Browse PDPN

Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Podoplanin: Membrane Single-pass type I membrane protein Cell projection, lamellipodium membrane Single-pass type I membrane protein Cell projection, filopodium membrane Single-pass type I membrane protein Cell projection, microvillus membrane Single-pass type I membrane protein Cell projection, ruffle membrane Single-pass type I membrane protein Membrane raft Apical cell membrane Basolateral cell membrane Cell projection, invadopodium Note=Localized to actin-rich microvilli and plasma membrane projections such as filopodia, lamellipodia and ruffles (By similarity). Association to the lipid rafts is required for PDPN-induced epithelial to mesenchymal transition (EMT) (PubMed:21376833). Colocalizes with CD9 in tetraspanin microdomains (PubMed:18541721). Localized at invadopodium adhesion rings in tumor cell. Association to the lipid rafts is essential for PDPN recruitment to invadopodia and ECM degradation (PubMed:25486435). ; SUBCELLULAR LOCATION: 29kDa cytosolic podoplanin intracellular domain: Cytoplasm, cytosol
Domain PF05808 Podoplanin
Function

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).

> Gene Ontology
 
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
GO:0001945 lymph vessel development
GO:0001946 lymphangiogenesis
GO:0006631 fatty acid metabolic process
GO:0006690 icosanoid metabolic process
GO:0006692 prostanoid metabolic process
GO:0006693 prostaglandin metabolic process
GO:0007346 regulation of mitotic cell cycle
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008360 regulation of cell shape
GO:0022604 regulation of cell morphogenesis
GO:0030168 platelet activation
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0033559 unsaturated fatty acid metabolic process
GO:0036303 lymph vessel morphogenesis
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0048286 lung alveolus development
GO:0050817 coagulation
GO:0050878 regulation of body fluid levels
GO:0051272 positive regulation of cellular component movement
GO:0060541 respiratory system development
GO:1901987 regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1902806 regulation of cell cycle G1/S phase transition
GO:2000045 regulation of G1/S transition of mitotic cell cycle
Molecular Function -
Cellular Component GO:0001726 ruffle
GO:0005902 microvillus
GO:0009897 external side of plasma membrane
GO:0030027 lamellipodium
GO:0030175 filopodium
GO:0031252 cell leading edge
GO:0031253 cell projection membrane
GO:0031256 leading edge membrane
GO:0031258 lamellipodium membrane
GO:0031527 filopodium membrane
GO:0031528 microvillus membrane
GO:0032587 ruffle membrane
GO:0098552 side of membrane
GO:0098858 actin-based cell projection
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-114604: GPVI-mediated activation cascade
R-HSA-109582: Hemostasis
R-HSA-139943: PLC-mediated hydrolysis of PIP2
R-HSA-76002: Platelet activation, signaling and aggregation
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PDPN and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between PDPN and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23690472Pleural Malignant MesotheliomaImmunotherapy targetPodoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM.
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PDPN in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PDPN in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.6540.302
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.1410.445
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2820.781
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.4810.274
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.1860.442
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4080.829
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2180.732
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0530.963
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2480.856
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9290.338
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.790.187
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1430.496
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PDPN in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDPN. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDPN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDPN.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDPN. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PDPN expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PDPN and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPDPN
Namepodoplanin
Aliases T1A-2; Gp38; aggrus; PA2.26; lung type I cell membrane associated glycoprotein; GP36; HT1A-1; OTS8; T1A; T1A ......
Chromosomal Location1p36.21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PDPN collected from DrugBank database.
> Drugs from DrugBank database
 

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