Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CD2AP contributors: shn/mct - updated : 13-09-2016
HGNC name CD2-associated protein
HGNC id 14258
Corresponding disease
FSGS3 focal segmental glomerulosclerosis 3
Location 6p12.3      Physical location : 47.445.524 - 47.594.994
Synonym name
  • cas ligand with multiple SH3 domains
  • adapter protein CMS
  • cas ligand with multiple Src homology 3 (SH3) domains
  • Synonym symbol(s) CMS, DKFZP586H0519, FSGS3
    DNA
    TYPE functioning gene
    STRUCTURE 149.47 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • region between -558 and -1bp ahead of the transcription start point is indispensable for the promoter activity of the human CD2AP gene
  • A CREB site and two Sp1 sites were essential for maintaining the basal transcriptional activity of the human CD2AP promoter (not only CREB but also Sp1 plays a critical role in regulating basal CD2AP promoter activity in renal tubular epithelial cells)
  • overexpression of E2F1 transactivates the CD2AP promoter ( E2F1 can bind to Sp1 binding site and overexpression of E2F1 is capable of increasing the binding of E2F1 and decreasing the binding of Sp1 to Sp1 binding sites)
  • MAPPING cloned Y linked N status provisional
    Map pter - D6S452 - D6S1651 - CD2AP - D6S1566 - D6S1669 - cen
    Physical map
    RUNX2 6p21 runt-related transcription factor 2 CLIC5 6p12.1-21.1 chloride intracellular channel 5 ENPP4 6p21.1-p11.2 ectonucleotide pyrophosphatase/phosphodiesterase 4 (putative function) ENPP5 6p21.1-p11.2 ectonucleotide pyrophosphatase/phosphodiesterase 5 (putative function) ACTGP9 6p21.1 actin, gamma pseudogene 9 DSCR1L1 6p21-p11 Down syndrome critical region gene 1-like 1 LOC340211 6p21.1 similar to LINE-1 REVERSE TRANSCRIPTASE HOMOLOG CYP39A1 6p21.1-p11.2 cytochrome P450, family 39, subfamily A, polypeptide 1 SLC25A27 6p12.3 solute carrier family 25, member 27 TDRD6 6p21.1 tudor domain containing 6 PLA2G7 6p21.2-p12 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) LOC389394 6 similar to hypothetical protein DKFZp434D2328 MEP1A 6p21.2-p21.1 meprin A, alpha (PABA peptide hydrolase) GPR116 6p12.3 G protein-coupled receptor 116 GPR110 6p21.1 G protein-coupled receptor 110 FLJ22684 6p21.1 hypothetical protein FLJ22684 TNFRSF21 6p21.1-12.2 tumor necrosis factor receptor superfamily, member 21 CD2AP 6p12 CD2-associated protein GPR111 6p12.3 G protein-coupled receptor 111 GPR115 6p12.3 G protein-coupled receptor 115 C6orf138 6p12.3 chromosome 6 open reading frame 138 LOC389395 6 similar to heterogeneous nuclear ribonucleoprotein A3 RBMXP1 6p12.3 RNA binding motif protein, X chromosome pseudogene 1 LOC391925 6 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu) MUT 6p21.2-p21.1 methylmalonyl Coenzyme A mutase
    RNA
    TRANSCRIPTS type messenger
    text
  • region between -558 and -1bp ahead of the transcription start point indispensable for the promoter activity of CD2AP gene
  • CD2AP promoter contains an AP-1-like element
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 5425 71.3 639 expressed in developing podocytes and widely in mature kidney 2000 10997929
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     liver    
    Endocrinepancreas    
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemprostate   
    Urinarykidneynephronrenal capsuleglomerulushighly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Urinarypodocyte Homo sapiens
    cell lineage strongly expressed in glomerular podocytes
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three SH3 domains in the NH2 terminus
  • a coiled-coil domain
  • proline-rich sequences in the center region
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Cd2ap, Mus musculus
    ortholog to Cd2ap, Rattus norvegicus
    ortholog to CD2AP, Pan troglodytes
    Homologene
    FAMILY
    CATEGORY adaptor , immunity/defense , storage
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    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
  • INTERACTION
    DNA
    RNA
  • 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
    protein
  • 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
  • PSTPIP1, ARHGAP27, CAPZA1
  • 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
    REGULATION
    activated by epidermal growth factor (EGF) in renal tubular epithelial cells
    ASSOCIATED DISORDERS
    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
    Susceptibility
  • 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
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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