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Protein

Podoplanin

Gene

PDPN

Organism
Homo sapiens (Human)
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:17616532, PubMed:18215137, PubMed:17222411). Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN (PubMed:18541721). 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 (PubMed:17046996, PubMed:21376833). Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (PubMed:20962267). 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 (By similarity). Through binding with LGALS8 may participate to connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462). 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:15515019). 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 (PubMed:25486435). Required for normal lung cell proliferation and alveolus formation at birth (By similarity). Does not function as a water channel or as a regulator of aquaporin-type water channels (PubMed:9651190). Does not have any effect on folic acid or amino acid transport (By similarity).By similarity13 Publications

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • chemokine binding Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • actin-mediated cell contraction Source: UniProtKB
  • cell-cell adhesion Source: Ensembl
  • cell morphogenesis Source: UniProtKB
  • cell proliferation Source: Ensembl
  • invadopodium organization Source: UniProtKB
  • lung alveolus development Source: Ensembl
  • lung development Source: UniProtKB
  • lymphangiogenesis Source: UniProtKB
  • 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
  • platelet activation 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: Ensembl
  • regulation of cell shape Source: UniProtKB-KW
  • regulation of G1/S transition of mitotic cell cycle Source: Ensembl
  • 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
  • wound healing, spreading of cells Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein
Biological processCell shape
LigandSialic acid

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Podoplanin1 Publication
Alternative name(s):
Aggrus1 Publication
Glycoprotein 36
Short name:
Gp361 Publication
PA2.26 antigen1 Publication
T1-alphaBy similarity
Short name:
T1ABy similarity
Cleaved into the following chain:
29kDa cytosolic podoplanin intracellular domain1 Publication
Short name:
PICD1 Publication
Gene namesi
Name:PDPNImported
Synonyms:GP361 Publication
ORF Names:PSEC0003, PSEC0025
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000162493.16.
HGNCiHGNC:29602. 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 – 131ExtracellularSequence analysisAdd BLAST109
Transmembranei132 – 152HelicalSequence analysisAdd BLAST21
Topological domaini153 – 162CytoplasmicSequence analysis10

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52T → A: Eliminates induction of platelet aggregation. 1 Publication1
Mutagenesisi137Missing : Prevents self-assembly and association to lipid rafts. Reduces the recruitment to invadopodium. Disrupts assembly into adhesion rings. Fails invadopodia-mediated ECM degradation. 2 Publications1
Mutagenesisi154 – 159RKMSGR → QNMGSN: Does not affect localization at cell surface protrusions. Does not induce reorganization of the actin cytoskeleton. Increases cell migration collectively. Does not significant change RHOA activation. No effect on interaction with CD44. Impairs interaction with the EZR and MSN. Impairs epithelial to mesenchymal transition. Does not change localization at invadopodium. Fails to assemble into rings. Fails invadopodia-mediated ECM degradation. 3 Publications6
Mutagenesisi154 – 155RK → QN: Impairs interaction with the EZR and MSN. Impairs epithelial to mesenchymal transition. Does not affect localization at cell surface protrusions. Does not induce reorganization of the actin cytoskeleton. Increases cell migration collectively. 1 Publication2
Mutagenesisi159R → N: Highly decreases interaction with the EZR and MSN. Induces an intermediate phenotype between epithelial and mesenchymal. Does not affect localization at cell surface protrusions. Induces reorganization of the actin cytoskeleton oncomitantly with the induced morphological changes. Increases cell migration individually. Increases invasiveness. Enhances RHOA activity. Colocalizes at cell-surface protrusions with RHOA and RAC1. 1 Publication1

Organism-specific databases

DisGeNETi10630.
OpenTargetsiENSG00000162493.
PharmGKBiPA142671187.

Polymorphism and mutation databases

BioMutaiPDPN.
DMDMi215274223.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000022387523 – 162PodoplaninAdd BLAST140
PeptideiPRO_0000442187151 – 16229kDa cytosolic podoplanin intracellular domain1 PublicationAdd BLAST12

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi25O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi32O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi34O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi35O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi52O-linked (GalNAc...) threonine2 Publications1
Glycosylationi55O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi65O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi66O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi76O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi85O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi86O-linked (GalNAc...) serineSequence analysis1
Glycosylationi88O-linked (GalNAc...) serineSequence analysis1
Glycosylationi89O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi96O-linked (GalNAc...) serineSequence analysis1
Glycosylationi98O-linked (GalNAc...) serineSequence analysis1
Glycosylationi100O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi102O-linked (GalNAc...) serineSequence analysis1
Glycosylationi106O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi107O-linked (GalNAc...) serineSequence analysis1
Glycosylationi109O-linked (GalNAc...) serineSequence analysis1
Glycosylationi110O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi117O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi119O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi120O-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 (PubMed:17222411, PubMed:25458834).5 Publications
The N-terminus is blocked.By similarity
Cleaved by a metalloprotease within its extracellular (EC) domain, generating a membrane-bound C-terminal fragment (PCTF33) and an extracellular fragment. The resulting membrane-bound C-terminal fragment (PCTF33) is further processed between Val-150 and Val-151 by PSEN1/gamma-secretase generating the intracellular domain of podoplanin (PICD).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei150 – 151Cleavage; by gamma-secretase1 Publication2

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ86YL7.
PeptideAtlasiQ86YL7.
PRIDEiQ86YL7.

PTM databases

PhosphoSitePlusiQ86YL7.

Expressioni

Tissue specificityi

Highly expressed in placenta, lung, skeletal muscle and brain. Weakly expressed in brain, kidney and liver. In placenta, expressed on the apical plasma membrane of endothelium. In lung, expressed in alveolar epithelium. Up-regulated in colorectal tumors and expressed in 25% of early oral squamous cell carcinomas.3 Publications

Gene expression databases

BgeeiENSG00000162493.
CleanExiHS_PDPN.
ExpressionAtlasiQ86YL7. baseline and differential.
GenevisibleiQ86YL7. HS.

Organism-specific databases

HPAiCAB008376.
HPA007534.
HPA073453.

Interactioni

Subunit structurei

Homodimer (PubMed:21376833). Interacts with CLEC1B; the interaction is independent of CLEC1B glycosylation and activates CLEC1B; the interaction is dependent of sialic acid on O-glycans (PubMed:18215137, PubMed:17616532, PubMed:25458834). Interacts with CD9; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN (PubMed:18541721). Interacts with LGALS8; the interaction is glycosylation-dependent; may participate to connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462). Interacts with HSPA9 (PubMed:23541579). 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 (PubMed:20962267). Interacts (via cytoplasmic domain) with MSN and EZR; activates RHOA and promotes epithelial-mesenchymal transition (PubMed:17046996). Interacts with CCL21; relocalized PDPN to the basolateral membrane (PubMed:14978162).10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CLEC1BQ9P126-12EBI-723160,EBI-16130833

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • chemokine binding Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115874. 4 interactors.
DIPiDIP-61333N.
IntActiQ86YL7. 2 interactors.
MINTiMINT-1411422.
STRINGi9606.ENSP00000294489.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3WSRX-ray1.91C/D38-54[»]
4YO0X-ray1.56E/F38-51[»]
ProteinModelPortaliQ86YL7.
SMRiQ86YL7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 137Requires for dimerization and lipid rafts association1 Publication5
Regioni154 – 155Requires for interaction with MSN and EZR1 Publication2

Domaini

The cytoplasmic domain controls FRC elongation but is dispensable for contraction (By similarity). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (PubMed:25486435).By similarity1 Publication

Sequence similaritiesi

Belongs to the podoplanin family.Sequence analysis

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J49G. Eukaryota.
ENOG41116TP. LUCA.
GeneTreeiENSGT00390000000013.
HOVERGENiHBG080131.
InParanoidiQ86YL7.
KOiK16778.
OrthoDBiEOG091G0ZYJ.
PhylomeDBiQ86YL7.
TreeFamiTF337068.

Family and domain databases

Gene3Di1.20.5.100. 1 hit.
InterProiView protein in InterPro
IPR021157. Cyt_c1_TM_anchor_C.
IPR008783. Podoplanin.
PfamiView protein in Pfam
PF05808. Podoplanin. 1 hit.

Sequences (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q86YL7-1) [UniParc]FASTAAdd to basket
Also known as: hT1alpha-21 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWKVSALLFV LGSASLWVLA EGASTGQPED DTETTGLEGG VAMPGAEDDV
60 70 80 90 100
VTPGTSEDRY KSGLTTLVAT SVNSVTGIRI EDLPTSESTV HAQEQSPSAT
110 120 130 140 150
ASNVATSHST EKVDGDTQTT VEKDGLSTVT LVGIIVGVLL AIGFIGAIIV
160
VVMRKMSGRY SP
Length:162
Mass (Da):16,698
Last modified:November 25, 2008 - v3
Checksum:iCD96D46FF5BD56A1
GO
Isoform 21 Publication (identifier: Q86YL7-2) [UniParc]FASTAAdd to basket
Also known as: hT1alpha-11 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.
     101-123: ASNVATSHSTEKVDGDTQTTVEK → MLHILSPMYFFLWGSCFFPLSSS
     162-162: P → EVNSLHPCDR...RQEVHLCPGI

Show »
Length:164
Mass (Da):18,173
Checksum:i009F6A03EE83F72A
GO
Isoform 3 (identifier: Q86YL7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLTPLGKFST...QESNNSTGTM

Show »
Length:238
Mass (Da):24,902
Checksum:iF6A351B5583198FC
GO
Isoform 4 (identifier: Q86YL7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLTPLGKFST...QESNNSTGTM
     160-162: YSP → P

Show »
Length:236
Mass (Da):24,652
Checksum:i5D85583198FCE2C3
GO
Isoform 5 (identifier: Q86YL7-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.
     160-161: Missing.

Note: No experimental confirmation available.
Show »
Length:118
Mass (Da):12,171
Checksum:i7EB21A53B3CAA7E5
GO
Isoform 6 (identifier: Q86YL7-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.

Note: No experimental confirmation available.
Show »
Length:120
Mass (Da):12,421
Checksum:i9DE0D2821A53B3CA
GO

Sequence cautioni

The sequence AAM73655 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAO22143 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC11550 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC11557 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG35495 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57E → K in BAC11557 (PubMed:16303743).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028015105A → G. Corresponds to variant dbSNP:rs2486188Ensembl.1
Natural variantiVAR_028016147A → G7 PublicationsCorresponds to variant dbSNP:rs2486188Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0519491 – 100Missing in isoform 2. 1 PublicationAdd BLAST100
Alternative sequenceiVSP_0467991 – 42Missing in isoform 5 and isoform 6. CuratedAdd BLAST42
Alternative sequenceiVSP_0357531M → MLTPLGKFSTAKFAVRLPRV WEARAPSLSGAPAPTPPAPP PSRSSRLGLWPRCFLIFPQL RILLLGPQESNNSTGTM in isoform 3 and isoform 4. 5 Publications1
Alternative sequenceiVSP_051950101 – 123ASNVA…TTVEK → MLHILSPMYFFLWGSCFFPL SSS in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_035754160 – 162YSP → P in isoform 4. 1 Publication3
Alternative sequenceiVSP_046800160 – 161Missing in isoform 5. Curated2
Alternative sequenceiVSP_051951162P → EVNSLHPCDRQMKAIVSRTQ IFELIEISDISWVWWLVPVV SAAGQLQTSLGNIVRPCLKK IISGTMVMFQSSLLGPLECS GSHLESQCFERLRRQEVHLC PGI in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030427 mRNA. Translation: AAD01899.1.
AF030428 mRNA. Translation: AAD01900.1.
AJ225022 mRNA. Translation: CAA12352.1.
AB127958 mRNA. Translation: BAD04046.1.
AL359771, AL354712 Genomic DNA. Translation: CAI17983.2.
AL359771, AL354712 Genomic DNA. Translation: CAI17984.2.
BC014668 mRNA. Translation: AAH14668.2.
BC022812 mRNA. Translation: AAH22812.2.
AY194238 mRNA. Translation: AAO22143.1. Different initiation.
AK312607 mRNA. Translation: BAG35495.1. Different initiation.
AK075327 mRNA. Translation: BAC11550.1. Different initiation.
AK075345 mRNA. Translation: BAC11557.1. Different initiation.
AF390106 mRNA. Translation: AAM73655.1. Different initiation.
CCDSiCCDS30602.1. [Q86YL7-3]
CCDS41266.1. [Q86YL7-4]
CCDS44060.1. [Q86YL7-6]
CCDS53270.1. [Q86YL7-5]
RefSeqiNP_001006625.1. NM_001006624.1. [Q86YL7-6]
NP_001006626.1. NM_001006625.1. [Q86YL7-5]
NP_006465.3. NM_006474.4. [Q86YL7-3]
NP_938203.2. NM_198389.2. [Q86YL7-4]
XP_006710358.1. XM_006710295.1. [Q86YL7-6]
UniGeneiHs.468675.

Genome annotation databases

EnsembliENST00000294489; ENSP00000294489; ENSG00000162493. [Q86YL7-3]
ENST00000376057; ENSP00000365225; ENSG00000162493. [Q86YL7-4]
ENST00000376061; ENSP00000365229; ENSG00000162493. [Q86YL7-6]
ENST00000475043; ENSP00000426063; ENSG00000162493. [Q86YL7-5]
ENST00000487038; ENSP00000427537; ENSG00000162493. [Q86YL7-6]
ENST00000513143; ENSP00000425304; ENSG00000162493. [Q86YL7-6]
ENST00000617617; ENSP00000479591; ENSG00000162493. [Q86YL7-3]
ENST00000621990; ENSP00000478125; ENSG00000162493. [Q86YL7-1]
GeneIDi10630.
KEGGihsa:10630.
UCSCiuc001avc.4. human. [Q86YL7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPDPN_HUMAN
AccessioniPrimary (citable) accession number: Q86YL7
Secondary accession number(s): A9Z1Y2
, B2R6J8, E9PB68, F6QWX5, O60836, O95128, Q7L375, Q8NBQ8, Q8NBR3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: November 25, 2008
Last modified: November 22, 2017
This is version 124 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families