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Symbol AFDN contributors: mct - updated : 06-02-2018
HGNC name afadin
HGNC id 7137
Location 6q27      Physical location : -
Synonym name
  • GTP-Ha-Ras binding cytoplasmic protein AF-6 (afadin)
  • ALL1-fused gene from chromosome 6 protein
  • myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4
  • Synonym symbol(s) AF6, AFADIN, AF-6, FLJ34371, RP3-431P23.3, MLLT4
    TYPE functioning gene
    STRUCTURE 145.03 kb     30 Exon(s)
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    30 - 7629 - 1651 - 2015 25808489
  • S-afadin
  • contains RA domains but lacks the F-actin-binding domain
  • is an endogenous inhibitor of cortical axon branching
  • acts as a dominant-negative isoform in RRAS-AFDN-regulated axon branching
  • more preferentially bound to nectins than l-afadin
  • 32 - 7459 - 1743 - 2012 22948147
  • AF6i3
  • 33 - 7750 - 1781 - 2014 25263091
  • L-afadin with an F-actin binding motif
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Hearing/Equilibriumearinnercochlea highly
    Nervousbrainlimbic systemhippocampus   Homo sapiens
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text pancreas
  • two N terminal Ras-binding-domains (RBD)
  • U104 and DIL motifs described respectively in microtubules and actin-based motor proteins
  • a PDZ domain (AFPDZ) responsible for binding the cytoplasmic C-terminus of nectins
  • an F-actin binding domain to connect the cytoskeleton with transmembrane proteins at cellular junctions
  • Ras binding sites that interact with and regulate the small GTPases RAS and RAP1 (Ras association (RA) domains, effector of RRas inducing axon branching through F-actin reorganization)
  • an extended C terminal tail interferred with proline-rich patches
    interspecies homolog to trithorax Drosophila
    homolog to afadin,large (p205) and small (p190) varieties of AF-6 protein
    CATEGORY adhesion , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
  • synaptic localization for PVRL1 and MLLT4 are F-actin-dependent and the shedding of PVRL1 is a mechanism contributing to synaptic plasticity
  • located at cell-cell adherens junctions
  • key component of epithelial junctions
  • localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle
  • basic FUNCTION
  • may be acting as an intracellular signaling component controlled by ras signaling pathways
  • plays a role in formation and maintenance of cell junctions
  • involved not only in the assembly of nectins and cadherins at synapses, but also in synaptic remodeling
  • has a key role during development, through its regulatory role in cell-cell junction organization
  • plays crucial roles, independently of the role as the nectin-afadin module, in barrier function and homeostasis of the intestinal epithelia
  • LRPAP1-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other cell adhesion molecules and receptors
  • key intracellular signaling molecule for cadherin recruitment and is necessary for spine and synapse formation
  • may be a target for cAMP/RAPGEF3/RAP1A signalling at electrical synapses
  • is required for the maintenance of dendritic structure and excitatory tone
  • is required for the maintenance of dendritic architecture and excitatory inputs
  • is likely required for the proper maintenance of dendritic fields through the coordinated regulation of both synapse number and function
  • is essential for the maintenance of Adherens junctions (AJs) in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain
  • regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons
  • is an important regulator of cell-cell adhesion
  • filamentous actin-binding protein and a mediator of nectin signaling
  • remarkable function of afadin, which was able to enhance cytokine expression through TERF2IP activation in keratinocytes during inflammation
  • is a potential inhibitor of metastasis in pancreatic cancer cells
  • afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse
  • F-actin-binding protein afadin is required for lumen continuity in developing renal tubules
  • is required for lumen continuity by orienting the mitotic spindle during cell division
    a component
  • dimerization facilitates formation of a complex with MLLT4 and PDZGEF2 that activates RAP1A, which regulates beta1 integrin levels and cell migration
    small molecule
  • binding partner of RAP1A, associating with profilin (PFN*), TJP1, occludin (OCLN)
  • interacting with SRC (SRC colocalizes with MLLT4 at cell
  • cell junctions in epithelial cells, and stimulation of cells with EGF increases MLLT4-dependent recruitment of SRC to these sites)
  • binding of MLLT4 to RAP1A regulated the activity of RAP1A in a positive-feedback manner
  • binding of JAG1 intracellular region to the PDZ domain of afadin couples Notch signaling with the adhesion system and the cytoskeleton
  • interacts with the cytoplasmic region of nectins, which are immunoglobulin-like cell adhesion molecules at adherens junctions, and links them to the actin cytoskeleton
  • association of GJD2 with MLLT4 and MPDZ, which required the C-terminus PDZ domain interaction motif of GJD2 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MPDZ
  • interaction with RRAS in cortical neurons during the stage of axonal development
  • afadin directly interacts with GRIA2, potentially via its type II PDZ domain, mechanistically linking the coordination of surface expression of AMPARs to synapse and dendrite structure
  • PLEKHA7 bound to AFDN in addition to CTNND1 and was associated with nectin by binding to AFDN
  • links nectins to the actin cytoskeleton
  • critical role of the AFDN-ARHGAP29 axis for the regulation of RHO-associated kinase activity during vascular endothelial growth factor-induced network formation and migration of HUVECs
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with HRX (MLL), in acute myeloid leukemia with translocation t(6;11)(q27;q23) in a VNTR rich region (see ST8)
    tumoral     --low  
    in tumors correlates with high tumor size and poor metastasis-free survival in patients
    tumoral     --low  
    in Pancreatic cancer
    constitutional   deletion    
    causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain
    Variant & Polymorphism
    Candidate gene
    Therapy target