PDPN_CANLF
ID PDPN_CANLF Reviewed; 169 AA.
AC Q95152;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Podoplanin {ECO:0000250|UniProtKB:Q86YL7};
DE AltName: Full=Mucin-type membrane protein Gp40 {ECO:0000303|PubMed:9337856};
DE Short=Gp40 {ECO:0000303|PubMed:9337856};
DE Flags: Precursor;
GN Name=PDPN; Synonyms=GP40;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=9337856; DOI=10.1042/bj3260099;
RA Zimmer G., Lottspeich F., Maisner A., Klenk H.-D., Herrler G.;
RT "Molecular characterization of gp40, a mucin-type glycoprotein from the
RT apical plasma membrane of Madin-Darby canine kidney cells (type I).";
RL Biochem. J. 326:99-108(1997).
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:0000250|UniProtKB:Q62011}; Single-
CC pass type I membrane protein {ECO:0000255}. Cell projection, filopodium
CC membrane {ECO:0000250|UniProtKB:Q62011}; Single-pass type I membrane
CC protein {ECO:0000255}. Cell projection, lamellipodium membrane
CC {ECO:0000250|UniProtKB:Q62011}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, microvillus membrane
CC {ECO:0000250|UniProtKB:Q62011}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q62011}; 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 (By similarity). Association to the lipid rafts is required for
CC PDPN-induced epithelial to mesenchymal transition (EMT). Colocalizes
CC with CD9 in tetraspanin microdomains. Localized at invadopodium
CC adhesion rings in tumor cell. Association to the lipid rafts is
CC essential for PDPN recruitment to invadopodia and ECM degradation (By
CC similarity). {ECO:0000250|UniProtKB:Q62011,
CC ECO:0000250|UniProtKB:Q86YL7}.
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-59; sialic acid is critical for platelet-
CC aggregating activity and for CLEC1B interaction.
CC {ECO:0000250|UniProtKB:Q86YL7}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:Q64294}.
CC -!- SIMILARITY: Belongs to the podoplanin family. {ECO:0000305}.
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DR EMBL; Z81018; CAB02675.1; -; mRNA.
DR RefSeq; NP_001003220.1; NM_001003220.1.
DR AlphaFoldDB; Q95152; -.
DR STRING; 9615.ENSCAFP00000024086; -.
DR Ensembl; ENSCAFT00030028693; ENSCAFP00030025018; ENSCAFG00030015564.
DR Ensembl; ENSCAFT00040008380; ENSCAFP00040007283; ENSCAFG00040004415.
DR Ensembl; ENSCAFT00040008401; ENSCAFP00040007295; ENSCAFG00040004415.
DR GeneID; 403886; -.
DR KEGG; cfa:403886; -.
DR CTD; 10630; -.
DR eggNOG; ENOG502QRWU; Eukaryota.
DR InParanoid; Q95152; -.
DR OrthoDB; 1303144at2759; -.
DR Reactome; R-CFA-114604; GPVI-mediated activation cascade.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
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: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; ISS:UniProtKB.
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; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0019956; F:chemokine binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0070252; P:actin-mediated cell contraction; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0030324; P:lung development; ISS:UniProtKB.
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:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
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:1901731; P:positive regulation of platelet aggregation; ISS:UniProtKB.
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: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; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
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..169
FT /note="Podoplanin"
FT /id="PRO_0000021351"
FT TOPO_DOM 23..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 37..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 140..144
FT /note="Requires for dimerization and lipid rafts
FT association"
FT /evidence="ECO:0000250|UniProtKB:Q86YL7"
FT REGION 161..162
FT /note="Requires for interaction with MSN and EZR"
FT /evidence="ECO:0000250|UniProtKB:Q86YL7"
FT CARBOHYD 25
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 44
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 47
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q86YL7"
FT CARBOHYD 63
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 72
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 83
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 92
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 106
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 169 AA; 17574 MW; BB2D48FE55C56DBC CRC64;
MWRVPVLLLV LGGAGLRVPA AGASTVRPDD IIPGVEDSVV TPGTEDSVVT PGAEDNVVTD
GATEEPYESG LTPLVTKNTE SVTDLHLEDG PTQESTVHAK EESQSTTTLN VVTSHSREKV
GEDTETTVEK DGLATVTLVG IIVGVLLAIG FIGGIIIVVA RKMSGRYSP
