projection, invadopodium CC {ECO:0000250|UniProtKB:Q86YL7}. Note=Localized to actin-rich microvilli CC and plasma membrane projections such as filopodia, lamellipodia and CC ruffles (PubMed:10574709). Association to the lipid rafts is required CC for PDPN-induced epithelial to mesenchymal transition (EMT). CC Colocalizes with CD9 in tetraspanin microdomains. Localized at CC invadopodium adhesion rings in tumor cell. Association to the lipid CC rafts is essential for PDPN recruitment to invadopodia and ECM CC degradation (By similarity). {ECO:0000250|UniProtKB:Q86YL7, CC ECO:0000269|PubMed:10574709}. CC -!- TISSUE SPECIFICITY: Detected at high levels in lung and brain, at lower CC levels in kidney, stomach, liver, spleen and esophagus, and not CC detected in skin and small intestine. Expressed in epithelial cells of CC choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells CC and in endothelia of lymphatic vessels. Also expressed in stromal cells CC of peripheral lymphoid tissue and thymic epithelial cells. Detected in CC carcinoma cell lines and cultured fibroblasts. Expressed at higher CC levels in colon carcinomas than in normal colon tissue. CC {ECO:0000269|PubMed:10574709, ECO:0000269|PubMed:12032185, CC ECO:0000269|PubMed:14522983}. CC -!- DEVELOPMENTAL STAGE: Expressed in mesenteric lymphatic endothelial CC cells at 16.5 and 18.5 dpc (at protein level) (PubMed:28179430). At CC 12.5 dpc and 13.5 dpc is expressed in the endothelial cells of forming CC lymph sacs (PubMed:20110424). {ECO:0000269|PubMed:20110424, CC ECO:0000269|PubMed:28179430}. CC -!- INDUCTION: Down-regulated by treatment with puromycin aminonucleoside CC (PubMed:12032185). Up-regulated during progression to highly aggressive CC tumors and during epithelial-mesenchymal transition (EMT) CC (PubMed:20962267). {ECO:0000269|PubMed:12032185, CC ECO:0000269|PubMed:20962267}. CC -!- DOMAIN: The cytoplasmic domain controls FRC elongation but is CC dispensable for contraction (PubMed:25347465). The cytoplasmic domain CC is essential for recruitment to invadopodia and ECM degradation (By CC similarity). {ECO:0000250|UniProtKB:Q86YL7, CC ECO:0000269|PubMed:25347465}. CC -!- PTM: Extensively O-glycosylated. Contains sialic acid residues. O- CC glycosylation is necessary for platelet aggregation activity. CC Disialylated at Thr-52; sialic acid is critical for platelet- CC aggregating activity and for CLEC1B interaction (By similarity). CC {ECO:0000250|UniProtKB:Q86YL7, ECO:0000269|PubMed:10574709, CC ECO:0000269|PubMed:15231832}. CC -!- PTM: Phosphorylated by PKA; decreases cell migration. CC {ECO:0000269|PubMed:23530051}. CC -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:Q64294}. CC -!- DISRUPTION PHENOTYPE: Mice die at birth of respiratory failure due to a CC low number of attenuated type I cells, narrow and irregular air spaces, CC and defective formation of alveolar saccules (PubMed:12654292). CC Knockout Pdpn mice neonates are smaller, and approximately 55% died CC during the first postnatal week. However, approximately 20% survived, CC had normal weights and life spans, and are fertile (PubMed:20110424). CC {ECO:0000269|PubMed:12654292, ECO:0000269|PubMed:20110424}. CC -!- SIMILARITY: Belongs to the podoplanin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M73748; AAA39866.1; -; mRNA. DR EMBL; M96645; AAA37724.1; -; mRNA. DR EMBL; AJ250246; CAB58997.1; -; mRNA. DR EMBL; AJ297944; CAC16152.1; -; mRNA. DR EMBL; AY115493; AAM66761.1; -; Genomic_DNA. DR EMBL; AK158855; BAE34695.1; -; mRNA. DR EMBL; AL611982; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC026551; AAH26551.1; -; mRNA. DR CCDS; CCDS38943.1; -. DR PIR; A54560; A54560. DR RefSeq; NP_001277751.1; NM_001290822.2. DR RefSeq; NP_034459.2; NM_010329.4. DR PDB; 3IET; X-ray; 2.20 A; Q/X=76-84. DR PDB; 6LZ4; X-ray; 2.49 A; C/F=38-51. DR AlphaFoldDB; Q62011; -. DR SMR; Q62011; -. DR FunCoup; Q62011; 53. DR IntAct; Q62011; 1. DR STRING; 10090.ENSMUSP00000030317; -. DR GlyCosmos; Q62011; 19 sites, No reported glycans. DR GlyGen; Q62011; 19 sites, 1 N-linked glycan (1 site). DR iPTMnet; Q62011; -. DR PhosphoSitePlus; Q62011; -. DR PaxDb; 10090-ENSMUSP00000030317; -. DR ProteomicsDB; 288024; -. DR Pumba; Q62011; -. DR ABCD; Q62011; 18 sequenced antibodies. DR Antibodypedia; 764; 1374 antibodies from 52 providers. DR DNASU; 14726; -. DR Ensembl; ENSMUST00000030317.14; ENSMUSP00000030317.8; ENSMUSG00000028583.15. DR GeneID; 14726; -. DR KEGG; mmu:14726; -. DR UCSC; uc008vqa.2; mouse. DR AGR; MGI:103098; -. DR CTD; 10630; -. DR MGI; MGI:103098; Pdpn. DR VEuPathDB; HostDB:ENSMUSG00000028583; -. DR eggNOG; ENOG502QRWU; Eukaryota. DR GeneTree; ENSGT00390000000013; -. DR InParanoid; Q62011; -. DR OMA; SAWLWIP; -. DR OrthoDB; 9633724at2759; -. DR PhylomeDB; Q62011; -. DR Reactome; R-MMU-114604; GPVI-mediated activation cascade. DR BioGRID-ORCS; 14726; 0 hits in 79 CRISPR screens. DR EvolutionaryTrace; Q62011; -. DR PRO; PR:Q62011; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q62011; protein. DR Bgee; ENSMUSG00000028583; Expressed in yolk sac and 86 other cell types or tissues. DR ExpressionAtlas; Q62011; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0030054; C:cell junction; ISO:GO_Central. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI. DR GO; GO:0030175; C:filopodium; IDA:UniProtKB. DR GO; GO:0031527; C:filopodium membrane; ISS:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0031258; C:lamellipodium membrane; ISS:UniProtKB. DR GO; GO:0061851; C:leading edge of lamellipodium; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; EXP:UniProtKB. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISO:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; ISS:UniProtKB. DR GO; GO:0019956; F:chemokine binding; ISO:GO_Central. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB. DR GO; GO:0070252; P:actin-mediated cell contraction; IDA:UniProtKB. DR GO; GO:0007155; P:cell adhesion; ISO:MGI. DR GO; GO:0016477; P:cell migration; IMP:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI. DR GO; GO:0048286; P:lung alveolus development; IMP:MGI. DR GO; GO:0030324; P:lung development; IMP:MGI. DR GO; GO:0048535; P:lymph node development; IMP:UniProtKB. DR GO; GO:0001946; P:lymphangiogenesis; IMP:MGI. DR GO; GO:0060838; P:lymphatic endothelial cell fate commitment; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:2000147; P:positive regulation of cell motility; IMP:MGI. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB. DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; ISS:UniProtKB. DR GO; GO:0010572; P:positive regulation of platelet activation; ISO:GO_Central. DR GO; GO:1901731; P:positive regulation of platelet aggregation; IDA:UniProtKB. DR GO; GO:0006693; P:prostaglandin metabolic process; IMP:MGI. DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:MGI. DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; ISS:UniProtKB. DR GO; GO:1904328; P:regulation of myofibroblast contraction; IMP:UniProtKB. DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IMP:MGI. DR GO; GO:0035239; P:tube morphogenesis; ISO:MGI. DR GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT. DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB. DR InterPro; IPR052684; Podoplanin_domain. DR PANTHER; PTHR47390; PODOPLANIN; 1. DR PANTHER; PTHR47390:SF1; PODOPLANIN; 1. DR Pfam; PF05808; Podoplanin; 1. DR PDBsum; 3IET; -. DR PDBsum; 6LZ4; -. PE 1: Evidence at protein level; KW 3D-structure; Cell junction; Cell membrane; Cell projection; Cell shape; KW Developmental protein; Direct protein sequencing; Glycoprotein; Membrane; KW Reference proteome; Sialic acid; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..22 FT /evidence="ECO:0000250|UniProtKB:Q86YL7" FT CHAIN 23..172 FT /note="Podoplanin" FT /id="PRO_0000021352" FT TOPO_DOM 23..141 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 142..162 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 163..172 FT /note="Cytoplasmic" FT REGION 49..132 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 143..147 FT /note="Requires for dimerization and lipidd rafts FT association" FT /evidence="ECO:0000250|UniProtKB:Q86YL7" FT REGION 164..165 FT /note="Requires for interaction with MSN and EZR" FT /evidence="ECO:0000250|UniProtKB:Q86YL7" FT COMPBIAS 51..63 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 72..81 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 90..99 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 100..109 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 110..132 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 37 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 51 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 52 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:Q86YL7" FT CARBOHYD 53 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 56 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 60 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 63 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 71 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 77 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 85 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000255" FT CARBOHYD 86 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 87 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000255" FT CARBOHYD 89 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 90 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000255" FT CARBOHYD 100 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 101 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 102 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 107 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 115 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT MUTAGEN 34 FT /note="T->A: Eliminates platelet aggregation activity." FT /evidence="ECO:0000269|PubMed:14522983" FT MUTAGEN 167 FT /note="S->A: 50% decrease of cell growth; when associated FT with A-171. 50% increase of cell migration; when associated FT with A-171." FT /evidence="ECO:0000269|PubMed:23530051" FT MUTAGEN 167 FT /note="S->D: Does not significantly increase cell motility; FT when associated with D-171. Does not significantly decrease FT cell growth; when associated with A-171." FT /evidence="ECO:0000269|PubMed:23530051" FT MUTAGEN 171 FT /note="S->A: 50% decrease of cell growth; when associated FT with A-167. 50% increase of cell migration; when associated FT with A-167." FT /evidence="ECO:0000269|PubMed:23530051" FT MUTAGEN 171 FT /note="S->D: Does not significantly increase cell motility; FT when associated with D-171. Does not significantly decrease FT cell growth; when associated with A-171." FT /evidence="ECO:0000269|PubMed:23530051" FT CONFLICT 29..31 FT /note="EDD -> KNN (in Ref. 2; AAA37724)" FT /evidence="ECO:0000305" FT CONFLICT 38..39 FT /note="GD -> EN (in Ref. 2; AAA37724)" FT /evidence="ECO:0000305" FT CONFLICT 170..172 FT /note="FSP -> SRPKELNRTGCSPNTSENKRASNLPCSPSSSCGGR (in Ref. FT 1; AAA39866)" FT /evidence="ECO:0000305" FT HELIX 77..80 FT /evidence="ECO:0007829|PDB:3IET" FT HELIX 81..83 FT /evidence="ECO:0007829|PDB:3IET" SQ SEQUENCE 172 AA; 18233 MW; C035ED251918CE6F CRC64; MWTVPVLFWV LGSVWFWDSA QGGTIGVNED DIVTPGTGDG MVPPGIEDKI TTTGATGGLN ESTGKAPLVP TQRERGTKPP LEELSTSATS DHDHREHEST TTVKVVTSHS VDKKTSHPNR DNAGDETQTT DKKDGLPVVT LVGIIVGVLL AIGFVGGIFI VVMKKISGRF SP //