Database Accession: DI1000044
Name: Axin RGS-homologous domain in complex with a SAMP repeat from APC
PDB ID: 1emu
Experimental method: X-ray (1.90 Å)
Source organism: Homo sapiens
Proof of disorder:
Primary publication of the structure:
Spink KE, Polakis P, Weis WI
Structural basis of the Axin-adenomatous polyposis coli interaction.
(2000) EMBO J. 19: 2270-9
Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene beta-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3beta (GSK3beta) and several other proteins. Both Axin and APC are known to be critical for beta-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin-APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin-APC complex provide a rationale for the evolutionary conservation seen in both proteins.
ubiquitin protein ligase binding Interacting selectively and non-covalently with a ubiquitin protein ligase enzyme, any of the E3 proteins.
identical protein binding Interacting selectively and non-covalently with an identical protein or proteins.
protein deubiquitination The removal of one or more ubiquitin groups from a protein.
proteasome-mediated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of protein catabolic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
negative regulation of canonical Wnt signaling pathway Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
beta-catenin destruction complex assembly The aggregation, arrangement and bonding together of a set of components to form a beta-catenin destruction complex.
beta-catenin destruction complex disassembly The disaggregation of a beta-catenin destruction complex into its constituent components.
positive regulation of cellular process Any process that activates or increases the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level.
regulation of protein phosphorylation Any process that modulates the frequency, rate or extent of addition of phosphate groups into an amino acid in a protein.
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
cellular response to stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation).
negative regulation of macromolecule metabolic process Any process that decreases the frequency, rate or extent of the chemical reactions and pathways involving macromolecules, any molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass.
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.
lateral plasma membrane The portion of the plasma membrane at the lateral side of the cell. In epithelial cells, lateral plasma membranes are on the sides of cells which lie at the interface of adjacent cells.
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.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
Entry contents: 2 distinct polypeptide molecules
Chains: B, A
Notes: No modifications of the original PDB file.
Name: Adenomatous polyposis coli protein
Source organism: Homo sapiens
Length: 16 residues
Sequence:Sequence according to PDB SEQRESSEDDLLQECISSAMPK
UniProtKB AC: P25054 (positions: 2034-2049)Coverage: 0.6%
UniRef90 AC: UniRef90_P25054 (positions: 2034-2049)
Source organism: Homo sapiens
Length: 132 residues
Sequence:Sequence according to PDB SEQRESPPYLKWAESLHSLLDDQDGISLFRTFLKQEGCADLLDFWFACTGFRKLEPCDSNEEKRLKLARAIYRKYILDNNGIVSRQTKPATKSFIKGCIMKQLIDPAMFDQAQTEIQATMEENTYPSFLKSDIYLEYT
UniProtKB AC: O15169 (positions: 80-211)Coverage: 15.3%
UniRef90 AC: UniRef90_O15169 (positions: 80-211)
The Regulator of G protein signalling (RGS) domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00615). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1zv4.
No related structure was found in the Protein Data Bank.