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FLASH GENE
Symbol PECAM1 contributors: mct/pgu - updated : 29-12-2015
HGNC name platelet/endothelial cell adhesion molecule
HGNC id 8823
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 27 AA signal peptide
  • 574 AA extracellular domain
  • six Ig extracellular domains and a long cytoplasmic tail 118 AA
  • two immunoreceptor tyrosine based inhibitory motifs (ITIM)
  • cytoplasmic domain involved in mediating PECAM1-catenin family member interactions
  • conjugated GlycoP , PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors
  • CATEGORY adhesion , antigen
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction
    text
  • a major constituent of the endothelial intercellular cell junction
  • expressed on the surface of platelets and leukocytes, and at the intracellular junctions of confluent endothelial cell monolayers
  • basic FUNCTION
  • target glycoprotein in drug induced immune thrombocytopenia
  • potent suppressor of Bax-mediated apoptosis, inhibiting apoptosis in naturally occurring vascular cells subjected to apoptotic stimuli
  • involved in a receptor mediated signal-transduction pathway regulating capacitation-associated tyrosine phosphorylation in spermatozoa
  • plays an important role in endothelial-leukocyte and endothelial-endothelial cell-cell interactions
  • functions as a suppressor of mitochondria-dependent apoptosis, its C-terminus may have a role in the cytoprotective signaling
  • involved in a number of processes relevant to growth and the spread of primary tumors, including angiogenesis, vascular permeability, and leukocyte trafficking out of the circulation
  • is involved in monocyte-triggered downregulation of platelet reactivity
  • may play a role in the development of ischemic stroke
  • pro-atherogenic, is invloved in sensing rapid changes in fluid shear stress
  • inhibits platelet response to collagen, negatively regulates multiple platelet signaling pathways
  • CDH5 and PECAM1 enhance acute lymphoblastic leukemia migration across brain microvascular endothelial cell monolayers
  • CD99 and CD99L2 act independently of PECAM1 in leukocyte extravasation and cooperate in an independent way to help neutrophils overcome the endothelial basement membrane
  • acts through vascular endothelial cell to regulate metastasis in a novel way, by specifically controlling proliferation, not angiogenesis, in advanced tumor metastases
  • Ig-like molecule expressed by leukocytes and endothelial cells with an established role in the regulation of leukocyte trafficking
  • functions as a nonredundant comodulator of T-cell responses, which specializes in sizing the ensuing immune response by setting the threshold for T-cell activation and tolerance, while preventing memory T-cell death
  • PECAM1 and the Src family kinase LYN inhibit platelet activation by the glycoprotein VI (GP6) collagen receptor
  • PECAM1 and CEACAM1 play essential roles in vascular sprouting
  • normally functions to dampen systemic cytokine levels during LPS-induced endotoxemia by diminishing the accumulation of cytokine-producing leukocytes at sites of inflammation, rather than by modulating cytokine synthesis by leukocytes
  • PECAM1 and CD99 are involved in the reverse transmigration (RT) of tissue-resident dendritic cells (DCs) across lymphatic endothelial cells (LECs) and similar mechanisms promote both diapedesis and RT
  • regulates both constitutive and inflammation-induced T cell migration
  • integrated adhesive and signaling functions of PECAM1 molecules exert a complex regulation of T cell trafficking, a process that is differentially adapted depending on cell-specific expression, and the presence of inflammatory conditions
  • promote macrophage recruitment into lesions developing in areas of low shear stress
  • is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution
  • regulatory role of PECAM1 in venous thrombus resolution, suggesting a predictive value of soluble PECAM1 for postthrombotic syndrome (PTS) after acute deep vein thrombosis (DVT)
  • adhesive properties of PECAM1 are regulatable suggesting novel approaches for controlling endothelial cell migration and barrier function in a variety of vascular permeability disorders
  • plays an important role in the formation of TJ complex
  • specific role of PECAM1 in flow-mediated GAB1 tyrosine phosphorylation and eNOS signaling in endothelial cells
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text
  • tethering of dying cells to phagocytes
  • angiogenesis
  • PATHWAY
    metabolism
    signaling signal transduction
    a component PECAM1/PTPN11 complexes, formed in a LYN-dependent manner, suppress GP6 signaling
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds tyrosine-phosphorylated beta-catenin and modulates beta-catenin localization and sequestration
  • gamma-catenin interaction occurs via an exon 13-mediated process
  • interacting with CD177
  • may interact with BRKB2 and regulate Gprotein-coupled receptors and G proteins functions
  • may form a mecanosensitive complex with GNA11 that would be a critical mediator of vascular diseases
  • is associated with TEK, becomes phosphorylated on its ITIMs, and recruits the inhibitory phosphatases PTPN6 and PTPN11
  • in addition, PECAM1 is associated with CDH5 and may similarly regulate its signaling via recruitment of PTPN6/PTPN11
  • is a target of TP53 in T cells and TP53 contributes to T cell homeostasis through the induction of the pro-apoptotic SH2D1A
  • SH2D1A directly and specifically interacts with the cytosolic tyrosine 686 of PECAM1
  • functional link between HMOX1 gene expression and PECAM1 in human endothelial cells, which might play a critical role in the regulation of inflammation
  • endothelial LSP1 modulates extravascular neutrophil chemotaxis by regulating nonhematopoietic vascular PECAM1 expression
  • key molecule in an endothelial mechanosensing complex, specifically mediating GAB1 tyrosine phosphorylation and its downstream AKT1 and eNOS activation
  • cell & other
  • does bind heparin/heparan sulfate by a site distinct from that required for homophilic binding
  • REGULATION
    Other
  • phosphorylated after cellular activation
  • ATP5J down-regulates PECAM1 expression via c-Src activation and attenuates shear-induced nitric oxide release
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in clear cell renal carcinoma with good outcome
    tumoral        
    coexpression of TP53 and PECAM1 in astrogliomas is increased as the tumor grade is increasing
    constitutional     --low  
    in preeclamptic placenta
    Susceptibility
    Variant & Polymorphism SNP , other
  • Leu125val polymorphism and PECAM1 levels are associated with ischemic stroke in Chinese population
  • delta15 isoform is expressed in brain, testis and ovary, at cell surface of platelets, HUVECs, Jurkat T-cell leukemia, HEL, and U937 histiocytic lymphoma cell lines, but is unable to protect against apoptosis
  • SNP affects monocyte adhesion to endothelial cells
  • G+1688A is associated with myocardial infarction (MI) and the allele A might be a risk factor for MI in the Chinese population
    Candidate gene
    Marker estimation of TP53 and PECAM1 could be used as good tools to assess the grade, prognosis and aggressiveness of the astroglial tumors
    Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    targeting PECAM-1 represents a tumor microenvironment -targeted therapeutic approach that suppresses even lethal, end-stage metastatic progression, until now a refractory clinical entity
    reproductionpregnancyplacenta
    promoting PECAM1 expression may be good therapeutic approaches to prevent preeclampsia (PE) symptoms in the future
    ANIMAL & CELL MODELS