|SMART accession number:||SM00185|
|Description:||Approx. 40 amino acid repeat. Tandem repeats form superhelix of helices that is proposed to mediate interaction of beta-catenin with its ligands. Involved in transducing the Wingless/Wnt signal. In plakoglobin arm repeats bind alpha-catenin and N-cadherin.|
|Interpro abstract (IPR000225):|
The armadillo (Arm) repeat is an approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila melanogaster segment polarity gene armadillo involved in signal transduction through wingless. Animal Arm-repeat proteins function in various processes, including intracellular signalling and cytoskeletal regulation, and include such proteins as beta-catenin, the junctional plaque protein plakoglobin, the adenomatous polyposis coli (APC) tumour suppressor protein, and the nuclear transport factor importin-alpha, amongst others [(PUBMED:9770300)]. A subset of these proteins is conserved across eukaryotic kingdoms. In higher plants, some Arm-repeat proteins function in intracellular signalling like their mammalian counterparts, while others have novel functions [(PUBMED:12946625)].
The 3-dimensional fold of an armadillo repeat is known from the crystal structure of beta-catenin, where the 12 repeats form a superhelix of alpha helices with three helices per unit [(PUBMED:9298899)]. The cylindrical structure features a positively charged grove, which presumably interacts with the acidic surfaces of the known interaction partners of beta-catenin.
|GO function:||protein binding (GO:0005515)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing ARM domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with ARM domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing ARM domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Binding / catalysis: protein-binding
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Cavallo R, Rubenstein D, Peifer M
- Armadillo and dTCF: a marriage made in the nucleus.
- Curr Opin Genet Dev. 1997; 7: 459-66
- Display abstract
Within the past year, Armadillo and beta-catenin's role in transducing the Wingless/Wnt signal has been substantially clarified. It is now clear that Armadillo and beta-catenin bind directly to members of the T-cell factor/lymphoid enhancer factor subfamily of HMG box DNA-binding proteins, forming bipartite transcription factors that regulate Wingless/Wnt responsive genes in both Drosophila and vertebrates. These partners not only play key roles in a variety of cell fate decisions during normal development but, when inappropriately activated, contribute to both colon cancer and melanoma.
- Huber AH, Nelson WJ, Weis WI
- Three-dimensional structure of the armadillo repeat region of beta-catenin.
- Cell. 1997; 90: 871-82
- Display abstract
Beta-catenin is essential for cadherin-based cell adhesion and Wnt/Wingless growth factor signaling. In these roles, it binds to cadherins, Tcf-family transcription factors, and the tumor suppressor gene product Adenomatous Polyposis Coli (APC). A core region of beta-catenin, composed of 12 copies of a 42 amino acid sequence motif known as an armadillo repeat, mediates these interactions. The three-dimensional structure of a protease-resistant fragment of beta-catenin containing the armadillo repeat region has been determined. The 12 repeats form a superhelix of helices that features a long, positively charged groove. Although unrelated in sequence, the beta-catenin binding regions of cadherins, Tcfs, and APC are acidic and are proposed to interact with this groove.
- Gumbiner BM
- Signal transduction of beta-catenin.
- Curr Opin Cell Biol. 1995; 7: 634-40
- Display abstract
Beta-catenin participates in signal transduction and developmental patterning in Xenopus and Drosophila embryos as a component of the Wnt signaling pathway. Its signaling activity is distinct from its role in cadherin-mediated cell adhesion, and it probably acts either in the cytosol or in the nucleus. The adenomatous polyposis coli tumor suppressor protein is also implicated in beta-catenin signaling.
- Sacco PA, McGranahan TM, Wheelock MJ, Johnson KR
- Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin.
- J Biol Chem. 1995; 270: 20201-6
- Display abstract
Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule must be associated with the cytoskeleton via cytoplasmic proteins known as catenins. Three catenins, alpha-catenin, beta-catenin, and gamma-catenin (also known as plakoglobin), have been identified. The domain of the cadherin molecule important for its interaction with the catenins has been mapped to the COOH-terminal 70 amino acids, but less is known about regions of the catenins that allow them to associate with one another or with the cadherin molecule. In this study we have transfected carboxyl-terminal deletions of plakoglobin into the human fibrosarcoma HT-1080 and used immunofluorescence localization and co-immunoprecipitation to map the regions of plakoglobin that allow it to associate with N-cadherin and with alpha-catenin. Plakoglobin is an armadillo family member containing 13 weakly similar internal repeats. These data show that the alpha-catenin-binding region maps within the first repeat and the N-cadherin-binding region maps within repeats 7 and 8.
- Rubinfeld B et al.
- Association of the APC gene product with beta-catenin.
- Science. 1993; 262: 1731-4
- Display abstract
Mutations in the human APC gene are linked to familial adenomatous polyposis and to the progression of sporadic colorectal and gastric tumors. To gain insight into APC function, APC-associated proteins were identified by immunoprecipitation experiments. Antibodies to APC precipitated a 95-kilodalton protein that was purified and identified by sequencing as beta-catenin, a protein that binds to the cell adhesion molecule E-cadherin. An antibody specific to beta-catenin also recognized the 95-kilodalton protein in the immunoprecipitates. These results suggest that APC is involved in cell adhesion.
- Su LK, Vogelstein B, Kinzler KW
- Association of the APC tumor suppressor protein with catenins.
- Science. 1993; 262: 1734-7
- Display abstract
Mutations of APC appear to initiate sporadic and inherited forms of human colorectal cancer. Although these mutations have been well characterized, little is known about the function of the APC gene product. Two cellular proteins that associate with APC were identified by nucleotide sequence analysis and peptide mapping as the E-cadherin-associated proteins alpha- and beta-catenin. A 27-residue fragment of APC containing a 15-amino acid repeat was sufficient for the interaction with the catenins. These results suggest an important link between tumor initiation and cell adhesion.
- 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
- Display abstract
The Drosophila segment polarity gene armadillo is required for pattern formation within embryonic segments and imaginal discs. We have found that armadillo is highly conserved during evolution; it is 63% identical to human plakoglobin, a protein found in adhesive junctions joining epithelial and other cells. We have examined arm protein localization in a number of larval tissues and found that arm protein accumulation within cells shares many features with the accumulation of plakoglobin. We have compared the phenotype and molecular lesions responsible for the different arm mutations. Surprisingly, severely truncated proteins retain some function; the degree of function is strictly correlated with the length of the truncated protein, suggesting that the internally repetitive arm protein is modular in function. We present a possible model for the cellular role of arm.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 12.22 map05217 Basal cell carcinoma 11.76 map05210 Colorectal cancer 11.76 map04310 Wnt signaling pathway 11.76 map05213 Endometrial cancer 7.69 map04520 Adherens junction 7.69 map04670 Leukocyte transendothelial migration 7.24 map04810 Regulation of actin cytoskeleton 4.52 map05216 Thyroid cancer 4.52 map04530 Tight junction 4.52 map04916 Melanogenesis 4.52 map04510 Focal adhesion 4.52 map05215 Prostate cancer 3.62 map05221 Acute myeloid leukemia 3.17 map04140 Regulation of autophagy 0.45 map04340 Hedgehog signaling pathway
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with ARM domain which could be assigned to a KEGG orthologous group, and not all proteins containing ARM domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of ARM domains in PDB
PDB code Main view Title 1bk5 KARYOPHERIN ALPHA FROM SACCHAROMYCES CEREVISIAE 1bk6 KARYOPHERIN ALPHA (YEAST) + SV40 T ANTIGEN NLS 1ee4 CRYSTAL STRUCTURE OF YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A C-MYC NLS PEPTIDE 1ee5 YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A NUCLEOPLASMIN NLS PEPTIDE 1ejl MOUSE IMPORTIN ALPHA-SV40 LARGE T ANTIGEN NLS PEPTIDE COMPLEX 1ejy MOUSE IMPORTIN ALPHA-NUCLEOPLASMIN NLS PEPTIDE COMPLEX 1g3j CRYSTAL STRUCTURE OF THE XTCF3-CBD/BETA-CATENIN ARMADILLO REPEAT COMPLEX 1i7w BETA-CATENIN/PHOSPHORYLATED E-CADHERIN COMPLEX 1i7x BETA-CATENIN/E-CADHERIN COMPLEX 1ial IMPORTIN ALPHA, MOUSE 1iq1 CRYSTAL STRUCTURE OF THE IMPORTIN-ALPHA(44-54)-IMPORTIN-ALPHA(70-529) COMPLEX 1jdh CRYSTAL STRUCTURE OF BETA-CATENIN AND HTCF-4 1jpp The Structure of a beta-Catenin Binding Repeat from Adenomatous Polyposis Coli (APC) in Complex with beta-Catenin 1jpw Crystal Structure of a Human Tcf-4 / beta-Catenin Complex 1luj Crystal Structure of the Beta-catenin/ICAT Complex 1m1e Beta-catenin armadillo repeat domain bound to ICAT 1pjm Mouse Importin alpha-bipartite NLS from human retinoblastoma protein Complex 1pjn Mouse Importin alpha-bipartite NLS N1N2 from Xenopus laevis phosphoprotein Complex 1q1s Mouse Importin alpha- phosphorylated SV40 CN peptide complex 1q1t Mouse Importin alpha: non-phosphorylated SV40 CN peptide complex 1qz7 Beta-catenin binding domain of Axin in complex with beta-catenin 1t08 Crystal structure of beta-catenin/ICAT helical domain/unphosphorylated APC R3 1th1 Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment 1un0 Crystal Structure of Yeast Karyopherin (Importin) alpha in complex with a Nup2p N-terminal fragment 1v18 The crystal structure of beta-catenin armadillo repeat complexed with a phosphorylated APC 20mer repeat. 1wa5 Crystal structure of the exportin Cse1p complexed with its cargo ( Kap60p) and RanGTP 1xm9 Structure of the armadillo repeat domain of plakophilin 1 1y2a Structure of mammalian importin bound to the non-classical PLSCR1-NLS 2bct THE ARMADILLO REPEAT REGION FROM MURINE BETA-CATENIN 2c1m Nup50:importin-alpha complex 2c1t Structure of the Kap60p:Nup2 complex 2gl7 Crystal Structure of a beta-catenin/BCL9/Tcf4 complex 2jdq C-terminal domain of influenza A virus polymerase PB2 subunit in complex with human importin alpha5 2ynr mImp_alphadIBB_B54NLS 2yns rImp_alpha_B54NLS 2z6g Crystal Structure of a Full-Length Zebrafish Beta-Catenin 2z6h Crystal Structure of Beta-Catenin Armadillo Repeat Region and Its C-Terminal domain 3au3 Crystal structure of armadillo repeat domain of APC 3bct THE ARMADILLO REPEAT REGION FROM MURINE BETA-CATENIN 3btr AR-NLS:Importin-alpha complex 3fex Crystal structure of the CBC-importin alpha complex. 3fey Crystal structure of the CBC-importin alpha complex. 3ifq Interction of plakoglobin and beta-catenin with desmosomal cadherins 3knd TPX2:importin-alpha complex 3l3q Mouse importin alpha-pepTM NLS peptide complex 3l6x Crystal structure of p120 catenin in complex with E-cadherin 3l6y Crystal structure of p120 catenin in complex with E-cadherin 3nmw Crytal structure of armadillo repeats domain of APC 3nmx Crystal structure of APC complexed with Asef 3nmz Crytal structure of APC complexed with Asef 3now UNC-45 from Drosophila melanogaster 3oqs Crystal structure of importin-alpha bound to a CLIC4 NLS peptide 3ouw Structure of beta-catenin with Lef-1 3oux Structure of beta-catenin with phosphorylated Lef-1 3q5u A minimal NLS from human scramblase 4 complexed with importin alpha 3qhe Crystal structure of the complex between the armadillo repeat domain of adenomatous polyposis coli and the tyrosine-rich domain of Sam68 3rz9 Mouse importin alpha-Ku80 NLS peptide complex 3rzx Mouse importin alpha-Ku70 NLS peptide complex 3sl9 X-ray structure of Beta catenin in complex with Bcl9 3sla X-ray structure of first four repeats of human beta-catenin 3t7u A NeW Crytal structure of APC-ARM 3tj3 Structure of importin a5 bound to the N-terminus of Nup50 3tpm Crystal structure of MAL RPEL domain in complex with importin-alpha 3tpo Crystal structure of D192A/E396A mutant of mouse importin alpha2 3tt9 Crystal structure of the stable degradation fragment of human plakophilin 2 isoform a (PKP2a) C752R variant 3tx7 Crystal structure of LRH-1/beta-catenin complex 3ukw Mouse importin alpha: Bimax1 peptide complex 3ukx Mouse importin alpha: Bimax2 peptide complex 3uky Mouse importin alpha: yeast CBP80 cNLS complex 3ukz Mouse importin alpha: mouse CBP80 cNLS complex 3ul0 Mouse importin alpha: mouse CBP80Y8D cNLS complex 3ul1 Mouse importin alpha: nucleoplasmin cNLS peptide complex 3uvu Structural basis of nuclear import of Flap endonuclease 1 (FEN1) 3ve6 Crystal Structure Analysis of Venezuelan Equine Encephalitis Virus Capsid Protein NLS and Importin Alpha 3zin Gu_alpha_helicase 3zio minor-site specific NLS (A28) 3zip minor-site specific NLS (A58) 3ziq minor-site specific NLS (B6) 3zir minor-site specific NLS (B141) 4b18 The crystal structure of human Importin alpha 5 with TERT NLS peptide 4b8j rImp_alpha1a 4b8o rImp_alpha_SV40TAgNLS 4b8p rImp_alpha_A89NLS 4ba3 mImp_alphadIBB_A89NLS 4bpl rice importin_alpha in complex with nucleoplasmin NLS 4bqk rice importin_alpha : VirD2NLS complex 4db6 Designed Armadillo repeat protein (YIIIM3AII) 4db8 Designed Armadillo-repeat Protein 4db9 Designed Armadillo repeat protein (YIIIM3AIII) 4dba Designed Armadillo repeat protein (YIIM3AII) 4djs Structure of beta-catenin in complex with a stapled peptide inhibitor 4e4v The crystal structure of the dimeric human importin alpha 1 at 2.5 angstrom resolution. 4ev8 Crystal structure of mouse catenin beta-59 in 2.4M urea. 4ev9 Crystal Structure of Mouse Catenin beta-59 in 4.0M urea 4eva Crystal Structure of Mouse Catenin beta-59 in 5.6M urea 4evp Crystal Structure of Mouse Catenin beta-59 in 7.2M urea 4evt Crystal Structure of Mouse Catenin beta-59 in 8.3M urea 4htv Mouse importin alpha: BFDV Cap NLS peptide complex 4hxt Crystal Structure of Engineered Protein. Northeast Structural Genomics Consortium Target OR329 4mz5 Structure of importin-alpha: dUTPase NLS complex 4mz6 Structure of importin-alpha: dUTPase S11E NLS mutant complex 4oih Importin Alpha in Complex with the Bipartite NLS of Prp20
- Links (links to other resources describing this domain)
PFAM Armadillo_seg INTERPRO IPR000225