armadillo domain proteins


Summary: A family of proteins that contain several 42-amino acid repeat domains and are homologous to the Drosophila armadillo protein. They bind to other proteins through their armadillo domains and play a variety of roles in the CELL including SIGNAL TRANSDUCTION, regulation of DESMOSOME assembly, and CELL ADHESION.

Top Publications

  1. Hjeij R, Lindstrand A, Francis R, Zariwala M, Liu X, Li Y, et al. ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. Am J Hum Genet. 2013;93:357-67 pubmed publisher
    ..We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs...
  2. Forbes A, Spradling A, Ingham P, Lin H. The role of segment polarity genes during early oogenesis in Drosophila. Development. 1996;122:3283-94 pubmed
  3. Medina M, Marinescu R, Overhauser J, Kosik K. Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome. Genomics. 2000;63:157-64 pubmed
    ..These findings and the properties of delta-catenin as a neuronal-specific protein, expressed early in development and involved in cell motility, support its role in the mental retardation of CDCS when present in only one copy...
  4. Huang X, Wang G, Wu Y, Du Z. The structure of full-length human CTNNBL1 reveals a distinct member of the armadillo-repeat protein family. Acta Crystallogr D Biol Crystallogr. 2013;69:1598-608 pubmed publisher
    ..The structure provides critical insights into the molecular interactions between CTNNBL1 and its protein partners, especially AID. ..
  5. Bienz M, Clevers H. Armadillo/beta-catenin signals in the nucleus--proof beyond a reasonable doubt?. Nat Cell Biol. 2003;5:179-82 pubmed
    ..Plausible explanations allow these observations to be reconciled with the large body of evidence supporting a nuclear function of Arm/beta-catenin. ..
  6. Davis M, Ireton R, Reynolds A. A core function for p120-catenin in cadherin turnover. J Cell Biol. 2003;163:525-34 pubmed
    ..The data reveal a core function of p120 in cadherin complexes, and strongly predict a dose-dependent loss of E-cadherin in tumors that partially or completely down-regulate p120. ..
  7. Oda H, Uemura T, Harada Y, Iwai Y, Takeichi M. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev Biol. 1994;165:716-26 pubmed
    ..All these results suggest that DE-cadherin is a homolog of vertebrate classic cadherins and that the vertebrate and invertebrate share common mechanisms for regulation of cell-cell adhesion. ..
  8. Kessler T, Müller H. Cleavage of Armadillo/beta-catenin by the caspase DrICE in Drosophila apoptotic epithelial cells. BMC Dev Biol. 2009;9:15 pubmed publisher
    ..Our data suggest that N-terminal truncation of Arm by caspases is evolutionarily conserved and thus might provide a principal mechanism involved in the disassembly of adherens junctions during apoptosis. ..
  9. McCartney B, Price M, Webb R, Hayden M, Holot L, Zhou M, et al. Testing hypotheses for the functions of APC family proteins using null and truncation alleles in Drosophila. Development. 2006;133:2407-18 pubmed
    ..Two mutant proteins have dominant effects on cytoskeletal regulation, affecting Wnt-independent nuclear retention in syncytial embryos. However, they do not have dominant-negative effects on Wnt signaling. ..

More Information


  1. Ahmed Y, Hayashi S, Levine A, Wieschaus E. Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development. Cell. 1998;93:1171-82 pubmed
    ..Uncoupling of these two Arm-induced processes suggests a novel role for the Arm/dTCF complex in the activation of apoptosis. ..
  2. Zecca M, Basler K, Struhl G. Direct and long-range action of a wingless morphogen gradient. Cell. 1996;87:833-44 pubmed
    ..We interpret these findings as evidence that Wg can act directly and at long range as a gradient morphogen during normal development. ..
  3. Hatzfeld M, Haffner C, Schulze K, Vinzens U. The function of plakophilin 1 in desmosome assembly and actin filament organization. J Cell Biol. 2000;149:209-22 pubmed
  4. Wodarz A, Stewart D, Nelson W, Nusse R. Wingless signaling modulates cadherin-mediated cell adhesion in Drosophila imaginal disc cells. J Cell Sci. 2006;119:2425-34 pubmed
  5. Hayward P, Balayo T, Martinez Arias A. Notch synergizes with axin to regulate the activity of armadillo in Drosophila. Dev Dyn. 2006;235:2656-66 pubmed
    ..Our results provide evidence for a function of Axin in the regulation of Armadillo that is different from its role as a scaffold for GSK3beta. ..
  6. Peifer M, Berg S, Reynolds A. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994;76:789-91 pubmed
  7. Mariner D, Wang J, Reynolds A. ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes. J Cell Sci. 2000;113 ( Pt 8):1481-90 pubmed
    ..The dual localization of ARVCF to junctions and to nuclei suggests activities in different cellular compartments, as is the case for several other Armadillo repeat proteins including beta-catenin, p120 and the plakophilins. ..
  8. Couillault C, Pujol N, Reboul J, Sabatier L, Guichou J, Kohara Y, et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol. 2004;5:488-94 pubmed
    ..As the activity of tir-1 was independent of the single nematode Toll-like receptor, TIR-1 may represent a component of a previously uncharacterized, but conserved, innate immune signaling pathway. ..
  9. Paulson A, Mooney E, Fang X, Ji H, McCrea P. Xarvcf, Xenopus member of the p120 catenin subfamily associating with cadherin juxtamembrane region. J Biol Chem. 2000;275:30124-31 pubmed
    ..In common with the putative post-translational modifications of the Xarvcf protein, the presence of alternative splice isoforms suggests that Xarvcf possesses the capacity to effect developmental functions in a regulatable manner. ..
  10. Burger M, Tebay M, Keith P, Samaratunga H, Clements J, Lavin M, et al. Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer. Int J Cancer. 2002;100:228-37 pubmed
    ..Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. ..
  11. Townsley F, Bienz M. Actin-dependent membrane association of a Drosophila epithelial APC protein and its effect on junctional Armadillo. Curr Biol. 2000;10:1339-48 pubmed
    ..These filaments may serve as tracks for E-APC to reach the adherens junctions. The failure of E-APC to do so appears to affect the integrity of junctional complexes. ..
  12. Panneerselvam P, Singh L, Ho B, Chen J, Ding J. Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence. Biochem J. 2012;442:263-71 pubmed publisher
    ..The R14A SARM mutant also showed reduced apoptotic potential when compared with the wild-type. Taken together, S27, which is a bona fide signal sequence that targets SARM to the mitochondria, explains the pro-apoptotic activity of SARM. ..
  13. Onoufriadis A, Shoemark A, Munye M, James C, Schmidts M, Patel M, et al. Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia with defects in the outer dynein arm. J Med Genet. 2014;51:61-7 pubmed publisher
    ..This addition of ARMC4 to the list of genes associated with ciliary outer dynein arm defects expands our understanding of the complexities of PCD genetics. ..
  14. Pai L, Orsulic S, Bejsovec A, Peifer M. Negative regulation of Armadillo, a Wingless effector in Drosophila. Development. 1997;124:2255-66 pubmed
    ..We discuss two models for the negative regulation of Armadillo in normal development and discuss how escape from this regulation contributes to tumorigenesis. ..
  15. Willert K, Logan C, Arora A, Fish M, Nusse R. A Drosophila Axin homolog, Daxin, inhibits Wnt signaling. Development. 1999;126:4165-73 pubmed
    ..The loss-of-function and overexpression phenotypes show that Daxin, like its mammalian counterpart, acts as a negative regulator of wg/Wnt signaling. ..
  16. Pacquelet A, Rørth P. Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion. J Cell Biol. 2005;170:803-12 pubmed
    ..The nature of this additional function is discussed. ..
  17. Hoffmans R, Städeli R, Basler K. Pygopus and legless provide essential transcriptional coactivator functions to armadillo/beta-catenin. Curr Biol. 2005;15:1207-11 pubmed
    ..Our findings therefore indicate that Arm/beta-catenin depends on Lgs and Pygo primarily for its transcriptional output rather than for its nuclear import. ..
  18. Riese J, Yu X, Munnerlyn A, Eresh S, Hsu S, Grosschedl R, et al. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell. 1997;88:777-87 pubmed
    ..Thus, LEF-1 coordinates inputs from multiple positional signals, consistent with its architectural role in regulating the assembly of multiprotein enhancer complexes. ..
  19. Woods D, Wu J, Bryant P. Localization of proteins to the apico-lateral junctions of Drosophila epithelia. Dev Genet. 1997;20:111-8 pubmed
  20. Dumstrei K, Wang F, Shy D, Tepass U, Hartenstein V. Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis. Development. 2002;129:3983-94 pubmed
    ..Finally, EGFR can be co-immunoprecipitated with anti-DE-cadherin and anti-Armadillo antibodies from embryonic protein extracts. We propose that EGFR signaling plays a role in morphogenesis by modulating cell adhesion. ..
  21. Liu C, Li Y, Semenov M, Han C, Baeg G, Tan Y, et al. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002;108:837-47 pubmed
    ..Our study uncovers distinct roles and steps of beta-catenin phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin signaling, and has implications to pathogenesis/therapeutics of human cancers and diabetes. ..
  22. Tolwinski N, Wieschaus E. Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan. Development. 2001;128:2107-17 pubmed
    ..We find that nuclear retention is dependent on dTCF/Pangolin. This suggests that cellular distribution of Arm is controlled by an anchoring system, where various nuclear and cytoplasmic binding partners determine its localization. ..
  23. Hecht A, Litterst C, Huber O, Kemler R. Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro. J Biol Chem. 1999;274:18017-25 pubmed
  24. Aberle H, Schwartz H, Hoschuetzky H, Kemler R. Single amino acid substitutions in proteins of the armadillo gene family abolish their binding to alpha-catenin. J Biol Chem. 1996;271:1520-6 pubmed
    ..Our results indicate that single amino acid mutations in the alpha-catenin binding site of homologs of Armadillo could prevent a stable association with alpha-catenin, thus affecting cadherin-mediated adhesion. ..
  25. Cox R, Kirkpatrick C, Peifer M. Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. J Cell Biol. 1996;134:133-48 pubmed
    ..These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development. ..
  26. Wang T, Chen Y, Hong H, Zeng Y, Zhang J, Lu J, et al. Increased nucleotide polymorphic changes in the 5'-untranslated region of delta-catenin (CTNND2) gene in prostate cancer. Oncogene. 2009;28:555-64 pubmed publisher
    ..This is the first report of delta-catenin gene mutation in cancer and supports the notion that multiple mechanisms contribute to its increased expression in carcinogenesis. ..
  27. Hayward P, Brennan K, Sanders P, Balayo T, DasGupta R, Perrimon N, et al. Notch modulates Wnt signalling by associating with Armadillo/beta-catenin and regulating its transcriptional activity. Development. 2005;132:1819-30 pubmed
    ..The modulatory function of Notch described here, contributes to the establishment of a robust threshold for Wnt signalling which is likely to play important roles in both normal and pathological situations. ..
  28. Sanson B, White P, Vincent J. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature. 1996;383:627-30 pubmed
    ..We demonstrate that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool. ..
  29. Peifer M, Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990;63:1167-76 pubmed
    ..We present a possible model for the cellular role of arm. ..
  30. O Neill L, Bowie A. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353-64 pubmed
    ..These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling. ..
  31. Somorjai I, Martinez Arias A. Wingless signalling alters the levels, subcellular distribution and dynamics of Armadillo and E-cadherin in third instar larval wing imaginal discs. PLoS ONE. 2008;3:e2893 pubmed publisher
    ..Moreover, this study highlights the importance of Armadillo in regulating the subcellular distribution of E-Cadherin. ..
  32. Orsulic S, Peifer M. An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. J Cell Biol. 1996;134:1283-300 pubmed
    ..Finally, we demonstrated that Armadillo's roles in adherens junctions and Wingless signaling are independent. We discuss the potential biochemical role of Armadillo in each process. ..
  33. Cox R, Pai L, Kirkpatrick C, Stein J, Peifer M. Roles of the C terminus of Armadillo in Wingless signaling in Drosophila. Genetics. 1999;153:319-32 pubmed
    ..These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion. ..
  34. Yu X, Waltzer L, Bienz M. A new Drosophila APC homologue associated with adhesive zones of epithelial cells. Nat Cell Biol. 1999;1:144-51 pubmed
  35. Parker D, Jemison J, Cadigan K. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development. 2002;129:2565-76 pubmed
    ..Our data argue strongly that Pygopus is a new core component of the Wg signaling pathway that acts downstream or at the level of TCF. ..
  36. Kim K, Sirota A, Chen Yh Y, Jones S, Dudek R, Lanford G, et al. Dendrite-like process formation and cytoskeletal remodeling regulated by delta-catenin expression. Exp Cell Res. 2002;275:171-84 pubmed
    ..We suggest that delta-catenin can effect a biphasic cytoskeletal remodeling event which differentially regulates actin and microtubules and promotes cellular morphogenesis. ..
  37. Peifer M, Pai L, Casey M. Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. Dev Biol. 1994;166:543-56 pubmed
    ..We discuss the implications of these results for regulation of Wingless/Wnt-1 signaling and adherens junction function. ..
  38. Rocheleau C, Downs W, Lin R, Wittmann C, Bei Y, Cha Y, et al. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell. 1997;90:707-16 pubmed
    ..We present evidence that there may be partially redundant inputs into endoderm specification and that a subset of these genes appear also to function in determining cytoskeletal polarity in certain early blastomeres. ..
  39. Oda H, Uemura T, Shiomi K, Nagafuchi A, Tsukita S, Takeichi M. Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein. J Cell Biol. 1993;121:1133-40 pubmed
    ..These results strongly suggest that Drosophila has a cell adhesion machinery homologous to the vertebrate cadherin-catenin system. ..
  40. Rickelt S, Rizzo S, Doerflinger Y, Zentgraf H, Basso C, Gerosa G, et al. A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata. Mod Pathol. 2010;23:1429-37 pubmed publisher
    ..We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents...
  41. Klingensmith J, Nusse R. Signaling by wingless in Drosophila. Dev Biol. 1994;166:396-414 pubmed
    ..Where appropriate, wingless signaling will be compared to the activity of vertebrate Wnt proteins. ..
  42. Hatzfeld M, Kristjansson G, Plessmann U, Weber K. Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family. J Cell Sci. 1994;107 ( Pt 8):2259-70 pubmed
    ..The amino-terminal region of B6P (residues 1 to 263) shows no significant homology to any known protein sequence. It may therefore be involved in unique functions of B6P. ..
  43. Mink M, Fogelgren B, Olszewski K, Maroy P, Csiszar K. A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans. Genomics. 2001;74:234-44 pubmed
    ..We have identified the same conserved SAM/Armadillo motif combination in the mouse, Drosophila, and Caenorhabditis elegans SARM proteins. ..
  44. Dalod M. Studies of SARM1 uncover similarities between immune and neuronal responses to danger. Sci STKE. 2007;2007:pe73 pubmed
  45. Carty M, Goodbody R, Schröder M, Stack J, Moynagh P, Bowie A. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006;7:1074-81 pubmed
    ..Thus, the fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling. ..
  46. Gallet A, Angelats C, Erkner A, Charroux B, Fasano L, Kerridge S. The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila. EMBO J. 1999;18:2208-17 pubmed
    ..We discuss these results with respect to current models of Armadillo/beta-catenin action for the transmission of the Wingless/Wnt pathway. ..
  47. Ho C, Zhou J, Medina M, Goto T, Jacobson M, Bhide P, et al. delta-catenin is a nervous system-specific adherens junction protein which undergoes dynamic relocalization during development. J Comp Neurol. 2000;420:261-76 pubmed
    ..1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that delta-catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil. ..
  48. Waibler Z, Schafer A, Starzinski Powitz A. mARVCF cellular localisation and binding to cadherins is influenced by the cellular context but not by alternative splicing. J Cell Sci. 2001;114:3873-84 pubmed
    ..Our results suggest that the subcellular localisation of mARVCF may be determined not only by the presence or absence of an appropriate interaction partner, in this case cadherins, but also by the cellular context. ..
  49. Belinda L, Wei W, Hanh B, Lei L, Bow H, Ling D. SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to human. Mol Immunol. 2008;45:1732-42 pubmed
    ..Altogether, our study shows that, although C. elegans SARM upregulates immune signaling, its disparate role as a suppressor of TLR signaling, specifically via TRIF and not MyD88, is well-conserved from horseshoe crab to human. ..
  50. Paffenholz R, Kuhn C, Grund C, Stehr S, Franke W. The arm-repeat protein NPRAP (neurojungin) is a constituent of the plaques of the outer limiting zone in the retina, defining a novel type of adhering junction. Exp Cell Res. 1999;250:452-64 pubmed
    ..This unusual combination of proteins and the demonstrated absence of plakoglobin define the OLZ junctions as a new and distinct category of adhering junction, which probably has special architectural functions. ..
  51. Marygold S, Vincent J. Armadillo levels are reduced during mitosis in Drosophila. Mech Dev. 2003;120:157-65 pubmed
    ..We conclude that this phenomenon may reduce the efficacy of Wingless signalling and/or intercellular adhesion during cell division. ..
  52. Bonne S, van Hengel J, van Roy F. Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily. Genomics. 1998;51:452-4 pubmed
    ..Although some of the Armadillo proteins are highly related to one another, the corresponding genes are dispersed throughout the human genome. ..
  53. Riggleman B, Schedl P, Wieschaus E. Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell. 1990;63:549-60 pubmed
    ..Two other segment polarity genes, porcupine and dishevelled, are required for this effect. We also show that arm protein is closely associated with the plasma membrane in virtually all cell types and often colocalizes with F-actin. ..