PDPN_HUMAN
ID PDPN_HUMAN Reviewed; 162 AA.
AC Q86YL7; A9Z1Y2; B2R6J8; E9PB68; F6QWX5; O60836; O95128; Q7L375; Q8NBQ8;
AC Q8NBR3;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Podoplanin {ECO:0000303|Ref.9};
DE AltName: Full=Aggrus {ECO:0000303|Ref.3};
DE AltName: Full=Glycoprotein 36;
DE Short=Gp36 {ECO:0000303|PubMed:10393083};
DE AltName: Full=PA2.26 antigen {ECO:0000303|PubMed:15515019};
DE AltName: Full=T1-alpha {ECO:0000250|UniProtKB:Q64294};
DE Short=T1A {ECO:0000250|UniProtKB:Q64294};
DE Contains:
DE RecName: Full=29kDa cytosolic podoplanin intracellular domain {ECO:0000303|PubMed:24275092};
DE Short=PICD {ECO:0000303|PubMed:24275092};
DE Flags: Precursor;
GN Name=PDPN {ECO:0000312|EMBL:AAH14668.2};
GN Synonyms=GP36 {ECO:0000303|PubMed:10393083}; ORFNames=PSEC0003, PSEC0025;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD01900.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND VARIANT
RP GLY-147.
RX PubMed=9651190; DOI=10.1165/ajrcmb.19.1.2953;
RA Ma T., Yang B., Matthay M.A., Verkman A.S.;
RT "Evidence against a role of mouse, rat, and two cloned human T1alpha
RT isoforms as a water channel or a regulator of aquaporin-type water
RT channels.";
RL Am. J. Respir. Cell Mol. Biol. 19:143-149(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:CAA12352.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION,
RP AND VARIANT GLY-147.
RC TISSUE=Placenta {ECO:0000312|EMBL:CAA12352.1};
RX PubMed=10393083; DOI=10.1042/bj3410277;
RA Zimmer G., Oeffner F., von Messling V., Tschernig T., Groene H.-J.,
RA Klenk H.-D., Herrler G.;
RT "Cloning and characterization of gp36, a human mucin-type glycoprotein
RT preferentially expressed in vascular endothelium.";
RL Biochem. J. 341:277-284(1999).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAM73655.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-147.
RC TISSUE=Lung {ECO:0000312|EMBL:BAD04046.1};
RA Kato Y., Fujita N., Tsuruo T.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH14668.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT GLY-147.
RC TISSUE=Eye {ECO:0000312|EMBL:AAH14668.2};
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 [6] {ECO:0000305, ECO:0000312|EMBL:AAO22143.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-162 (ISOFORM 3), FUNCTION, TISSUE
RP SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=15515019; DOI=10.1002/ijc.20656;
RA Martin-Villar E., Scholl F.G., Gamallo C., Yurrita M.M., Munoz-Guerra M.,
RA Cruces J., Quintanilla M.;
RT "Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small
RT membrane mucin induced in oral squamous cell carcinomas.";
RL Int. J. Cancer 113:899-910(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-162 (ISOFORM 3), AND VARIANT
RP GLY-147.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-162 (ISOFORM 4), AND VARIANT
RP GLY-147.
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [9] {ECO:0000305, ECO:0000312|EMBL:AAM73655.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-162 (ISOFORM 3), AND VARIANT GLY-147.
RC TISSUE=Kidney {ECO:0000312|EMBL:AAM73655.1};
RA Kowalski H., Kalt R., Auer H., Dontscho K.;
RT "Molecular cloning and characterization of human podoplanin, a small mucin-
RT type glycoprotein of glomerular podocytes.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 23-57, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY,
RP AND GLYCOSYLATION AT THR-52.
RX PubMed=17222411; DOI=10.1016/j.febslet.2006.12.044;
RA Kaneko M.K., Kato Y., Kameyama A., Ito H., Kuno A., Hirabayashi J.,
RA Kubota T., Amano K., Chiba Y., Hasegawa Y., Sasagawa I., Mishima K.,
RA Narimatsu H.;
RT "Functional glycosylation of human podoplanin: glycan structure of platelet
RT aggregation-inducing factor.";
RL FEBS Lett. 581:331-336(2007).
RN [11]
RP PROTEIN SEQUENCE OF 151-156, PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24275092; DOI=10.1016/j.biocel.2013.11.016;
RA Yurrita M.M., Fernandez-Munoz B., Del Castillo G., Martin-Villar E.,
RA Renart J., Quintanilla M.;
RT "Podoplanin is a substrate of presenilin-1/gamma-secretase.";
RL Int. J. Biochem. Cell Biol. 46:68-75(2014).
RN [12] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-52.
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 [13]
RP INTERACTION WITH CCL21, AND SUBCELLULAR LOCATION.
RX PubMed=14978162; DOI=10.1097/01.asn.0000113316.52371.2e;
RA Kerjaschki D., Regele H.M., Moosberger I., Nagy-Bojarski K.,
RA Watschinger B., Soleiman A., Birner P., Krieger S., Hovorka A.,
RA Silberhumer G., Laakkonen P., Petrova T., Langer B., Raab I.;
RT "Lymphatic neoangiogenesis in human kidney transplants is associated with
RT immunologically active lymphocytic infiltrates.";
RL J. Am. Soc. Nephrol. 15:603-612(2004).
RN [14] {ECO:0000305}
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 [15]
RP MUTAGENESIS OF 154-ARG--ARG-159; 154-ARG-LYS-155 AND ARG-159, SUBCELLULAR
RP LOCATION, FUNCTION, REGION, AND INTERACTION WITH MSN AND EZR.
RX PubMed=17046996; DOI=10.1242/jcs.03218;
RA Martin-Villar E., Megias D., Castel S., Yurrita M.M., Vilaro S.,
RA Quintanilla M.;
RT "Podoplanin binds ERM proteins to activate RhoA and promote epithelial-
RT mesenchymal transition.";
RL J. Cell Sci. 119:4541-4553(2006).
RN [16]
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 [17]
RP FUNCTION, INTERACTION WITH CLEC1B, AND SUBCELLULAR LOCATION.
RX PubMed=18215137; DOI=10.1042/bj20071216;
RA Christou C.M., Pearce A.C., Watson A.A., Mistry A.R., Pollitt A.Y.,
RA Fenton-May A.E., Johnson L.A., Jackson D.G., Watson S.P., O'Callaghan C.A.;
RT "Renal cells activate the platelet receptor CLEC-2 through podoplanin.";
RL Biochem. J. 411:133-140(2008).
RN [18]
RP INTERACTION WITH CD9, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=18541721; DOI=10.1182/blood-2007-11-124693;
RA Nakazawa Y., Sato S., Naito M., Kato Y., Mishima K., Arai H., Tsuruo T.,
RA Fujita N.;
RT "Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet
RT aggregation and suppresses pulmonary metastasis.";
RL Blood 112:1730-1739(2008).
RN [19]
RP INTERACTION WITH LGALS8, AND FUNCTION.
RX PubMed=19268462; DOI=10.1016/j.yexcr.2009.02.021;
RA Cueni L.N., Detmar M.;
RT "Galectin-8 interacts with podoplanin and modulates lymphatic endothelial
RT cell functions.";
RL Exp. Cell Res. 315:1715-1723(2009).
RN [20]
RP SUBCELLULAR LOCATION, INTERACTION WITH CD44, MUTAGENESIS OF
RP 154-ARG--ARG-159, AND FUNCTION.
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 [21]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-137, FUNCTION, REGION, AND
RP SUBUNIT.
RX PubMed=21376833; DOI=10.1016/j.biocel.2011.02.010;
RA Fernandez-Munoz B., Yurrita M.M., Martin-Villar E., Carrasco-Ramirez P.,
RA Megias D., Renart J., Quintanilla M.;
RT "The transmembrane domain of podoplanin is required for its association
RT with lipid rafts and the induction of epithelial-mesenchymal transition.";
RL Int. J. Biochem. Cell Biol. 43:886-896(2011).
RN [22]
RP INTERACTION WITH HSPA9.
RX PubMed=23541579; DOI=10.1016/j.bbrc.2013.03.057;
RA Tsuneki M., Maruyama S., Yamazaki M., Xu B., Essa A., Abe T., Babkair H.,
RA Cheng J., Yamamoto T., Saku T.;
RT "Extracellular heat shock protein A9 is a novel interaction partner of
RT podoplanin in oral squamous cell carcinoma cells.";
RL Biochem. Biophys. Res. Commun. 434:124-130(2013).
RN [23]
RP SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF GLY-137 AND
RP 154-ARG--ARG-159, AND DOMAIN.
RX PubMed=25486435; DOI=10.1038/onc.2014.388;
RA Martin-Villar E., Borda-d'Agua B., Carrasco-Ramirez P., Renart J.,
RA Parsons M., Quintanilla M., Jones G.E.;
RT "Podoplanin mediates ECM degradation by squamous carcinoma cells through
RT control of invadopodia stability.";
RL Oncogene 34:4531-4544(2015).
RN [24] {ECO:0007744|PDB:3WSR}
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 38-54 IN COMPLEX WITH CLEC1B, AND
RP GLYCOSYLATION AT THR-52.
RX PubMed=25458834; DOI=10.1016/j.str.2014.09.009;
RA Nagae M., Morita-Matsumoto K., Kato M., Kaneko M.K., Kato Y., Yamaguchi Y.;
RT "A platform of C-type lectin-like receptor CLEC-2 for binding O-
RT glycosylated podoplanin and nonglycosylated rhodocytin.";
RL Structure 22:1711-1721(2014).
RN [25] {ECO:0007744|PDB:4YO0}
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 38-51.
RX PubMed=26872787; DOI=10.1242/jcs.176685;
RA Fujii Y., Matsunaga Y., Arimori T., Kitago Y., Ogasawara S., Kaneko M.K.,
RA Kato Y., Takagi J.;
RT "Tailored placement of a turn-forming PA tag into the structured domain of
RT a protein to probe its conformational state.";
RL J. Cell Sci. 129:1512-1522(2016).
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:18215137, PubMed:17222411). Interaction with CD9, on the
CC contrary, attenuates platelet aggregation induced by PDPN
CC (PubMed:18541721). Through MSN or EZR interaction promotes epithelial-
CC mesenchymal transition (EMT) leading to ERZ phosphorylation and
CC triggering RHOA activation leading to cell migration increase and
CC invasiveness (PubMed:17046996, PubMed:21376833). Interaction with CD44
CC promotes directional cell migration in epithelial and tumor cells
CC (PubMed:20962267). In lymph nodes (LNs), controls fibroblastic
CC reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and
CC contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and
CC RDX) and MYL9 activation through association with unknown transmembrane
CC proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by
CC blocking lateral membrane interactions leading to reduction of ERM
CC proteins (EZR; MSN and RDX) and MYL9 activation (By similarity).
CC Through binding with LGALS8 may participate in connection of the
CC lymphatic endothelium to the surrounding extracellular matrix
CC (PubMed:19268462). In keratinocytes, induces changes in cell morphology
CC showing an elongated shape, numerous membrane protrusions, major
CC reorganization of the actin cytoskeleton, increased motility and
CC decreased cell adhesion (PubMed:15515019). Controls invadopodia
CC stability and maturation leading to efficient degradation of the
CC extracellular matrix (ECM) in tumor cells through modulation of RHOC
CC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and
CC inactivation of CFL1 (PubMed:25486435). Required for normal lung cell
CC proliferation and alveolus formation at birth (By similarity). Does not
CC function as a water channel or as a regulator of aquaporin-type water
CC channels (PubMed:9651190). Does not have any effect on folic acid or
CC amino acid transport (By similarity). {ECO:0000250|UniProtKB:Q62011,
CC ECO:0000269|PubMed:14522983, ECO:0000269|PubMed:15231832,
CC ECO:0000269|PubMed:15515019, ECO:0000269|PubMed:17046996,
CC ECO:0000269|PubMed:17222411, ECO:0000269|PubMed:17616532,
CC ECO:0000269|PubMed:18215137, ECO:0000269|PubMed:18541721,
CC ECO:0000269|PubMed:19268462, ECO:0000269|PubMed:20962267,
CC ECO:0000269|PubMed:21376833, ECO:0000269|PubMed:25486435,
CC ECO:0000269|PubMed:9651190}.
CC -!- SUBUNIT: Homodimer (PubMed:21376833). Interacts with CLEC1B; the
CC interaction is independent of CLEC1B glycosylation and activates
CC CLEC1B; the interaction is dependent of sialic acid on O-glycans
CC (PubMed:18215137, PubMed:17616532, PubMed:25458834). Interacts with
CC CD9; this interaction is homophilic and attenuates platelet aggregation
CC and pulmonary metastasis induced by PDPN (PubMed:18541721). Interacts
CC with LGALS8; the interaction is glycosylation-dependent; may
CC participate in connection of the lymphatic endothelium to the
CC surrounding extracellular matrix (PubMed:19268462). Interacts with
CC HSPA9 (PubMed:23541579). Interacts (via extracellular domain) with
CC CD44; this interaction is required for PDPN-mediated directional
CC migration and regulation of lamellipodia extension/stabilization during
CC cell spreading and migration (PubMed:20962267). Interacts (via
CC cytoplasmic domain) with MSN and EZR; activates RHOA and promotes
CC epithelial-mesenchymal transition (PubMed:17046996). Interacts with
CC CCL21; relocalized PDPN to the basolateral membrane (PubMed:14978162).
CC {ECO:0000269|PubMed:14978162, ECO:0000269|PubMed:17046996,
CC ECO:0000269|PubMed:17616532, ECO:0000269|PubMed:18215137,
CC ECO:0000269|PubMed:18541721, ECO:0000269|PubMed:19268462,
CC ECO:0000269|PubMed:20962267, ECO:0000269|PubMed:21376833,
CC ECO:0000269|PubMed:23541579, ECO:0000269|PubMed:25458834}.
CC -!- INTERACTION:
CC Q86YL7; Q9P126-1: CLEC1B; NbExp=2; IntAct=EBI-723160, EBI-16130833;
CC Q86YL7; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-723160, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: [Podoplanin]: Membrane
CC {ECO:0000269|PubMed:17046996, ECO:0000269|PubMed:20962267,
CC ECO:0000305|PubMed:18215137}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q62011}. Cell projection, lamellipodium membrane
CC {ECO:0000269|PubMed:17046996, ECO:0000269|PubMed:20962267}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:Q62011}. Cell
CC projection, filopodium membrane {ECO:0000269|PubMed:17046996}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:Q62011}. Cell
CC projection, microvillus membrane {ECO:0000269|PubMed:17046996}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:Q62011}. Cell
CC projection, ruffle membrane {ECO:0000269|PubMed:17046996}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:Q62011}. Membrane raft
CC {ECO:0000269|PubMed:21376833}. Apical cell membrane
CC {ECO:0000269|PubMed:20962267}. Basolateral cell membrane
CC {ECO:0000269|PubMed:14978162}. Cell projection, invadopodium
CC {ECO:0000269|PubMed:25486435}. Note=Localized to actin-rich microvilli
CC and plasma membrane projections such as filopodia, lamellipodia and
CC ruffles (By similarity). Association to the lipid rafts is required for
CC PDPN-induced epithelial to mesenchymal transition (EMT)
CC (PubMed:21376833). Colocalizes with CD9 in tetraspanin microdomains
CC (PubMed:18541721). Localized at invadopodium adhesion rings in tumor
CC cell. Association to the lipid rafts is essential for PDPN recruitment
CC to invadopodia and ECM degradation (PubMed:25486435).
CC {ECO:0000250|UniProtKB:Q62011, ECO:0000269|PubMed:18541721,
CC ECO:0000269|PubMed:21376833, ECO:0000269|PubMed:25486435}.
CC -!- SUBCELLULAR LOCATION: [29kDa cytosolic podoplanin intracellular
CC domain]: Cytoplasm, cytosol {ECO:0000269|PubMed:24275092}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1 {ECO:0000269|PubMed:9651190}; Synonyms=hT1alpha-2
CC {ECO:0000303|PubMed:9651190};
CC IsoId=Q86YL7-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9651190}; Synonyms=hT1alpha-1
CC {ECO:0000303|PubMed:9651190};
CC IsoId=Q86YL7-2; Sequence=VSP_051949, VSP_051950, VSP_051951;
CC Name=3;
CC IsoId=Q86YL7-3; Sequence=VSP_035753;
CC Name=4;
CC IsoId=Q86YL7-4; Sequence=VSP_035753, VSP_035754;
CC Name=5;
CC IsoId=Q86YL7-5; Sequence=VSP_046799, VSP_046800;
CC Name=6;
CC IsoId=Q86YL7-6; Sequence=VSP_046799;
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, lung, skeletal muscle
CC and brain. Weakly expressed in brain, kidney and liver. In placenta,
CC expressed on the apical plasma membrane of endothelium. In lung,
CC expressed in alveolar epithelium. Up-regulated in colorectal tumors and
CC expressed in 25% of early oral squamous cell carcinomas.
CC {ECO:0000269|PubMed:10393083, ECO:0000269|PubMed:14522983,
CC ECO:0000269|PubMed:15515019}.
CC -!- DOMAIN: The cytoplasmic domain controls FRC elongation but is
CC dispensable for contraction (By similarity). The cytoplasmic domain is
CC essential for recruitment to invadopodia and ECM degradation
CC (PubMed:25486435). {ECO:0000250|UniProtKB:Q62011,
CC ECO:0000269|PubMed:25486435}.
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 (PubMed:17222411,
CC PubMed:25458834). {ECO:0000269|PubMed:10393083,
CC ECO:0000269|PubMed:15231832, ECO:0000269|PubMed:15515019,
CC ECO:0000269|PubMed:17222411, ECO:0000269|PubMed:25458834}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:Q64294}.
CC -!- PTM: Cleaved by a metalloprotease within its extracellular (EC) domain,
CC generating a membrane-bound C-terminal fragment (PCTF33) and an
CC extracellular fragment. The resulting membrane-bound C-terminal
CC fragment (PCTF33) is further processed between Val-150 and Val-151 by
CC PSEN1/gamma-secretase generating the intracellular domain of podoplanin
CC (PICD). {ECO:0000269|PubMed:24275092}.
CC -!- SIMILARITY: Belongs to the podoplanin family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM73655.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO22143.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC11550.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC11557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG35495.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF030427; AAD01899.1; -; mRNA.
DR EMBL; AF030428; AAD01900.1; -; mRNA.
DR EMBL; AJ225022; CAA12352.1; -; mRNA.
DR EMBL; AB127958; BAD04046.1; -; mRNA.
DR EMBL; AL354712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014668; AAH14668.2; -; mRNA.
DR EMBL; BC022812; AAH22812.2; -; mRNA.
DR EMBL; AY194238; AAO22143.1; ALT_INIT; mRNA.
DR EMBL; AK312607; BAG35495.1; ALT_INIT; mRNA.
DR EMBL; AK075327; BAC11550.1; ALT_INIT; mRNA.
DR EMBL; AK075345; BAC11557.1; ALT_INIT; mRNA.
DR EMBL; AF390106; AAM73655.1; ALT_INIT; mRNA.
DR CCDS; CCDS30602.1; -. [Q86YL7-1]
DR CCDS; CCDS41266.1; -. [Q86YL7-4]
DR CCDS; CCDS44060.1; -. [Q86YL7-6]
DR CCDS; CCDS53270.1; -. [Q86YL7-5]
DR RefSeq; NP_001006625.1; NM_001006624.1. [Q86YL7-6]
DR RefSeq; NP_001006626.1; NM_001006625.1. [Q86YL7-5]
DR RefSeq; NP_006465.3; NM_006474.4. [Q86YL7-1]
DR RefSeq; NP_938203.2; NM_198389.2. [Q86YL7-4]
DR RefSeq; XP_006710358.1; XM_006710295.1. [Q86YL7-6]
DR PDB; 3WSR; X-ray; 1.91 A; C/D=38-54.
DR PDB; 4YO0; X-ray; 1.56 A; E/F=38-51.
DR PDB; 5XCV; X-ray; 2.14 A; C/F=38-51.
DR PDB; 7C94; X-ray; 2.84 A; C/F=67-84.
DR PDB; 7CQC; X-ray; 2.50 A; A=38-51.
DR PDB; 7CQD; X-ray; 3.20 A; A/B=38-51.
DR PDBsum; 3WSR; -.
DR PDBsum; 4YO0; -.
DR PDBsum; 5XCV; -.
DR PDBsum; 7C94; -.
DR PDBsum; 7CQC; -.
DR PDBsum; 7CQD; -.
DR AlphaFoldDB; Q86YL7; -.
DR SMR; Q86YL7; -.
DR BioGRID; 115874; 18.
DR DIP; DIP-61333N; -.
DR IntAct; Q86YL7; 6.
DR STRING; 9606.ENSP00000294489; -.
DR GlyGen; Q86YL7; 26 sites, 3 O-linked glycans (3 sites).
DR iPTMnet; Q86YL7; -.
DR PhosphoSitePlus; Q86YL7; -.
DR BioMuta; PDPN; -.
DR DMDM; 215274223; -.
DR EPD; Q86YL7; -.
DR jPOST; Q86YL7; -.
DR MassIVE; Q86YL7; -.
DR PaxDb; Q86YL7; -.
DR PeptideAtlas; Q86YL7; -.
DR PRIDE; Q86YL7; -.
DR ProteomicsDB; 19157; -.
DR ProteomicsDB; 27867; -.
DR ProteomicsDB; 70429; -. [Q86YL7-1]
DR ProteomicsDB; 70431; -. [Q86YL7-3]
DR ProteomicsDB; 70432; -. [Q86YL7-4]
DR ABCD; Q86YL7; 8 sequenced antibodies.
DR Antibodypedia; 764; 1284 antibodies from 51 providers.
DR DNASU; 10630; -.
DR Ensembl; ENST00000294489.10; ENSP00000294489.6; ENSG00000162493.17. [Q86YL7-3]
DR Ensembl; ENST00000376057.8; ENSP00000365225.4; ENSG00000162493.17. [Q86YL7-4]
DR Ensembl; ENST00000376061.8; ENSP00000365229.4; ENSG00000162493.17. [Q86YL7-6]
DR Ensembl; ENST00000475043.5; ENSP00000426063.1; ENSG00000162493.17. [Q86YL7-5]
DR Ensembl; ENST00000487038.5; ENSP00000427537.1; ENSG00000162493.17. [Q86YL7-6]
DR Ensembl; ENST00000513143.5; ENSP00000425304.1; ENSG00000162493.17. [Q86YL7-6]
DR Ensembl; ENST00000621990.5; ENSP00000478125.1; ENSG00000162493.17. [Q86YL7-1]
DR GeneID; 10630; -.
DR KEGG; hsa:10630; -.
DR MANE-Select; ENST00000621990.5; ENSP00000478125.1; NM_006474.5; NP_006465.4.
DR UCSC; uc001avc.4; human. [Q86YL7-1]
DR CTD; 10630; -.
DR DisGeNET; 10630; -.
DR GeneCards; PDPN; -.
DR HGNC; HGNC:29602; PDPN.
DR HPA; ENSG00000162493; Tissue enhanced (placenta).
DR MIM; 608863; gene.
DR neXtProt; NX_Q86YL7; -.
DR OpenTargets; ENSG00000162493; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR PharmGKB; PA142671187; -.
DR VEuPathDB; HostDB:ENSG00000162493; -.
DR eggNOG; ENOG502QRWU; Eukaryota.
DR GeneTree; ENSGT00390000000013; -.
DR HOGENOM; CLU_102220_0_0_1; -.
DR InParanoid; Q86YL7; -.
DR OrthoDB; 1303144at2759; -.
DR PhylomeDB; Q86YL7; -.
DR TreeFam; TF337068; -.
DR PathwayCommons; Q86YL7; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR SignaLink; Q86YL7; -.
DR BioGRID-ORCS; 10630; 7 hits in 1086 CRISPR screens.
DR ChiTaRS; PDPN; human.
DR GeneWiki; PDPN; -.
DR GenomeRNAi; 10630; -.
DR Pharos; Q86YL7; Tbio.
DR PRO; PR:Q86YL7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q86YL7; protein.
DR Bgee; ENSG00000162493; Expressed in tibia and 165 other tissues.
DR ExpressionAtlas; Q86YL7; baseline and differential.
DR Genevisible; Q86YL7; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0042995; C:cell projection; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IDA:UniProtKB.
DR GO; GO:0061851; C:leading edge of lamellipodium; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB.
DR GO; GO:0019956; F:chemokine binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0070252; P:actin-mediated cell contraction; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR GO; GO:0048535; P:lymph node development; ISS:UniProtKB.
DR GO; GO:0001946; P:lymphangiogenesis; ISS:UniProtKB.
DR GO; GO:0060838; P:lymphatic endothelial cell fate commitment; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; TAS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; IDA:UniProtKB.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; IMP:UniProtKB.
DR GO; GO:1904328; P:regulation of myofibroblast contraction; ISS:UniProtKB.
DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0055093; P:response to hyperoxia; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Cell shape; Cytoplasm; Developmental protein;
KW Direct protein sequencing; Glycoprotein; Membrane; Reference proteome;
KW Sialic acid; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:17222411"
FT CHAIN 23..162
FT /note="Podoplanin"
FT /id="PRO_0000223875"
FT PEPTIDE 151..162
FT /note="29kDa cytosolic podoplanin intracellular domain"
FT /evidence="ECO:0000269|PubMed:24275092"
FT /id="PRO_0000442187"
FT TOPO_DOM 23..131
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 23..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 85..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 133..137
FT /note="Requires for dimerization and lipid rafts
FT association"
FT /evidence="ECO:0000269|PubMed:21376833"
FT REGION 154..155
FT /note="Requires for interaction with MSN and EZR"
FT /evidence="ECO:0000269|PubMed:17046996"
FT SITE 150..151
FT /note="Cleavage; by gamma-secretase"
FT /evidence="ECO:0000269|PubMed:24275092"
FT CARBOHYD 25
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 32
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:17222411,
FT ECO:0000269|PubMed:25458834"
FT CARBOHYD 55
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 65
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
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 96
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
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 102
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9651190"
FT /id="VSP_051949"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_046799"
FT VAR_SEQ 1
FT /note="M -> MLTPLGKFSTAKFAVRLPRVWEARAPSLSGAPAPTPPAPPPSRSSRL
FT GLWPRCFLIFPQLRILLLGPQESNNSTGTM (in isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15515019,
FT ECO:0000303|PubMed:16303743, ECO:0000303|Ref.9"
FT /id="VSP_035753"
FT VAR_SEQ 101..123
FT /note="ASNVATSHSTEKVDGDTQTTVEK -> MLHILSPMYFFLWGSCFFPLSSS
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9651190"
FT /id="VSP_051950"
FT VAR_SEQ 160..162
FT /note="YSP -> P (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16303743"
FT /id="VSP_035754"
FT VAR_SEQ 160..161
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_046800"
FT VAR_SEQ 162
FT /note="P -> EVNSLHPCDRQMKAIVSRTQIFELIEISDISWVWWLVPVVSAAGQLQ
FT TSLGNIVRPCLKKIISGTMVMFQSSLLGPLECSGSHLESQCFERLRRQEVHLCPGI
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9651190"
FT /id="VSP_051951"
FT VARIANT 105
FT /note="A -> G (in dbSNP:rs2486188)"
FT /id="VAR_028015"
FT VARIANT 147
FT /note="A -> G (in dbSNP:rs2486188)"
FT /evidence="ECO:0000269|PubMed:10393083,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16303743, ECO:0000269|PubMed:9651190,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.9"
FT /id="VAR_028016"
FT MUTAGEN 52
FT /note="T->A: Eliminates induction of platelet aggregation."
FT /evidence="ECO:0000269|PubMed:14522983"
FT MUTAGEN 137
FT /note="Missing: Prevents self-assembly and association to
FT lipid rafts. Reduces the recruitment to invadopodium.
FT Disrupts assembly into adhesion rings. Fails invadopodia-
FT mediated ECM degradation."
FT /evidence="ECO:0000269|PubMed:21376833,
FT ECO:0000269|PubMed:25486435"
FT MUTAGEN 154..159
FT /note="RKMSGR->QNMGSN: Does not affect localization at cell
FT surface protrusions. Does not induce reorganization of the
FT actin cytoskeleton. Increases cell migration collectively.
FT Does not significant change RHOA activation. No effect on
FT interaction with CD44. Impairs interaction with the EZR and
FT MSN. Impairs epithelial to mesenchymal transition. Does not
FT change localization at invadopodium. Fails to assemble into
FT rings. Fails invadopodia-mediated ECM degradation."
FT /evidence="ECO:0000269|PubMed:17046996,
FT ECO:0000269|PubMed:20962267, ECO:0000269|PubMed:25486435"
FT MUTAGEN 154..155
FT /note="RK->QN: Impairs interaction with the EZR and MSN.
FT Impairs epithelial to mesenchymal transition. Does not
FT affect localization at cell surface protrusions. Does not
FT induce reorganization of the actin cytoskeleton. Increases
FT cell migration collectively."
FT /evidence="ECO:0000269|PubMed:17046996"
FT MUTAGEN 159
FT /note="R->N: Highly decreases interaction with the EZR and
FT MSN. Induces an intermediate phenotype between epithelial
FT and mesenchymal. Does not affect localization at cell
FT surface protrusions. Induces reorganization of the actin
FT cytoskeleton oncomitantly with the induced morphological
FT changes. Increases cell migration individually. Increases
FT invasiveness. Enhances RHOA activity. Colocalizes at cell-
FT surface protrusions with RHOA and RAC1."
FT /evidence="ECO:0000269|PubMed:17046996"
FT CONFLICT 57
FT /note="E -> K (in Ref. 8; BAC11557)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 162 AA; 16698 MW; CD96D46FF5BD56A1 CRC64;
MWKVSALLFV LGSASLWVLA EGASTGQPED DTETTGLEGG VAMPGAEDDV VTPGTSEDRY
KSGLTTLVAT SVNSVTGIRI EDLPTSESTV HAQEQSPSAT ASNVATSHST EKVDGDTQTT
VEKDGLSTVT LVGIIVGVLL AIGFIGAIIV VVMRKMSGRY SP
