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Protein

Podoplanin

Gene

Pdpn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 to 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).By similarity8 Publications

GO - Molecular functioni

GO - Biological processi

  • actin-mediated cell contraction Source: UniProtKB
  • cell adhesion Source: MGI
  • cell-cell adhesion Source: MGI
  • cell morphogenesis Source: UniProtKB
  • cell proliferation Source: MGI
  • invadopodium organization Source: UniProtKB
  • lung alveolus development Source: MGI
  • lung development Source: MGI
  • lymphangiogenesis Source: MGI
  • lymphatic endothelial cell fate commitment Source: UniProtKB
  • lymph node development Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cellular component movement Source: UniProtKB
  • positive regulation of epithelial to mesenchymal transition Source: UniProtKB
  • positive regulation of extracellular matrix disassembly Source: UniProtKB
  • positive regulation of platelet aggregation Source: UniProtKB
  • prostaglandin metabolic process Source: MGI
  • regulation of cell adhesion Source: UniProtKB
  • regulation of cell shape Source: UniProtKB-KW
  • regulation of G1/S transition of mitotic cell cycle Source: MGI
  • regulation of lamellipodium morphogenesis Source: UniProtKB
  • regulation of myofibroblast contraction Source: UniProtKB
  • regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • Rho protein signal transduction Source: UniProtKB
  • signal transduction Source: MGI
  • tube morphogenesis Source: MGI
  • visceral serous pericardium development Source: DFLAT
  • wound healing, spreading of cells Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein
Biological processCell shape
LigandSialic acid

Enzyme and pathway databases

ReactomeiR-MMU-114604. GPVI-mediated activation cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
PodoplaninBy similarity
Alternative name(s):
Glycoprotein 381 Publication
Short name:
Gp381 Publication
OTS-81 Publication
PA2.26 antigen1 Publication
Transmembrane glycoprotein E111 Publication
Short name:
E111 Publication
Gene namesi
Name:PdpnImported
Synonyms:Gp381 Publication, Ots8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:103098. Pdpn.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 141ExtracellularSequence analysisAdd BLAST119
Transmembranei142 – 162HelicalSequence analysisAdd BLAST21
Topological domaini163 – 172Cytoplasmic10

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice die at birth of respiratory failure due to a low number of attenuated type I cells, narrow and irregular air spaces, and defective formation of alveolar saccules (PubMed:12654292). Knockout Pdpn mice neonates are smaller, and approximately 55% died during the first postnatal week. However, approximately 20% survived, had normal weights and life spans, and are fertile (PubMed:20110424).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi34T → A: Eliminates platelet aggregation activity. 1 Publication1
Mutagenesisi167S → A: 50% decrease of cell growth; when associated with A-171. 50% increase of cell migration; when associated with A-171. 1 Publication1
Mutagenesisi167S → D: Does not significantly increase cell motility; when associated with D-171. Does not significantly decrease cell growth; when associated with A-171. 1 Publication1
Mutagenesisi171S → A: 50% decrease of cell growth; when associated with A-167. 50% increase of cell migration; when associated with A-167. 1 Publication1
Mutagenesisi171S → D: Does not significantly increase cell motility; when associated with D-171. Does not significantly decrease cell growth; when associated with A-171. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22By similarityAdd BLAST22
ChainiPRO_000002135223 – 172PodoplaninAdd BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi51O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi52O-linked (GalNAc...) threonineBy similarity1
Glycosylationi53O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi56O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi60N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi63O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi71O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi77O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi85O-linked (GalNAc...) serineSequence analysis1
Glycosylationi86O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi87O-linked (GalNAc...) serineSequence analysis1
Glycosylationi89O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi90O-linked (GalNAc...) serineSequence analysis1
Glycosylationi100O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi101O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi102O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi107O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi115O-linked (GalNAc...) threonineSequence analysis1

Post-translational modificationi

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 (By similarity).By similarity2 Publications
Phosphorylated by PKA; decreases cell migration.1 Publication
The N-terminus is blocked.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ62011.
PaxDbiQ62011.
PRIDEiQ62011.

PTM databases

iPTMnetiQ62011.
PhosphoSitePlusiQ62011.

Expressioni

Tissue specificityi

Detected at high levels in lung and brain, at lower levels in kidney, stomach, liver, spleen and esophagus, and not detected in skin and small intestine. Expressed in epithelial cells of choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells and in endothelia of lymphatic vessels. Also expressed in stromal cells of peripheral lymphoid tissue and thymic epithelial cells. Detected in carcinoma cell lines and cultured fibroblasts. Expressed at higher levels in colon carcinomas than in normal colon tissue.3 Publications

Developmental stagei

At E12.5 and E13.5 is expressed in the endothelial cells of forming lymph sacs.1 Publication

Inductioni

Down-regulated by treatment with puromycin aminonucleoside (PubMed:12032185). Up-regulated during progression to highly aggressive tumors and during epithelial-mesenchymal transition (EMT) (PubMed:20962267).2 Publications

Gene expression databases

BgeeiENSMUSG00000028583.
CleanExiMM_PDPN.
ExpressionAtlasiQ62011. baseline and differential.
GenevisibleiQ62011. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with CLEC1B; the interaction is independent of CLEC1B glycosylation and activates CLEC1B; the interaction is dependent of sialic acid on O-glycans (PubMed:17616532). Interacts with CD9; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Interacts with LGALS8; the interaction is glycosylation-dependent; may participate to connection of the lymphatic endothelium to the surrounding extracellular matrix. Interacts with HSPA9. Interacts (via extracellular domain) with CD44; this interaction is required for PDPN-mediated directional migration and regulation of lamellipodia extension/stabilization during cell spreading and migration. Interacts (via cytoplasmic domain) with MSN and EZR; activates RHOA and promotes epithelial-mesenchymal transition. Interacts with CCL21; relocalized PDPN to the basolateral membrane (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ62011. 1 interactor.
STRINGi10090.ENSMUSP00000030317.

Structurei

Secondary structure

1172
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi81 – 83Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3IETX-ray2.20Q/X76-84[»]
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni143 – 147Requires for dimerization and lipidd rafts associationBy similarity5
Regioni164 – 165Requires for interaction with MSN and EZRBy similarity2

Domaini

The cytoplasmic domain controls FRC elongation but is dispensable for contraction (PubMed:25347465). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (By similarity).By similarity1 Publication

Sequence similaritiesi

Belongs to the podoplanin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J49G. Eukaryota.
ENOG41116TP. LUCA.
GeneTreeiENSGT00390000000013.
HOGENOMiHOG000231122.
HOVERGENiHBG080131.
InParanoidiQ62011.
KOiK16778.
OMAiETTGMEG.
OrthoDBiEOG091G0ZYJ.
PhylomeDBiQ62011.
TreeFamiTF337068.

Family and domain databases

InterProiView protein in InterPro
IPR008783. Podoplanin.
PfamiView protein in Pfam
PF05808. Podoplanin. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62011-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWTVPVLFWV LGSVWFWDSA QGGTIGVNED DIVTPGTGDG MVPPGIEDKI
60 70 80 90 100
TTTGATGGLN ESTGKAPLVP TQRERGTKPP LEELSTSATS DHDHREHEST
110 120 130 140 150
TTVKVVTSHS VDKKTSHPNR DNAGDETQTT DKKDGLPVVT LVGIIVGVLL
160 170
AIGFVGGIFI VVMKKISGRF SP
Length:172
Mass (Da):18,233
Last modified:November 1, 1997 - v2
Checksum:iC035ED251918CE6F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29 – 31EDD → KNN in AAA37724 (PubMed:1402691).Curated3
Sequence conflicti38 – 39GD → EN in AAA37724 (PubMed:1402691).Curated2
Sequence conflicti170 – 172FSP → SRPKELNRTGCSPNTSENKR ASNLPCSPSSSCGGR in AAA39866 (PubMed:2088477).Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M73748 mRNA. Translation: AAA39866.1.
M96645 mRNA. Translation: AAA37724.1.
AJ250246 mRNA. Translation: CAB58997.1.
AJ297944 mRNA. Translation: CAC16152.1.
AY115493 Genomic DNA. Translation: AAM66761.1.
AK158855 mRNA. Translation: BAE34695.1.
AL611982 Genomic DNA. Translation: CAM21724.1.
BC026551 mRNA. Translation: AAH26551.1.
CCDSiCCDS38943.1.
PIRiA54560.
RefSeqiNP_001277751.1. NM_001290822.1.
NP_034459.2. NM_010329.3.
UniGeneiMm.2976.

Genome annotation databases

EnsembliENSMUST00000030317; ENSMUSP00000030317; ENSMUSG00000028583.
ENSMUST00000181754; ENSMUSP00000137969; ENSMUSG00000096951.
GeneIDi14726.
KEGGimmu:14726.
UCSCiuc008vqa.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiPDPN_MOUSE
AccessioniPrimary (citable) accession number: Q62011
Secondary accession number(s): A2A8J3, Q546R8, Q61612
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 22, 2017
This is version 135 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families