PDPN_RAT
ID PDPN_RAT Reviewed; 166 AA.
AC Q64294; O08731; O55210;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Podoplanin {ECO:0000303|PubMed:9327748};
DE AltName: Full=E11 antigen epitope {ECO:0000303|PubMed:8833206};
DE AltName: Full=RTI140 {ECO:0000303|PubMed:9761764, ECO:0000303|PubMed:9920397};
DE AltName: Full=T1-alpha {ECO:0000303|PubMed:7851650};
DE Short=T1A {ECO:0000303|PubMed:7851650};
DE AltName: Full=Type I cell 40 kDa protein;
DE Flags: Precursor;
GN Name=Pdpn {ECO:0000312|RGD:61819};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=7851650; DOI=10.1006/dbio.1995.1024;
RA Rishi A.K., Joyce-Brady M., Fisher J., Dobbs L.G., Floros J.,
RA Vanderspek J., Brody J.S., Williams M.C.;
RT "Cloning, characterization, and development expression of a rat lung
RT alveolar type I cell gene in embryonic endodermal and neural derivatives.";
RL Dev. Biol. 167:294-306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Osteosarcoma;
RX PubMed=8833206; DOI=10.1016/8756-3282(95)00457-2;
RA Wetterwald A., Hoffstetter W., Cecchini M.G., Lanske B., Wagner C.,
RA Fleisch H., Atkinson M.;
RT "Characterization and cloning of the E11 antigen, a marker expressed by rat
RT osteoblasts and osteocytes.";
RL Bone 18:125-132(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DOWN-REGULATION IN PAN.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=9327748;
RA Breiteneder-Geleff S., Matsui K., Soleiman A., Meraner P., Poczewski H.,
RA Kalt R., Schaffner G., Kerjaschki D.;
RT "Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells,
RT is down-regulated in puromycin nephrosis.";
RL Am. J. Pathol. 151:1141-1152(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=9761764; DOI=10.1165/ajrcmb.19.4.3121;
RA Vanderbilt J.N., Dobbs L.G.;
RT "Characterization of the gene and promoter for RTI40, a differentiation
RT marker of type I alveolar epithelial cells.";
RL Am. J. Respir. Cell Mol. Biol. 19:662-671(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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]
RP PROTEIN SEQUENCE OF 41-55, GLYCOSYLATION, AND BLOCKAGE OF N-TERMINUS.
RX PubMed=9920397; DOI=10.1016/s0167-4838(98)00231-3;
RA Gonzalez R.F., Dobbs L.G.;
RT "Purification and analysis of RTI40, a type I alveolar epithelial cell
RT apical membrane protein.";
RL Biochim. Biophys. Acta 1429:208-216(1998).
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. Interaction with CD9, on the contrary, attenuates platelet
CC aggregation and pulmonary metastasis induced by PDPN. Mediates effects
CC on cell migration and adhesion through its different partners. Through
CC MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT)
CC leading to ERZ phosphorylation and triggering RHOA activation leading
CC to cell migration increase and invasiveness. Interaction with CD44
CC promotes directional cell migration in epithelial and tumor cells (By
CC similarity). In lymph nodes (LNs), controls fibroblastic reticular
CC cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction
CC of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and
CC 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. In
CC keratinocytes, induces changes in cell morphology showing an elongated
CC shape, numerous membrane protrusions, major reorganization of the actin
CC cytoskeleton, increased motility and decreased cell adhesion. Controls
CC invadopodia stability and maturation leading to efficient degradation
CC of the extracellular matrix (ECM) in tumor cells through modulation of
CC RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and
CC inactivation of CFL1 (By similarity). 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 (By similarity). Does not have any effect on folic acid or
CC amino acid transport (By similarity). {ECO:0000250|UniProtKB:Q62011,
CC ECO:0000250|UniProtKB:Q86YL7}.
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. Interacts with
CC CD9; this interaction is homophilic and attenuates platelet aggregation
CC and pulmonary metastasis induced by PDPN. Interacts with LGALS8; the
CC interaction is glycosylation-dependent; may participate in connection
CC of the lymphatic endothelium to the surrounding extracellular matrix.
CC Interacts with HSPA9. Interacts (via extracellular domain) with CD44;
CC this interaction is required for PDPN-mediated directional migration
CC and regulation of lamellipodia extension/stabilization during cell
CC spreading and migration. Interacts (via cytoplasmic domain) with MSN
CC and EZR; activates RHOA and promotes epithelial-mesenchymal transition.
CC Interacts with CCL21; relocalized PDPN to the basolateral membrane.
CC {ECO:0000250|UniProtKB:Q86YL7}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9327748}; Single-
CC pass type I membrane protein {ECO:0000255}. Cell projection,
CC lamellipodium membrane {ECO:0000269|PubMed:9327748}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell projection, filopodium membrane
CC {ECO:0000269|PubMed:9327748}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, microvillus membrane
CC {ECO:0000269|PubMed:9327748}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:9327748}; 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:9327748). 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:9327748}.
CC -!- TISSUE SPECIFICITY: In adult kidney, expressed on the urinary surface
CC and foot processes of podocytes and in parietal epithelial cells of
CC Bowman's capsule where it is localized to luminal surfaces. In lung,
CC expressed exclusively on luminal surfaces of type I alveolar epithelial
CC cells and pleural mesothelial cells. Not expressed in type II alveolar
CC cells. In bone, expressed in osteocytes and osteoblasts. In spleen,
CC liver, stomach and intestine, expressed in mesoepithelium. Also
CC expressed in thymic epithelial cells, choroid plexus and leptomeninges.
CC {ECO:0000269|PubMed:9327748, ECO:0000269|PubMed:9761764}.
CC -!- DEVELOPMENTAL STAGE: In newborn kidney, not detected at the vesicle
CC stage. First detected in S-shaped bodies. {ECO:0000269|PubMed:9327748}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:Q62011,
CC ECO:0000250|UniProtKB:Q86YL7}.
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:9920397}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:9920397}.
CC -!- MISCELLANEOUS: Down-regulated in puromycin aminonucleoside nephrosis
CC (PAN).
CC -!- SIMILARITY: Belongs to the podoplanin family. {ECO:0000305}.
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DR EMBL; U07797; AAA92789.1; -; mRNA.
DR EMBL; U32115; AAA74431.1; -; mRNA.
DR EMBL; U96449; AAB86438.1; -; mRNA.
DR EMBL; U92440; AAB93880.1; -; Genomic_DNA.
DR EMBL; U92081; AAB93880.1; JOINED; Genomic_DNA.
DR EMBL; BC072492; AAH72492.1; -; mRNA.
DR RefSeq; NP_062231.1; NM_019358.1.
DR AlphaFoldDB; Q64294; -.
DR SMR; Q64294; -.
DR CORUM; Q64294; -.
DR STRING; 10116.ENSRNOP00000020316; -.
DR GlyGen; Q64294; 18 sites.
DR PaxDb; Q64294; -.
DR PRIDE; Q64294; -.
DR GeneID; 54320; -.
DR KEGG; rno:54320; -.
DR UCSC; RGD:61819; rat.
DR CTD; 10630; -.
DR RGD; 61819; Pdpn.
DR eggNOG; ENOG502QRWU; Eukaryota.
DR InParanoid; Q64294; -.
DR OrthoDB; 1303144at2759; -.
DR PhylomeDB; Q64294; -.
DR TreeFam; TF337068; -.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR PRO; PR:Q64294; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0042995; C:cell projection; ISS:UniProtKB.
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; ISO:RGD.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0031527; C:filopodium membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS: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; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISO:RGD.
DR GO; GO:0019956; F:chemokine binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0070252; P:actin-mediated cell contraction; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IDA:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
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:0007399; P:nervous system development; IEP:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA: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; IMP:RGD.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; ISS: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; IEP:RGD.
DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0035239; P:tube morphogenesis; IDA:MGI.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
PE 1: Evidence at protein level;
KW 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..166
FT /note="Podoplanin"
FT /id="PRO_0000021353"
FT TOPO_DOM 23..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 54..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..141
FT /note="Requires for dimerization and lipid rafts
FT association"
FT /evidence="ECO:0000250|UniProtKB:Q86YL7"
FT REGION 158..159
FT /note="Requires for interaction with MSN and EZR"
FT /evidence="ECO:0000250|UniProtKB:Q86YL7"
FT COMPBIAS 81..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 34
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 55
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 62
FT /note="O-linked (GalNAc...) serine"
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 80
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 83
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 94
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
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 105
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CONFLICT 112
FT /note="P -> S (in Ref. 3; AAB86438 and 5; AAH72492)"
FT /evidence="ECO:0000305"
FT CONFLICT 135..137
FT /note="LVG -> WSA (in Ref. 4; AAB93880)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 166 AA; 17579 MW; B97C58292B664468 CRC64;
MWTAPVLLWV LGSVWFWDSA QGGAIGALED DLVTPGPGDD MVNPGLEDRI ETTDTTGELD
KSTAKAPLVP TQPPIEELPT SGTSDHDHKE HESTTTVKAV TSHSTDKKTT HPNRDNAGGE
TQTTDKKDGL AVVTLVGIII GVLLAIGFIG GIIIVVMRKI SGRFSP
