Gene Symbol: AF6
Description: afadin, adherens junction formation factor
Alias: AF6, MLL-AF6, MLLT4, l-afadin, afadin, ALL1-fused gene from chromosome 6 protein, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4, myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4, protein AF-6
Species: human
Products:     AF6

Top Publications

  1. Saha V, Lillington D, Shelling A, Chaplin T, Yaspo M, Ganesan T, et al. AF6 gene on chromosome band 6q27 maps distal to the minimal region of deletion in epithelial ovarian cancer. Genes Chromosomes Cancer. 1995;14:220-2 pubmed
    ..6 has been shown to contain at band q27 a minimal region of deletion associated with epithelial ovarian cancers and AF6, a gene disrupted in acute myeloid leukemia with t(6;11)(q27;q23)...
  2. Fournier G, Cabaud O, Josselin E, Chaix A, Adelaide J, Isnardon D, et al. Loss of AF6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth. Oncogene. 2011;30:3862-74 pubmed publisher
    b>Afadin/AF6, an F-actin-binding protein, is ubiquitously expressed in epithelia and has a key role during development, through its regulatory role in cell-cell junction organization...
  3. Mandai K, Nakanishi H, Satoh A, Takahashi K, Satoh K, Nishioka H, et al. Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. J Cell Biol. 1999;144:1001-17 pubmed
    We recently isolated a novel actin filament (F-actin)-binding protein, afadin, that has two isoforms, l- and s-afadins...
  4. Buchert M, Poon C, King J, Baechi T, D Abaco G, Hollande F, et al. AF6/s-afadin is a dual residency protein and localizes to a novel subnuclear compartment. J Cell Physiol. 2007;210:212-23 pubmed
    The AF6/afadin protein is a component of cell membranes at specialized sites of cell-cell contact. Two main splice variants exist, known as l- and s-afadin, respectively...
  5. Mandai K, Nakanishi H, Satoh A, Obaishi H, Wada M, Nishioka H, et al. Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction. J Cell Biol. 1997;139:517-28 pubmed
    ..We named p205 l-afadin (a large splicing variant of AF-6 protein localized at adherens junction) and p190 s-afadin (a small splicing ..
  6. Hock B, Böhme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, et al. PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proc Natl Acad Sci U S A. 1998;95:9779-84 pubmed
    ..the Eph-related RTKs EphA7, EphB2, EphB3, EphB5, and EphB6 interact with the PDZ domain of the ras-binding protein AF6. A mutational analysis revealed that six C-terminal residues of the receptors are involved in binding to the PDZ ..
  7. Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, et al. Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. Cancer Res. 1993;53:5624-8 pubmed
    ..In addition, the AF-6 protein contains the GLGF motif shared with several proteins of vertebrates and invertebrates thought to be involved in signal transduction at special cell-cell junctions. ..
  8. Yamamoto T, Harada N, Kawano Y, Taya S, Kaibuchi K. In vivo interaction of AF-6 with activated Ras and ZO-1. Biochem Biophys Res Commun. 1999;259:103-7 pubmed
    ..Taken together, these results indicate that the Ras-interacting region on AF-6 is structurally similar to that on Raf-1 and on RalGDS and that AF-6 interacts with activated Ras and ZO-1 in vivo. ..
  9. Ebnet K, Schulz C, Meyer Zu Brickwedde M, Pendl G, Vestweber D. Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem. 2000;275:27979-88 pubmed
    ..Our results suggest that JAM can be recruited to intercellular junctions by its interaction with the PDZ domain-containing proteins AF-6 and possibly ZO-1. ..

More Information

Publications133 found, 100 shown here

  1. Severson E, Lee W, Capaldo C, Nusrat A, Parkos C. Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell. 2009;20:1916-25 pubmed publisher
    ..Here, we report that JAM-A is physically and functionally associated with the PDZ domain-containing molecules Afadin and PDZ-guanine nucleotide exchange factor (GEF) 2, but not zonula occludens (ZO)-1, in epithelial cells, and ..
  2. Letessier A, Garrido Urbani S, Ginestier C, Fournier G, Esterni B, Monville F, et al. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer. Oncogene. 2007;26:298-307 pubmed
    ..The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14...
  3. Xiao X, Cheng C, Mruk D. Intercellular adhesion molecule-2 is involved in apical ectoplasmic specialization dynamics during spermatogenesis in the rat. J Endocrinol. 2013;216:73-86 pubmed publisher
    ..Interestingly, ICAM2 was found to associate with β1-integrin, nectin-3, afadin, Src, proline-rich tyrosine kinase 2, annexin II, and actin...
  4. Franco M, Carmena A. Eph signaling controls mitotic spindle orientation and cell proliferation in neuroepithelial cells. J Cell Biol. 2019;: pubmed publisher
    ..core components of the mitotic spindle orientation machinery, including Discs Large1, Mud/NuMA, and Canoe/Afadin, mislocalize in dividing Eph mutant neuroepithelial cells and produce spindle alignment defects in these ..
  5. Yokoyama A, Somervaille T, Smith K, Rozenblatt Rosen O, Meyerson M, Cleary M. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell. 2005;123:207-18 pubmed
  6. Sellers K, Watson I, Gresz R, Raval P, Srivastava D. Cyto-nuclear shuttling of afadin is required for rapid estradiol-mediated modifications of histone H3. Neuropharmacology. 2018;143:153-162 pubmed publisher
    ..In this study we have found that the scaffold protein afadin, (also known as AF-6), undergoes a bi-directional trafficking to both synaptic and nuclear compartment in response ..
  7. Matsuda T, Namura A, Oinuma I. Dynamic spatiotemporal patterns of alternative splicing of an F-actin scaffold protein, afadin, during murine development. Gene. 2019;689:56-68 pubmed publisher
    An F-actin scaffold protein, afadin, comprises two splice variants called l-afadin (a long isoform) and s-afadin (a short isoform)...
  8. Ohama D, Matsuda T, Oinuma I. Differential regional and subcellular localization patterns of afadin splice variants in the mouse central nervous system. Brain Res. 2018;1692:74-86 pubmed publisher
    AF6/afadin is an F-actin scaffold protein that plays essential roles in the organization of cell-cell junctions of polarized epithelia...
  9. Finegan T, Na D, Cammarota C, Skeeters A, Nádasi T, Dawney N, et al. Tissue tension and not interphase cell shape determines cell division orientation in the Drosophila follicular epithelium. EMBO J. 2019;38: pubmed publisher
    ..cortical tension at the apical surface translates into planar division orientation in a manner dependent on Canoe/Afadin, which links actomyosin to adherens junctions...
  10. Li Y, Zhang L, Wang C, Tang X, Chen Y, Wang X, et al. Sevoflurane-induced learning deficits and spine loss via nectin-1/corticotrophin-releasing hormone receptor type 1 signaling. Brain Res. 2019;1710:188-198 pubmed publisher
    ..Hippocampal nectin-1 and L-afadin expression assessed using western blot analysis...
  11. Shah J, Rouaud F, Guerrera D, Vasileva E, Popov L, Kelley W, et al. A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote α-Toxin Cytotoxicity. Cell Rep. 2018;25:2132-2147.e7 pubmed publisher
    ..ADAM10 is locked at junctions through binding of its cytoplasmic C terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores...
  12. Majima T, Takeuchi K, Sano K, Hirashima M, Zankov D, Tanaka Okamoto M, et al. An Adaptor Molecule Afadin Regulates Lymphangiogenesis by Modulating RhoA Activity in the Developing Mouse Embryo. PLoS ONE. 2013;8:e68134 pubmed publisher
    b>Afadin is an intracellular binding partner of nectins, cell-cell adhesion molecules, and plays important roles in the formation of cell-cell junctions...
  13. Micci F, Gorunova L, Agostini A, Johannessen L, Brunetti M, Davidson B, et al. Cytogenetic and molecular profile of endometrial stromal sarcoma. Genes Chromosomes Cancer. 2016;55:834-46 pubmed publisher variants of ZC3H7-BCOR and its reciprocal BCOR-ZC3H7 were identified as was involvement of the CREBBP and MLLT4 genes (both well known leukemia-related genes) in two new fusions...
  14. Zhao X, Wang H, Zhao X, Cheng H, Li W, Liu S, et al. [Study on Immunophenotypes and Gene of Acute Lymphoblastic Leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018;26:947-952 pubmed publisher
    ..4) The quantitative screening of 30 cases of ALL 43 fusion genes found BCR-ABL,TEL-AML1 and E2A-PBX1, MLL-AF6, MLL-AF4, and SIL-TAL1 fusion gene was positive in 1 case each; NGS detection of gane mutations associated with ALL ..
  15. Fujiwara Y, Goda N, Tamashiro T, Narita H, Satomura K, Tenno T, et al. Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site. Protein Sci. 2015;24:376-85 pubmed publisher
    b>Afadin, a scaffold protein localized in adherens junctions (AJs), links nectins to the actin cytoskeleton. Nectins are the major cell adhesion molecules of AJs...
  16. Van Itallie C, Anderson J. Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol. 2014;36:157-65 pubmed publisher
    ..linked to peripheral scaffolding proteins (such as ZO-1, afadin, MAGI1, etc...
  17. Hardin J. Regulating cell-cell junctions from A to Z. J Cell Biol. 2016;213:151-3 pubmed publisher
    ..In this issue, Choi et al. (2016. J. Cell Biol. show that afadin and ZO-1 regulate tension and maintain zonula adherens architecture in response to changes in contractility.
  18. Rowart P, Wu J, Caplan M, Jouret F. Implications of AMPK in the Formation of Epithelial Tight Junctions. Int J Mol Sci. 2018;19: pubmed publisher
    ..AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the TJ-associated protein zonula occludens (ZO)-1, thereby facilitating ZO-1 ..
  19. Saito K, Shiino T, Kurihara H, Harita Y, Hattori S, Ohta Y. Afadin regulates RhoA/Rho-associated protein kinase signaling to control formation of actin stress fibers in kidney podocytes. Cytoskeleton (Hoboken). 2015;72:146-56 pubmed publisher
    ..However, little is known how stress fiber assembly is regulated in podocytes. Here, we found that afadin, an actin filament-binding protein, is required for RhoA/ROCK-dependent formation of actin stress fibers in rat ..
  20. Schmidt A, Lv Z, Großhans J. ELMO and Sponge specify subapical restriction of Canoe and formation of the subapical domain in early Drosophila embryos. Development. 2018;145: pubmed publisher
    Canoe/Afadin and the GTPase Rap1 specify the subapical domain during cellularization in Drosophila embryos. The timing of domain formation is unclear...
  21. Deshpande A, Deshpande A, Sinha A, Chen L, Chang J, Cihan A, et al. AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes. Cancer Cell. 2014;26:896-908 pubmed publisher
    ..epigenetic profiles, precludes abnormal HOXA gene expression, and impairs the transforming ability of MLL-AF9, MLL-AF6, and NUP98-NSD1 fusions-mechanistically distinct HOX-activating oncogenes...
  22. Björkenheim A, Brandes A, Magnuson A, Chemnitz A, Edvardsson N, Poci D. Patient-Reported Outcomes in Relation to Continuously Monitored Rhythm Before and During 2 Years After Atrial Fibrillation Ablation Using a Disease-Specific and a Generic Instrument. J Am Heart Assoc. 2018;7: pubmed publisher
    ..Fifty-four patients completed the generic 36-Item Short-Form Health Survey and the AF-specific AF6 questionnaires before and 6, 12, and 24 months after AF ablation...
  23. Singh B, Hornick A, Krishnamurthy S, Locke A, Mendoza C, Mateo M, et al. The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia. J Virol. 2015;89:7089-96 pubmed publisher
    ..To assess the relevance of the protein afadin, which connects nectin-4 to the actin cytoskeleton, we knocked down its mRNA...
  24. Kobayashi S, Obata M, Hagihara M, Motohashi K, Ito S, Ohshima R, et al. The presence of mature granulocytes/monocytes derived from leukemic cells in MLL-associated leukemia. Int J Hematol. 2009;90:591-596 pubmed publisher
    ..MLL partner genes were AF6, AF9, ELL, and ENL, respectively...
  25. Yoshida T, Iwata T, Takai Y, Birchmeier W, Yamato M, Okano T. Afadin requirement for cytokine expressions in keratinocytes during chemically induced inflammation in mice. Genes Cells. 2014;19:842-52 pubmed publisher
    b>Afadin is a filamentous actin-binding protein and a mediator of nectin signaling. Nectins are Ig-like cell adhesion molecules, and the nectin family is composed of four members, nectin-1 to nectin-4...
  26. Miyata M, Maruo T, Kaito A, Wang S, Yamamoto H, Fujiwara T, et al. Roles of afadin in the formation of the cellular architecture of the mouse hippocampus and dentate gyrus. Mol Cell Neurosci. 2017;79:34-44 pubmed publisher
    ..We previously showed that the cell adhesion molecules nectins and its binding protein afadin play roles in the formation of the mossy fiber synapses which are formed between the mossy fibers of the dentate ..
  27. Elbediwy A, Zihni C, Terry S, Clark P, Matter K, Balda M. Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex. J Cell Biol. 2012;198:677-93 pubmed publisher
    ..Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics. ..
  28. Haskin J, Szargel R, Shani V, Mekies L, Rott R, Lim G, et al. AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease. Hum Mol Genet. 2013;22:2083-96 pubmed publisher
    ..The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. ..
  29. Birukova A, Meng F, Tian Y, Meliton A, Sarich N, Quilliam L, et al. Prostacyclin post-treatment improves LPS-induced acute lung injury and endothelial barrier recovery via Rap1. Biochim Biophys Acta. 2015;1852:778-91 pubmed publisher
    ..By contrast, pharmacologic Epac inhibitor, Rap1 knockdown, or knockdown of cell junction-associated Rap1 effector afadin attenuated EC recovery caused by PC or 8CPT post-treatment...
  30. Matsuzawa K, Himoto T, Mochizuki Y, Ikenouchi J. ?-Catenin Controls the Anisotropy of Force Distribution at Cell-Cell Junctions during Collective Cell Migration. Cell Rep. 2018;23:3447-3456 pubmed publisher
    ..stabilization of activated ?-catenin, in part through the recruitment of the actin-binding proteins, vinculin and afadin. In this way, ?-catenin regulates force sensing, as well as force transmission, through a Rho-mediated feedback ..
  31. Kobayashi R, Kurita S, Miyata M, Maruo T, Mandai K, Rikitake Y, et al. s-Afadin binds more preferentially to the cell adhesion molecules nectins than l-afadin. Genes Cells. 2014;19:853-63 pubmed publisher
    l-Afadin was originally purified from rat brain as an actin filament (F-actin)-binding protein that was homologous to the AF-6 gene product...
  32. Bonello T, Perez Vale K, Sumigray K, Peifer M. Rap1 acts via multiple mechanisms to position Canoe and adherens junctions and mediate apical-basal polarity establishment. Development. 2018;145: pubmed publisher
    ..Current data place the actin-junctional linker Canoe (fly homolog of Afadin) at the top of the polarity hierarchy, where it directs Bazooka/Par3 and adherens junction positioning...
  33. Maruo T, Sakakibara S, Miyata M, Itoh Y, Kurita S, Mandai K, et al. Involvement of l-afadin, but not s-afadin, in the formation of puncta adherentia junctions of hippocampal synapses. Mol Cell Neurosci. 2018;92:40-49 pubmed publisher
    ..It was previously shown that afadin regulates the formation of the PAJs cooperatively with nectin-1, nectin-3, and N-cadherin...
  34. Björkenheim A, Brandes A, Magnuson A, Chemnitz A, Svedberg L, Edvardsson N, et al. Assessment of Atrial Fibrillation-Specific Symptoms Before and 2 Years After Atrial Fibrillation Ablation: Do Patients and Physicians Differ in Their Perception of Symptom Relief?. JACC Clin Electrophysiol. 2017;3:1168-1176 pubmed publisher
    ..Symptom relief was assessed as perceived by patients using the short, validated, AF-specific symptom questionnaire AF6 and as classified by physicians using the European Heart Rhythm Association (EHRA) classification at baseline and ..
  35. Sekaran S, Balaganapathy P, Parsanathan R, Elangovan S, Gunashekar J, Bhat F, et al. Lactational exposure of phthalate causes long-term disruption in testicular architecture by altering tight junctional and apoptotic protein expression in Sertoli cells of first filial generation pubertal Wistar rats. Hum Exp Toxicol. 2015;34:575-90 pubmed publisher
    ..claudin, junctional adhesion molecule, zona occludens protein-1 (ZO-1), zona occludens protein-2 (ZO-2), and afadin-6 (AF-6), increased apoptosis by altering the apoptotic genes Bax, cytochrome c, caspase-8, -9, -3 and ..
  36. Yamamoto H, Mandai K, Konno D, Maruo T, Matsuzaki F, Takai Y. Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin. Brain Res. 2015;1620:139-52 pubmed publisher
    ..b>Afadin, a membrane scaffolding protein, regulates the formation of adherens junctions (AJs) and cell migration to form ..
  37. Labernadie A, Kato T, Brugués A, Serra Picamal X, Derzsi S, Arwert E, et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol. 2017;19:224-237 pubmed publisher
    ..N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent...
  38. Tanaka Okamoto M, Itoh Y, Miyoshi J, Mizoguchi A, Mizutani K, Takai Y, et al. Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium. PLoS ONE. 2014;9:e110549 pubmed publisher
    b>Afadin is an actin filament-binding protein that acts cooperatively in cell adhesion with the cell adhesion molecule nectin, and in directional cell movement with the small G protein Rap1 in a nectin-independent manner...
  39. Burmeister T, Meyer C, Gröger D, Hofmann J, Marschalek R. Evidence-based RT-PCR methods for the detection of the 8 most common MLL aberrations in acute leukemias. Leuk Res. 2015;39:242-7 pubmed publisher
    ..variants, we developed RT-PCR methods for the reliable detection of the 8 most common MLL aberrations (MLL-AF4, MLL-AF6, MLL-AF9, MLL-AF10, MLL-ENL, MLL-ELL, MLL-EPS15, MLL PTD), together accounting for around 90% of MLL-r cases...
  40. Dewitz C, Pimpinella S, Hackel P, Akalin A, Jessell T, Zampieri N. Nuclear Organization in the Spinal Cord Depends on Motor Neuron Lamination Orchestrated by Catenin and Afadin Function. Cell Rep. 2018;22:1681-1694 pubmed publisher
    ..position to reveal the roles and contributions of cell adhesive function by inactivating N-cadherin, catenin, and afadin signaling...
  41. Chen X, Wang F, Zhang Y, Wang M, Tian W, Teng W, et al. Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia. Leuk Res. 2018;72:99-104 pubmed publisher
    ..BCR-ABL1, TCF3-PBX1, KMT2A-AFF1 and ETV6-RUNX1 were more frequent in B-ALL. On the contrary, KMT2A-MLLT4, SET-NUP214 and STIL-TAL1 were of higher incidence in T-ALL...
  42. Saito S, Matsushima M, Shirahama S, Minaguchi T, Kanamori Y, Minami M, et al. Complete genomic structure DNA polymorphisms, and alternative splicing of the human AF-6 gene. DNA Res. 1998;5:115-20 pubmed
    ..These results may contribute to an understanding of the mechanism causing chromosomal translocations in leukemic cells. ..
  43. Umeda K, Iwasawa N, Negishi M, Oinuma I. A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner. Mol Biol Cell. 2015;26:1957-70 pubmed publisher
    ..We recently identified afadin, an F-actin-binding protein, as an effector of R-Ras mediating axon branching through F-actin reorganization...
  44. Numata A, Kwok H, Kawasaki A, Li J, Zhou Q, Kerry J, et al. The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia. Nat Commun. 2018;9:1622 pubmed publisher
    ..Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL-rearranged AMLs...
  45. Deshpande A, Chen L, Fazio M, Sinha A, Bernt K, Banka D, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood. 2013;121:2533-41 pubmed publisher
    ..In this study, we demonstrate that MLL-AF6 requires continued activity of the histone-methyltransferase DOT1L to maintain expression of the MLL-AF6-driven ..
  46. Nagy J, Lynn B. Structural and Intermolecular Associations Between Connexin36 and Protein Components of the Adherens Junction-Neuronal Gap Junction Complex. Neuroscience. 2018;384:241-261 pubmed publisher
    ..junction-associated proteins α-catenin and β-catenin, as well as the proteins zonula occludens-1 and AF6 (aka, afadin) that were reported constituents of both adherens junctions and gap junctions...
  47. Shah J, Guerrera D, Vasileva E, Sluysmans S, Bertels E, Citi S. PLEKHA7: Cytoskeletal adaptor protein at center stage in junctional organization and signaling. Int J Biochem Cell Biol. 2016;75:112-6 pubmed publisher
    ..PLEKHA7 interacts with cytoplasmic components of the AJ (p120-catenin, paracingulin, afadin), stabilizes the E-cadherin complex by linking it to the minus ends of noncentrosomal microtubules, and stabilizes ..
  48. Choi W, Acharya B, Peyret G, Fardin M, Mège R, Ladoux B, et al. Remodeling the zonula adherens in response to tension and the role of afadin in this response. J Cell Biol. 2016;213:243-60 pubmed publisher
    ..Cells respond to elevated contractility by increasing junctional afadin. Although ZO/afadin knockdown did not prevent contractile array assembly, it dramatically altered cell shape and ..
  49. Sai K, Wang S, Kaito A, Fujiwara T, Maruo T, Itoh Y, et al. Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses. J Comp Neurol. 2017;525:2719-2734 pubmed publisher
    ..Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin-deficient mice...
  50. Azizoglu D, Braitsch C, MARCIANO D, Cleaver O. Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis. Genes Dev. 2017;31:2376-2390 pubmed publisher
    ..We show that loss of the scaffolding protein Afadin disrupts de novo lumenogenesis and lumen continuity in the tip epithelium...
  51. Popovic M, Bella J, Zlatev V, Hodnik V, Anderluh G, Barlow P, et al. The interaction of Jagged-1 cytoplasmic tail with afadin PDZ domain is local, folding-independent, and tuned by phosphorylation. J Mol Recognit. 2011;24:245-53 pubmed publisher
    ..Binding of Jagged-1 intracellular region to the PDZ domain of afadin, a protein located at cell-cell adherens junctions, couples Notch signaling with the adhesion system and the ..
  52. Birukova A, Fu P, Wu T, Dubrovskyi O, Sarich N, Poroyko V, et al. Afadin controls p120-catenin-ZO-1 interactions leading to endothelial barrier enhancement by oxidized phospholipids. J Cell Physiol. 2012;227:1883-90 pubmed publisher
    b>Afadin is a novel regulator of epithelial cell junctions assembly. However, its role in the formation of endothelial cell junctions and the regulation of vascular permeability remains obscure...
  53. Kurita S, Ogita H, Takai Y. Cooperative role of nectin-nectin and nectin-afadin interactions in formation of nectin-based cell-cell adhesion. J Biol Chem. 2011;286:36297-303 pubmed publisher
    The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins...
  54. Keder A, Rives Quinto N, Aerne B, Franco M, Tapon N, Carmena A. The hippo pathway core cassette regulates asymmetric cell division. Curr Biol. 2015;25:2739-2750 pubmed publisher with the ACD modulators Inscuteable and Bazooka in vivo and phosphorylates Canoe, the ortholog of Afadin/AF-6, in vitro...
  55. Fu J, Luo Y, Miao S, Wang L. [Expression Patterns of the Proteins Associated with Cell Junctions in Mouse Testes]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016;38:205-9 pubmed publisher
    ..The adaptor proteins associated with cell juctions zonula occludens-1, zonula occludens-2, Afadin, ?-catenin, and CD2-associated protein were not stage-specific in the seminiferous tubules in the mouse testes...
  56. Radziwill G, Weiss A, Heinrich J, Baumgartner M, Boisguerin P, Owada K, et al. Regulation of c-Src by binding to the PDZ domain of AF-6. EMBO J. 2007;26:2633-44 pubmed
    ..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. We identified a novel type of c-Src regulation by interaction with a PDZ protein. ..
  57. Rakotomamonjy J, Brunner M, Jüschke C, Zang K, Huang E, Reichardt L, et al. Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia. Neural Dev. 2017;12:7 pubmed publisher
    ..Conditional deletion of Afadin, a protein required for formation and maintenance of epithelial tissues, leads to abnormalities in radial glial ..
  58. Taya S, Yamamoto T, Kano K, Kawano Y, Iwamatsu A, Tsuchiya T, et al. The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme. J Cell Biol. 1998;142:1053-62 pubmed
    ..Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6. ..
  59. Higuchi Y, Tokunaga K, Watanabe Y, Kawakita T, Harada N, Yamaguchi S, et al. Lineage switch with t(6;11)(q27;q23) from T-cell lymphoblastic lymphoma to acute monoblastic leukemia at relapse. Cancer Genet. 2016;209:267-71 pubmed publisher
    ..Marrow cells at both the 5th lymphoid and 6th myeloid relapses had t(6;11)(q27;q23) and the same MLL-MLLT4 fusion transcript...
  60. Beati H, Peek I, Hordowska P, Honemann Capito M, Glashauser J, Renschler F, et al. The adherens junction-associated LIM domain protein Smallish regulates epithelial morphogenesis. J Cell Biol. 2018;217:1079-1095 pubmed publisher
    ..Smash also binds to Canoe/Afadin and the tyrosine kinase Src42A and localizes to the ZA in a planar polarized fashion...
  61. Linnemann T, Geyer M, Jaitner B, Block C, Kalbitzer H, Wittinghofer A, et al. Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily. J Biol Chem. 1999;274:13556-62 pubmed
    ..A potential candidate is AF6 which was originally identified as a fusion to ALL-1 in acute myeloid leukemia...
  62. Asada M, Irie K, Morimoto K, Yamada A, Ikeda W, Takeuchi M, et al. ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions. J Biol Chem. 2003;278:4103-11 pubmed
    b>Afadin is an actin filament (F-actin)-binding protein that is associated with the cytoplasmic tail of nectin, a Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecule...
  63. Tsurumi H, Kurihara H, Miura K, Tanego A, Ohta Y, Igarashi T, et al. Afadin is localized at cell-cell contact sites in mesangial cells and regulates migratory polarity. Lab Invest. 2016;96:49-59 pubmed publisher
    ..During the search for proteins regulating the morphology of mesangial cells, we found that afadin, a multi-domain F-actin-binding protein, and β-catenin are expressed in cell-cell contact sites of cultured ..
  64. Carminati M, Gallini S, Pirovano L, Alfieri A, Bisi S, Mapelli M. Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation. Nat Struct Mol Biol. 2016;23:155-63 pubmed publisher
    ..We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts...
  65. Tian Y, Gawlak G, O Donnell J, Birukova A, Birukov K. Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch. J Biol Chem. 2016;291:10032-45 pubmed publisher
    ..18% CS-induced EC permeability was linked to dissociation of cell junction scaffold afadin from the adherens junctions...
  66. Perez White B, Ventrella R, Kaplan N, Cable C, Thomas P, Getsios S. EphA2 proteomics in human keratinocytes reveals a novel association with afadin and epidermal tight junctions. J Cell Sci. 2017;130:111-118 pubmed publisher
    ..b>Afadin (AFDN), a cytoskeletal and junction-associated protein, was present in 2D and 3D keratinocyte cultures, and ..
  67. Feng L, Houck J, Lohavanichbutr P, Chen C. Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa. Oncotarget. 2017;8:31521-31531 pubmed publisher
    ..HCG22, FLG-AS1, CCL14/CCL15-CCL14, LOC100506990, TRIP10, PCBP1-AS1, LINC01315, LINC00478, COX10-AS1/LOC100506974, MLLT4-AS1, MIR31HG, and DUXAP10/LINC01296...
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    ..Altogether, we propose the Dizzy, Rap1 and Cno pathway and Mbt converge in regulating the interface between Bazooka and AJ material to promote ZA morphogenesis. ..
  69. Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, et al. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. J Cell Biol. 1999;145:539-49 pubmed
    We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines...
  70. Geng X, Maruo T, Mandai K, Supriyanto I, Miyata M, Sakakibara S, et al. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes Cells. 2017;22:715-722 pubmed publisher
    ..and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number ..
  71. Tagashira T, Fukuda T, Miyata M, Nakamura K, Fujita H, Takai Y, et al. Afadin Facilitates Vascular Endothelial Growth Factor-Induced Network Formation and Migration of Vascular Endothelial Cells by Inactivating Rho-Associated Kinase Through ArhGAP29. Arterioscler Thromb Vasc Biol. 2018;38:1159-1169 pubmed publisher
    We previously reported that afadin, an actin filament-binding protein, regulated vascular endothelial growth factor-induced angiogenesis. However, the underlying molecular mechanisms are poorly understood...
  72. Ney Garcia D, de Souza M, de Figueiredo A, Othman M, Rittscher K, Abdelhay E, et al. Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes. Hematol Oncol. 2016;: pubmed publisher
    ..MLLT3 was present in five patients, all with acute lymphoblastic leukemia, MLLT1 in two patients, and MLLT10, MLLT4, MLLT11, and AFF1 in one patient each...
  73. Vasileva E, Sluysmans S, Bochaton Piallat M, Citi S. Cell-specific diversity in the expression and organization of cytoplasmic plaque proteins of apical junctions. Ann N Y Acad Sci. 2017;1405:160-176 pubmed publisher
    ..analyses show that the expression profiles of cingulin, paracingulin, ZO-1, ZO-2, ZO-3, PLEKHA7, afadin, PDZD11, p120-catenin, and α-catenin, as well as the transmembrane junctional proteins occludin, E-cadherin, ..
  74. Poon C, Madawala R, Dowland S, Murphy C. Nectin-3 Is Increased in the Cell Junctions of the Uterine Epithelium at Implantation. Reprod Sci. 2016;23:1580-1592 pubmed
    ..while nectin-3 localized to the tight junction at the time of implantation, it did not interact with occludin or l-afadin. These results suggest that at the time of implantation, nectin-3 may contribute to the formation of the tight ..
  75. Reymond N, Fabre S, Lecocq E, Adelaide J, Dubreuil P, Lopez M. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem. 2001;276:43205-15 pubmed
    ..Nectin4 interacts with afadin, a F-actin-associated molecule, via its carboxyl-terminal cytoplasmic sequence...
  76. Reymond N, Garrido Urbani S, Borg J, Dubreuil P, Lopez M. PICK-1: a scaffold protein that interacts with Nectins and JAMs at cell junctions. FEBS Lett. 2005;579:2243-9 pubmed
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    ..This movement does not require the receptor's interaction with the actin-binding adaptor afadin. Interaction of nectin-1 with afadin is also dispensable for virion surfing along nectin-1-rich filopodia...
  78. Bégay Müller V, Ansieau S, Leutz A. The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene. FEBS Lett. 2002;521:36-8 pubmed
    ..We used the yeast two-hybrid system to identify novel Lmo2 interacting proteins and found that the AF6 protein binds to Lmo2...
  79. Keyser J, Lorger M, Pavlovic J, Radziwill G, Moelling K. Role of AF6 protein in cell-to-cell spread of Herpes simplex virus 1. FEBS Lett. 2007;581:5349-54 pubmed
    AF6 and its rat homologue afadin are multidomain proteins localized at cell junctions and involved in intercellular adhesion. AF6 interacts via its PDZ domain with nectin-1 at epithelial adherens junctions...
  80. Niu X, Chen Q, Zhang J, Shen W, Shi Y, Wu J. Interesting structural and dynamical behaviors exhibited by the AF-6 PDZ domain upon Bcr peptide binding. Biochemistry. 2007;46:15042-53 pubmed
    ..The significance of the different response patterns in the signaling pathway and its relevance to the function of the AF-6 PDZ domain should be studied further. ..
  81. Sun T, Wang Y, Cheng H, Xiao H, Xiang J, Zhang J, et al. Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer. Biochim Biophys Acta. 2014;1843:618-28 pubmed
    ..Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer...
  82. Pokutta S, Drees F, Takai Y, Nelson W, Weis W. Biochemical and structural definition of the l-afadin- and actin-binding sites of alpha-catenin. J Biol Chem. 2002;277:18868-74 pubmed
    ..alpha-Catenin is also required for the colocalization of the nectin/afadin/ponsin adhesion system to adherens junctions, and it specifically associates with the nectin-binding protein ..
  83. Maruo T, Mandai K, Miyata M, Sakakibara S, Wang S, Sai K, et al. NGL-3-induced presynaptic differentiation of hippocampal neurons in an afadin-dependent, nectin-1-independent manner. Genes Cells. 2017;22:742-755 pubmed publisher
    ..We have previously shown using afadin-deficient mice that afadin plays multiple roles in the structural and functional differentiations of this synapse...
  84. Joh T, Yamamoto K, Kagami Y, Kakuda H, Sato T, Yamamoto T, et al. Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus. Oncogene. 1997;15:1681-7 pubmed
    ..In the present study, MLL-AF6 chimeric products found in the t(6;11)(q27;q23) translocation were analysed since AF6, a Ras-binding protein, ..
  85. Boettner B, Govek E, Cross J, Van Aelst L. The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin. Proc Natl Acad Sci U S A. 2000;97:9064-9 pubmed
    ..To our knowledge, AF-6 is the only integral component in cell-cell junctions discovered thus far that interacts with profilin and thus could modulate actin modeling proximal to adhesion complexes. ..
  86. Radziwill G, Erdmann R, Margelisch U, Moelling K. The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain. Mol Cell Biol. 2003;23:4663-72 pubmed
    ..We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. ..
  87. Minaguchi T, Matsushima M, Saito S, Kanamori Y, Shirahama S, Okamoto S, et al. Complete DNA sequence and characterization of a 330-kb VNTR-rich region on chromosome 6q27 that is commonly deleted in ovarian cancer. DNA Res. 1999;6:131-6 pubmed
    ..The polymorphic markers and the transcript map documented here may contribute to identification of novel genes or allelic aberrations associated with the development of ovarian cancers. ..
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  89. Taya S, Yamamoto T, Kanai Azuma M, Wood S, Kaibuchi K. The deubiquitinating enzyme Fam interacts with and stabilizes beta-catenin. Genes Cells. 1999;4:757-67 pubmed
    ..These results indicate that Fam interacts with and stabilizes beta-catenin in vivo, presumably through the deubiquitination of beta-catenin. ..
  90. Monteiro A, Sumagin R, Rankin C, Leoni G, Mina M, Reiter D, et al. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell. 2013;24:2849-60 pubmed publisher
    ..Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c...
  91. Bouchard M, Dong Y, McDermott B, Lam D, Brown K, Shelanski M, et al. Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions. Mol Cell Biol. 2000;20:2865-73 pubmed
    ..Nectin-2 is a component of cell-cell adherens junctions and interacts with l-afadin, an F-actin-binding protein...
  92. Zhou H, Xu Y, Yang Y, Huang A, Wu J, Shi Y. Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. J Biol Chem. 2005;280:13841-7 pubmed
    ..Unlike the canonical class II PDZ domain, Ala74 at alphaB5 rather than the residue at alphaB1 makes direct hydrophobic contact with the side chain of Tyr at the -2 position of the ligand. ..