General Information

Database Accession: DI1010051

Name: Beta-catenin armadillo repeat domain bound to ICAT

PDB ID: 1m1e PDB

Experimental method: X-ray (2.10 Å)

Source organism: Homo sapiens / Mus musculus

Proof of disorder: Confirmed

K_d: 3.10×10^-09 M PubMed

Primary publication of the structure:

Daniels DL, Weis WI
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
(2002) Mol. Cell 10: 573-84

PMID: 12408825 PubMed

Abstract:

In the canonical Wnt signaling pathway, beta-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators. The crystal structure of ICAT, an inhibitor of beta-catenin-mediated transcription, bound to the armadillo repeat domain of beta-catenin, has been determined. ICAT contains an N-terminal helilical domain that binds to repeats 11 and 12 of beta-catenin, and an extended C-terminal region that binds to repeats 5-10 in a manner similar to that of Tcfs and other beta-catenin ligands. Full-length ICAT dissociates complexes of beta-catenin, Lef-1, and the transcriptional coactivator p300, whereas the helical domain alone selectively blocks binding to p300. The C-terminal armadillo repeats of beta-catenin may be an attractive target for compounds designed to disrupt aberrant beta-catenin-mediated transcription associated with various cancers.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

protein domain specific binding Interacting selectively and non-covalently with a specific domain of a protein. GeneOntology

Biological process:

negative regulation of transcription from RNA polymerase II promoter Any process that stops, prevents, or reduces the frequency, rate or extent of transcription from an RNA polymerase II promoter. GeneOntology

branching involved in ureteric bud morphogenesis The process in which the branching structure of the ureteric bud is generated and organized. The ureteric bud is an epithelial tube that grows out from the metanephric duct. The bud elongates and branches to give rise to the ureter and kidney collecting tubules. GeneOntology

Wnt signaling pathway The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state. GeneOntology

positive regulation of osteoblast differentiation Any process that activates or increases the frequency, rate or extent of osteoblast differentiation. GeneOntology

regulation of mesenchymal cell proliferation Any process that modulates the frequency, rate or extent of mesenchymal cell proliferation. A mesenchymal cell is a cell that normally gives rise to other cells that are organized as three-dimensional masses, rather than sheets. GeneOntology

negative regulation of cell proliferation Any process that stops, prevents or reduces the rate or extent of cell proliferation. GeneOntology

anterior/posterior pattern specification The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism. GeneOntology

regulation of myeloid leukocyte differentiation Any process that modulates the frequency, rate, or extent of myeloid leukocyte differentiation. GeneOntology

regulation of smooth muscle cell proliferation Any process that modulates the frequency, rate or extent of smooth muscle cell proliferation. GeneOntology

regulation of DNA binding Any process that modulates the frequency, rate or extent of DNA binding. DNA binding is any process in which a gene product interacts selectively with DNA (deoxyribonucleic acid). GeneOntology

regulation of protein complex assembly Any process that modulates the frequency, rate or extent of protein complex assembly. GeneOntology

negative regulation of signal transduction Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction. GeneOntology

Cellular component:

nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. GeneOntology

cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GeneOntology

beta-catenin destruction complex A cytoplasmic protein complex containing glycogen synthase kinase-3-beta (GSK-3-beta), the adenomatous polyposis coli protein (APC), and the scaffolding protein axin, among others; phosphorylates beta-catenin, targets it for degradation by the proteasome. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: B, A

Notes: No modifications of the original PDB file.

Chain B

Name: Beta-catenin-interacting protein 1 Disordered Confirmed

Source organism: Homo sapiens

Length: 81 residues

Sequence:Sequence according to PDB SEQRESMNREGAPGKSPEEMYIQQKVRVLLMLRKMGSNLTASEEEFLRTYAGVVNSQLSQLPPHSIDQGAEDVVMAFSRSETEDRRQ

UniProtKB AC: Q9NSA3 (positions: 1-81) UniProt Coverage: 100%

UniRef90 AC: UniRef90_Q9NSA3 (positions: 1-81) UniRef90

Chain A

Name: Catenin beta-1 Ordered

Source organism: Mus musculus

Length: 538 residues

Sequence:Sequence according to PDB SEQRESHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYK

UniProtKB AC: Q02248 (positions: 134-671) UniProt Coverage: 68.9%

UniRef90 AC: UniRef90_Q02248 (positions: 134-671) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain B: Disordered Confirmed

ICAT consists of two regions that interact directly with beta-catenin, a helical N-terminal domain and an extended acidic C-terminal region that are connected by a flexible tether. It is shown that, unlike cadherins, Tcf-4 and APC, ICAT contains some folded structure in the absence of beta-catenin (PMID: 12408825)

Chain A: Ordered

The armadillo repeat domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00514). A solved monomeric structure of the domain is represented by PDB ID 2bct.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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