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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
Corresponding disease
ACOGS ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects)
ARVC14 arrhythmogenic right ventricular cardiomyopathy 14
Location 18q12.1      Physical location : 25.530.929 - 25.757.445
Synonym name
  • N-cadherin
  • CD325 antigen
  • neural cadherin
  • calcium-dependent adhesion protein, neuronal
  • Synonym symbol(s) NCAD, CDHN, CD325, CDw325, N-CAD, NCDH
    DNA
    TYPE functioning gene
    STRUCTURE 244.25 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure a CCG repeat in 5'utr
    MAPPING cloned Y linked N status confirmed
    Map cen - D18S478 - D18S1151 - CDH2 - D18S847 - D18S463 - qter
    Physical map
    CABYR 18q11.1 calcium-binding tyrosine-(Y)-phosphorylation regulated (fibrousheathin 2) OSBPL1A 18q11-q12 oxysterol binding protein-like 1A IMPACT 18q11.2-q12.1 hypothetical protein IMPACT HRH4 18q11.2 histamine receptor H4 LOC390843 18 similar to hypothetical protein BC005868 LOC342741 18q11.2 similar to DEAD (Asp-Glu-Ala-Asp) box polypeptide 48 LOC147468 18q11.2 similar to WW domain binding protein 2 EHZF 18q11.2 early hematopoietic zinc finger SS18 18q11.2 synovial sarcoma translocation, chromosome 18 MGC26605 18q11.2 hypothetical protein MGC26605 TAF4B 18q11.2 TAF4b RNA polymerase II, TATA box binding protein (TBP)-associated factor, 105kDa KCTD1 18 potassium channel tetramerisation domain containing 1 LOC388472 18 hypothetical gene supported by BC002568 LOC342695 18q12.1 similar to ubiquitin fusion degradation 1-like AQP4 18q11.2.q12.1 aquaporin 4 FLJ30507 18q12.1 hypothetical protein FLJ30507 CHST9 18q11.2 carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 9 LOC342697 18q12.1 similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) CDH2 18q11.2-q12.2 cadherin 2, type 1, N-cadherin (neuronal) LOC390844 18 similar to Ariadne-2 protein homolog (ARI-2) (Triad1 protein) (HT005) DSC3 18q12.1 desmocollin 3 DSC2 18q12.1 desmocollin 2 DSC1 18q12.2 desmocollin 1 DSG1 18q12.1 desmoglein 1 DSG4 18q12.1 desmoglein 4 DSG3 18q12.1 desmoglein 3 (pemphigus vulgaris antigen) DSG2 18q12.1 desmoglein 2 TTR 18q12.1-q12.2 transthyretin (prealbumin, amyloidosis type I) B4GALT6 18q11 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 6
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 4016 97 906 - 2018 30242148
    15 - 3908 - 875 - 2018 30242148
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly Homo sapiens
    Digestiveintestinesmall intestine   
    Endocrineadrenal gland   highly
     neuroendocrinepituitary  highly
    Nervousbraindiencephalonamygdala   Mus musculus
     brainlimbic systemhippocampus   Mus musculus
     braindiencephalonhypothalamus   Mus musculus
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmoothvessel   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text expressed at the time of gastrulation and neurulation
    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
  • 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