Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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afadin, adherens junction formation factor(AFDN) afadin, adherens junction formation factor(AFDN) Related Genes Homo sapiens
CYTOBAND 6, 6q27,
GENERIF_SUMMARY RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6., Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain, Results report the solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr., AF6 negatively regulates Rap1-induced cell adhesion., In the Acute Myeloid Leukemia patients, detected MLL rearrangements consisting of MLL/AF6, MLL/AF9, MLL/AF17 , MLL/ELL and MLL partial tandem duplication. MLL rearrangement include chromosome translocation and partial tandem duplication., Loss of afadin is associated with breast cancer, AF6/s-afadin is a candidate for mediating control of cellular growth processes by regulated translocation to the nucleus., c-Src is recruited by AF-6 to cell-cell contact sites, suggesting that c-Src is regulated by a PDZ protein in special cellular locations., AF6 protein is important for spreading of Herpes simplex virus 1 in epithelial cells, two distal surfaces of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1 changes in millisecond dynamics, whereas distal surface 2 undergoes structural rearrangement, JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates beta1 integrin levels and cell migration., Results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis., the interaction between the PDZ domain of afadin (AF6_PDZ) and a series of polypeptides comprising the PDZ-binding motif, was studied., AF6/afadin is a marker of poor outcome in breast cancer, and its loss induces cell migration, invasiveness and tumor growth, Results demonstrate a role for afadin in the regulation of vascular barrier function via coordination of adherens junction-tight junction and p120-catenin-ZO-1 interactions., the Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cell-cell contact sites, promoting the formation of the nectin-based cell-cell adhesion., AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease., JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton., The expression levels of CFTR and AF-6/afadin are significantly downregulated in human colon cancer tissues., MLL-AF6 oncoprotein potentiates the activity of the RAS pathway through retention of AF6 within the nucleus., AF-6/afadin could be a useful selection marker for fertility-sparing therapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial invasion., In pancreatic cancer cells, AF6 is expressed at reduced levels, causing Dvl2 to be upregulated and available to bind and enhance FOXE1-induced trans-activation of Snail, which promotes proliferation and metastasis., This paper deals with AF-6 in mouse, rat, and cow.,
SP_COMMENT disease:A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein., domain:The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich N-terminus domain interacts with F-actin., function:Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton., similarity:Contains 1 dilute domain., similarity:Contains 1 FHA domain., similarity:Contains 1 PDZ (DHR) domain., similarity:Contains 2 Ras-associating domains., subcellular location:Not found at cell-matrix AJs., subunit:Homodimer. Interacts with F-actin, nectin and PVRL3/nectin-3. Essential for the association of nectin and E-cadherin. Isoform 2/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1 and RIT2 (By similarity). Interacts with NRXN1 and BCR.,