The domain within your query sequence starts at position 591 and ends at position 633; the E-value for the ARM domain shown below is 8e-20.

SPARGYELLFQPEVVRIYISLLKESKTPAILEASAGAIQNLCA

The domain was found using the schnipsel database

ARM

Armadillo/beta-catenin-like repeats

• 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)

There are 167287 ARM domains in 29030 proteins in SMART's nrdb database.

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

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

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

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

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

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

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

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	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
3wpt	3WPT
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
4d49	4D49
4d4e	4D4E
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
4plq	4PLQ
4plr	4PLR
4pls	4PLS
4pvz	4PVZ
4r0z	4R0Z
4r10	4R10
4r11	4R11
4rv1	4RV1
4rxh	4RXH
4rzp	4RZP
4tnm	4TNM
4u2x	4U2X
4u54	4U54
4u58	4U58
4u5l	4U5L
4u5n	4U5N
4u5o	4U5O
4u5s	4U5S
4u5u	4U5U
4u5v	4U5V
4uad	4UAD
4uae	4UAE
4uaf	4UAF
4v3o	4V3O
4v3q	4V3Q
4v3r	4V3R
4wv6	4WV6
4xl5	4XL5
4xzr	4XZR
4yi0	4YI0
4yje	4YJE
4yjl	4YJL
4yk6	4YK6
4zdu	4ZDU
4zv6	4ZV6
5aei	5AEI
5b56	5B56
5ctt	5CTT
5d5k	5D5K
5e6q	5E6Q
5ekf	5EKF
5ekg	5EKG
5fc8	5FC8
5hhg	5HHG
5huw	5HUW
5huy	5HUY
5k9s	5K9S
5klr	5KLR
5klt	5KLT
5svz	5SVZ

Links (links to other resources describing this domain)

• PFAM: Armadillo_seg
• INTERPRO: IPR000225