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FLASH GENE
Symbol CDH2 contributors: shn/pgu - updated : 19-11-2019
HGNC name cadherin 2, type 1, N-cadherin (neuronal)
HGNC id 1759
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal hydrophobic domain, large N-terminal extracellular domain composed of five tandem repeat domains, termed cadherin repeats that contain four Ca2+-binding sites, and are involved in homotypic protein–protein interactions
  • a transmembrane (1TM) segment and a highly conserved cytoplasmic tail
  • cytoplasmic domain containing two main binding regions, the C-terminal domain (CTD) and the juxtamembrane domain (JMD)
    • secondary structure a cadherin pro-region, five EC repeats of about 110 residues, each of which fold into seven anti-parallel beta strands arranged into two beta sandwich folds, a transmembrane region and a cytoplasmic tail
    conjugated GlycoP , RiboP
    HOMOLOGY
    interspecies ortholog to Cdh2, Mus musculus
    ortholog to Cdh2, Rattus norvegicus
    ortholog to cdh2, Danio rerio
    ortholog to CDH2, Pan troglodytes
    Homologene
    FAMILY
  • cadherin superfamily
    • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • observed in the cytoplasm, was actively internalized by endocytosis
    • basic FUNCTION
  • N-cadherin plays a critical role in early heart development as well as in other morphogenetic processes
  • putatively involved in synaptic adhesion, axon outgrowth
    • and guidance
  • cell-cell or cell-ECM interactions
  • required for establishment of left-right asymmetry during gastrulation
  • maybe involved in establishment of embryonic left-right asymetry
  • regulates dendritic spine morphogenesis and related synaptic functions, presumably cooperating with cadherin-independent adhesive mechanisms to maintain spine-axon contacts
  • mediates apical adhesion between retina epithelial cells
  • calcium-dependent cell adhesion molecule that is associated with invasive tumors in breast cancer
  • modifies KCNA5 activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone
  • plays a pivotal role in the maintenance of the progenitor phenotype in cultured limbal epithelial cells
  • cell adhesion molecules that interacts in a homophilic Ca2+-dependent manner through its extracellular ectodomains
  • having specific function in the maintenance of dendrite arbors
  • CDH2 and CDH11 are crucial regulators of postnatal skeletal growth and bone mass maintenance, serving overlapping, yet distinct, functions in the osteogenic lineage
  • with NLGN1, cooperate to control vesicle clustering at nascent synapses
  • intimately involved in neuronal cell adhesion, signaling, differentiation and synapse function
  • acts by postsynaptically accumulating neuroligin-1 and activating its function via the scaffolding molecule MAGI2, leading, in turn, to presynaptic vesicle clustering
  • in neurons, is required to enable neuroligin-1 to exert its vesicle cluster-inducing effect
  • key cell adhesion molecule implicated in chondrogenic differentiation
  • PCDH19 and CDH2 function together to regulate cell adhesion and to mediate morphogenetic movements during brain development
  • important role during dendrite arborization, axon guidance, and synaptogenesis
  • ATP-sensitive protein that is associated with altered Huntington disease CAG striatal cell adhesion and neuritogenesis
  • integrator of adhesion and cytoskeletal signaling required for proper neuronal cell development and synaptic function
  • important for multipolar neurons to polarize their migration toward the cortical plate
  • regulates the proliferation of DA (dopaminergic) progenitors and the differentiation of DA neurons through canonical WNT-CTNNB1 signaling in the ventral midbrain (vMB)
  • is a cell adhesion molecule which is enriched at synapses
  • relocalizes from the periphery to the center of the synapse after transient synaptic stimulation in hippocampal neurons
  • regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus
  • functional role of CDH2 adherens junctions (AJ) in vasomotor regulation
  • plays a vital role in cell adhesion, making it a biologically plausible candidate gene in ARVC pathogenesis (PMID
  • regulates signaling mechanisms required for lens fiber cell elongation and lens morphogenesis
  • important role in neurulation, brain development and regulation of synaptic function
  • importance of CDH2 in angiogenesis
  • CDH2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development
  • essential roles in neural development include neuronal migration and axon pathfinding
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of transmembrane glycoprotein component of adherens junction
  • forms a molecular complex with axin1 and LRP5 involving the LRP5 cytoplasmic tail domain
  • functionally interacts with LRP6 and axin1 in osteoblasts
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • forms heterodimers R-cadherins
  • protein tyrosine phosphatase, non-receptor type 1, PTPN1
  • in retinoblastoma and normal retina N-cadherin associated with alpha-catenin and beta-catenin
  • glutamate receptor 6, GLUR6
  • Presenilin1, PS1
  • RICS-beta-catenin complex
  • cell adhesion molecule-related/down-regulated by oncogenes; surface glycoprotein, Ig superfamily member, CDO and Boc homolog (mouse), BOC
  • cadherin-11, alpha- and beta-catenin, plakoglobin (proportions variable among species), p120ctn and vinculin
  • hemophilic, calcium dependent interactions
  • interacting by its C terminus with the cytoskeleton via beta-catenin
  • Wnt coreceptor LRP5 and regulates canonical Wnt/beta-catenin signaling in osteoblasts
  • CDH2-axin1-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass
  • CDCP1
  • cleaved specifically by the disintegrin and metalloproteinase ADAM10 in its ectodomain
  • on GRIA2, B3GAT1 regulates cell surface stability of GRIA2 by modulating the interaction with CDH2
  • N-cadherins form homophilic interactions with N-cadherins on opposing membranes and these molecular interactions mediate the effect of neuronal activity on promoting dendrite growth, an important aspect of coordinated neural circuit development
  • mechanistic link among the cell adhesion molecule, CDH2, the actin-binding scaffold protein, CTTN, and KCNA5 remodeling in the heart
  • its expression facilitates cis-dimerization of APP (
  • SHROOM3 and CDH2 function cooperatively downstream of PITX2 to directly regulate cell shape changes necessary for early gut tube morphogenesis
  • adhesion by the PCDH19-CDH2 complex was unaffected by mutations that disrupt CDH2 homophilic binding but was inhibited by a mutation in PCDH19
  • CDH2 engagement mediates neuronal cell survival by enhancing the MAP kinase pathway and down-regulating the pro-apoptotic protein BCL2L11
  • BEX2 promoted the progression of glioma by promoting cell migration and invasion, and these effects might be mediated by CDH2 and MMP2
  • CEACAM1 inhibit cell-matrix adhesion and promote cell motility and CDH2 is a crucial protein involved in the processes
  • CDH2 specifically interacts with FBXO45 through two consensus motifs overlapping the site of calcium-binding and dimerization of the cadherin molecule
  • function of desmoplakin in motor nerve regeneration by linking CDH2 to intermediate filaments in regenerating motor axons
  • CDH2 and CDH11 act as regulators of stem cell fate decisions
  • CDON promotes neural crest migration by regulating CDH2 localization
  • CD82 regulates bone marrow homing of acute myeloid leukemia by modulating the molecular organization of CDH2
  • new role for CTNND1 bound to the CDH2 precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface
  • AMOTL1 is an essential effector of the CDH2 mediated endothelial/pericyte junctional complex
  • EXOC4 regulates CDH2 expression by controlling SMAD3 and SMAD4 expression at the basal transcriptional level, thereby modulating cell migration and adhesion
  • periodic expression of PCDH8 in the anterior presomitic mesoderm (PSM) triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites
  • RELN transiently (and not persistently) promotes CDH2-mediated neuronal aggregation
  • INVS could upregulate the expression of CDH2, VIM, MMP2, and MMP9
  • PKD1 enhances the stability of CDH2 on cell membrane and promotes synapse morphogenesis and synaptic plasticity in an activity-dependent manner
  • CDH2 promotes neurite branching and it is required for three synaptic organizers, NLGN1, leucine-rich repeat transmembrane protein 2 (LRRTM2), and CADM1 to stimulate presynaptic differentiation
  • interaction of NECTIN2 with CDH2
  • GJA1 controls neural crest cell migration by directly regulating CDH2 transcription
  • CDH2-signaling via TRIO assembles adherens junctions to restrict endothelial permeability
    • cell & other
    REGULATION
    Other regulated by PSEN1 (PSEN1-mediated delivery of CDH2 to the plasma membrane is important for exerting its physiological function, and control of the state of cell-cell contact)
    cleaved by ADAM10 (cleavage of N-cadherin is essential for chondrocyte differentiation)
    upregulated by RAP1 (
    ASSOCIATED DISORDERS
    corresponding disease(s) ACOGS , ARVC14
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in ductal carcinomas, decreased levels in primary tumors correlate with local recurrence and death in long-term follow-up of patients
    constitutional        
    of either CDH2 or LIN7C disrupts neural tube formation
    constitutional        
    loss of CDH2 alters the actin cytoskeleton, leading to a decrease in the cortical actin-binding protein, CTTN, which associates with KCNA5 channel and regulates its function in the heart
    tumoral     --low  
    by promoter methylation in colorectal cancer patients
    constitutional     --over  
    partially attenuated nucleus pulposus (NP) cell senescence, decreased ROS content and inhibited the activation of the NFKB1 pathway under the high glucose condition
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    is a potential therapeutic target to slow Diabetes-mediated disc nucleus pulposus (NP) degeneration
    ANIMAL & CELL MODELS
  • Homozygous N-cadherin mutant embryos die by Day 10 of gestation
  • in adult mice loss of N-cadherin in osteolineage cells favors bone formation