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Symbol CD2AP contributors: shn/mct - updated : 13-09-2016
HGNC name CD2-associated protein
HGNC id 14258
  • three SH3 domains in the NH2 terminus
  • a coiled-coil domain
  • proline-rich sequences in the center region
  • mono polymer homomer , dimer
    interspecies ortholog to Cd2ap, Mus musculus
    ortholog to Cd2ap, Rattus norvegicus
    ortholog to CD2AP, Pan troglodytes
    CATEGORY adaptor , immunity/defense , storage
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
    text cytoskeleton
    basic FUNCTION
  • facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton
  • critical for stabilizing contacts between T cells and antigen-presenting cells
  • scaffolding molecule that regulates the actin cytoskeleton
  • promoting upregulation of actin stress fiber formation
  • may anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerulus
  • acting as an adapter protein between membrane proteins and the actin cytoskeleton in interphase and during cytokinesis
  • CD2AP-nephrin interactions are critical to maintaining slit diaphragm function and have a role in maintaining specialized subcellular architecture
  • has a role in polycystin-2 function
  • might be a downstream mediator of EGF/EGFR signaling transduction pathway
  • CD2AP/CMS, through interactions with Rab4 and c-Cbl, controls early endosome morphology and may play a role in traffic between early and late endosomes
  • required for early activation of anti-apoptotic phosphatidylinositol 3-kinase (PI3K)/AKT and has a role in maintaining podocyte survival
  • involved in several molecular signaling pathways and is an important factor responsible for nephrotic syndrome
  • scaffold adaptor protein that associates with cortactin, a protein also involved in the regulation of receptor-mediated endocytosis
  • adaptor protein that plays a role in endocytosis, cell motility, and cell survival
  • plays a critical role in the maintenance of the kidney filtration barrier
  • adaptor molecule involved in the internalization of ubiquitinated RTKs, and associated with RET under basal, unstimulated conditions in neurons
  • CD2AP and CBLC, constitute a checkpoint that controls the extent of RET downregulation and, thereby, the sensitivity of neurons to glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs)
  • is a crucial protein for the slit-diaphragm assembly and function
  • participates in antiapoptotic regulation in the human renal tubular epithelial cells. Antiapoptotic effect of EGF/CD2AP signal transduction is mediated by JunD and c-fos
  • scaffolding protein interacting with the nephrin-receptor complex, which is considered to play an important role in the maintenance of the slit diaphragm
  • may play a crucial role in albumin overload-induced ER stress and apoptosis in podocytes
  • adaptor molecule involved in T cell receptor signaling and podocyte homeostasis
  • major function of CD2AP is likely on the actin cytoskeleton, affecting migration to local lymph nodes under conditions of inflammation
  • actin barbed-end capping protein responsible for actin stability at the adherens junction
  • multidomain scaffolding protein that has a critical role in renal function
  • in podocytes serves as an adaptor protein binding to nephrin and podocin, anchoring these slit diaphragm proteins to actin filaments of podocyte cytoskeleton, and sending signals inward or outward
  • role in podocyte apoptosis and proteinuria induced by angiotensin II
    PHYSIOLOGICAL PROCESS immunity/defense
    signaling signal transduction
  • potential signaling pathway between PAX2 and CD2AP in the renal interstitial fibrosis disease
  • Golgi-traversing pathway for exosomal release of the cargo protein GPRC5B in which CD2AP facilitates the entry and LMAN2 impedes the exit of the flux, respectively
  • a component
  • component of the slit membrane of the glomerular podocytes
  • SH3BP1 formed a complex with CGNL1/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein, and both were required for normal CDC42 signaling and junction formation
  • a critical role CREB and Sp1 in regulating basal CD2AP promoter activity in renal tubular epithelial cells
  • EGF activates the human CD2AP promoter in renal tubular epithelial cells
  • EGF-induced JunD/c-fos complexes bind to the human CD2AP gene promoter via an P-1-Like element in human renal tubular epithelial cells
  • small molecule
  • cytoplasmic domain of CD2 molecule
  • proto-oncogenic protein c-Cbl (SH3KBP1)
  • RAB4A, member RAS oncogene family (RAB4A)
  • focal adhesion protein p130(Cas)
  • family with sequence similarity 125, member A (olso known as CFBP)
  • polycystic kidney disease 2 (PKD2)
  • vinculin
  • cortactin binding
  • anillin, a specific cleavage furrow component
  • cytoplasmic domain of nephrosis 1, congenital, Finnish type (nephrin, NPHS1) and nephrosis 2, idiopathic, steroid-resistant (podocin, NPHS2) in podocytes
  • functional competition of CD2AP and SH3KBP1 for binding to nephrin and podocin (when both proteins are coexpressed, nephrin and podocin bind preferentially to CD2AP)
  • INPPL1 interacts with CD2AP in glomeruli and is expressed in podocytes, where it translocates to plasma membrane after insulin stimulation
  • transcription factor SP1 and SP3 up-regulate the basal transcriptional activity of CD2AP and increase CD2AP expression at mRNA level
  • SEPT7 associates with CD2AP and NPHS1, both essential for glomerular ultrafiltration
  • efficient colocalization of capping protein (CP) and CTTN at the cell periphery required CD2AP
  • adaptor protein CD2AP-mediated internalization following cell surface delivery appears to contribute to the Golgi accumulation of GPRC5B, possibly in parallel with biosynthetic/secretory trafficking from the endoplasmic reticulum
  • cell & other
    activated by epidermal growth factor (EGF) in renal tubular epithelial cells
    corresponding disease(s) FSGS3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in Congenital nephrotic syndrome of the Finnish type (CNF)
    constitutional     --low  
    in diabetic conditions in podocytes via PI3-K/Akt signaling
  • to glomerulosclerosis and glomerular disease
  • to Alzheimer disease
  • toend-stage renal disease (ESRD) in patients with type 1 diabetes
  • Variant & Polymorphism SNP
  • strongly associated with Alzheimer disease
  • CD2AP gene variants may contribute to susceptibility to ESRD in patients with type 1 diabetes
  • Candidate gene
    Therapy target
  • CD2AP-deficient mice die at 6 to 7 weeks of age from renal failure. Knockout mice exhibited exhibited nephrotic syndrome and renal failure: defects in epithelial cell foot processes, mesangial cell hyperplasia and extracellular matrix deposition
  • Mice lacking CD2AP exhibit a congenital nephrotic syndrome characterized by extensive foot process effacement
  • Mice lacking CD2AP die at 6 weeks of age. Mice with CD2AP haploinsufficiency developed glomerular changes at 9 months and had increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes