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Protein

Podoplanin

Gene

Pdpn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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 Expressed in 285 organ(s), highest expression level in camera-type eye
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

3D structure databases

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A8Y5F6A8Y5F6_MOUSE
Podoplanin
Pdpn
159Annotation score:

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

Cross-referencesi

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

3D structure databases

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

Protein-protein interaction databases

IntActiQ62011, 1 interactor
STRINGi10090.ENSMUSP00000030317

PTM databases

iPTMnetiQ62011
PhosphoSitePlusiQ62011

Proteomic databases

MaxQBiQ62011
PaxDbiQ62011
PRIDEiQ62011

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10630
MGIiMGI:103098 Pdpn

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-114604 GPVI-mediated activation cascade

Miscellaneous databases

ChiTaRSiPdpn mouse
PROiPR:Q62011
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028583 Expressed in 285 organ(s), highest expression level in camera-type eye
CleanExiMM_PDPN
ExpressionAtlasiQ62011 baseline and differential
GenevisibleiQ62011 MM

Family and domain databases

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

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: September 12, 2018
This is version 138 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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