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FLASH GENE
Symbol PODXL contributors: mct/shn - updated : 30-03-2020
HGNC name podocalyxin-like
HGNC id 9171
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • single membrane-spanning region
  • extracellular multiple potential sites for N and O-linked glycosylation and four cysteines
  • share an identical C-terminal PDZ-binding motif (DTHL) with PODXL2 (
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Podxl, Mus musculus
    ortholog to PODXL, Pan troglodytes
    ortholog to podxl, Danio rerio
    ortholog to Podxl, Rattus norvegicus
    intraspecies paralog to CD34
    Homologene
    FAMILY
  • sialomucin protein family
  • CD 34 family
  • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleolus
    text
  • intact PODXL is released to the extracellular space as a cargo of microvesicles and also as a soluble cleaved fragment of ectodomain
  • basic FUNCTION
  • functioning as an antiadhesin that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion
  • extensively O&
  • 8208;linked glycosylated glycoprotein
  • enhances the adherence of cells to immobilized ligands and to vascular endothelial cells through a mechanism dependent on the activity of integrins
  • is essential for maintaining the elaborate structure of kidney podocytes (
  • potentially playing a role in cell migration and cell-cell recognition during brain development
  • in pluripotent stem cells and in cancer disease, may function in part to regulate and maintain the cell surface expression of SLC2A3
  • may function in part to regulate and maintain the cell surface expression of the glucose-3-transporter
  • renal polysialylated-containing protein that has been reported to function as an anti-adhesin in kidney podocytes
  • second highly sialylated neural adhesion protein, playing multiple roles in neural development
  • integrity of the PODXL ectodomain is essential for enhancing cell adhesion but not migration, while the integrity of the cytoplasmic domain is required for both adhesion and migration
  • in endothelial cells, podocalyxin plays a previously unrecognized role in maintaining vascular integrity, likely through orchestrating interactions with extracellular matrix components and basement membrane
  • new function of PODXL expressed on tumor cells as an immunomodulatory molecule, which may represent a mechanism to evade the immune response
  • potential role of PODXL in neural development
  • having roles in renal podocyte diaphragm slit development
  • is a novel keratan sulfate (KS) proteoglycan in undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs)
  • specific functions for PODXL in maintaining endothelial barrier function
  • has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers
  • PODXL expression by CNS tissue vascular endothelial cells (vECs) is essential for blood-brain barrier (BBB) maintenance under inflammatory conditions
  • role for PODXL in mature B-cell non-Hodgkin lymphoma (B-NHL) cell proliferation, survival, migration, drug resistance, and metabolic reprogramming
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • integral constituent of the glomerular epithelial cell glycocalyx
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79
  • linked to ezrin and the actin cytoskeleton via Na(+)/H(+)-exchanger regulatory factor, 2 NHERF2
  • actin filaments in podocytes mediated by CTTN and alteration of this interaction may play a role in the process of morphological change of podocytes
  • glucose-3-transporter (SLC2A3) and the cell-adhesion protein PODXL
  • novel molecular connection between PODXL and ANXA2: both exert pro-survival effects in neural stem/progenitor cells (NSPs), and PODXL positively regulates ANXA2 expression through the MAPK pathway
  • novel roles for PODXL as an important modulator of neutrophil and monocyte formation and of RAP1A activation during stress hematopoiesis
  • PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein EZR
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ARJPK1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer cells might promote metastasis by disrupting cell adhesion, particularly during apical membrane expansion
    constitutional germinal mutation     loss of function
    lead to adult-onset focal segmental glomerulosclerosis (FSGS)
    constitutional     --over  
    significantly increased in preeclampsia at disease presentation
    tumoral     --over  
    in prostate cancer
    constitutional germinal mutation     loss of function
    patient presenting with congenital nephrotic syndrome, omphalocele and microcoria
    Susceptibility to prostate cancer with tumor aggressiveness
    Variant & Polymorphism other variant 340A increasing the risk of prostate cancer with tumor aggressiveness
    Candidate gene
    Marker
  • useful prognostic marker for astrocytic tumors
  • EZR, CLIC5 and PODXL could be likely biological markers to predict the prognosis of hepatocellular carcinoma (HCC) and these proteins participate in migration and invasion processes
  • putative immunohistochemical marker of prostate cancer that may contribute to stratification of patients for optimal treatment
  • Therapy target
    ANIMAL & CELL MODELS
  • transient knockdown of PODXL or the expression of PODXL lacking the cytosolic carboxyterminal domain (PODXL-Delta(451)) inhibited cell adherence
  • siRNA podocalyxin-knockdown experiments show decreased expression levels of the glucose-3-transporter