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beta catenin

Function: - role in the regulation of cell adhesion & in signal transduction through the Wnt pathway - two separate pools are found in the cytoplasm: a) one is PSEN1/cadherin/catenin complex which anchors to the actin cytoskeleton b) the other pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 & GSK3B that promotes phosphorylation on N-terminal Ser & Thr residues & ubiquitination of CTNNB1 via BTRC & its subsequent degradation by the proteasome - Wnt-dependent activation of DVL antagonizes the action of GSK3B - when GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated & is no longer targeted for destruction - the stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9 & possibly also RUVBL1 & DUPLIN - binds CTNNBIP & EP300 - CTNNB1 forms a ternary complex with LEF1 & EP300 that is disrupted by CTNNBIP1 binding - interacts with the PDZ domain of TAX1BP3; this interaction inhibits the transcriptional activity of CTNNB1 - interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR & PCDH11Y. - binds SLC9A3R1 - interacts with GLIS2 & MUC1 interacts with SLC30A9 - interacts with XIRP1 (putative) - phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase (CKIa phosphorylates beta-catenin on Ser-45) - phosphorylation proceeds then from Thr-41 to Ser-37 & Ser-33 - EGF stimulates tyrosine phosphorylation - phosphorylation on Tyr-654 decreases CDH1 binding & enhances TBP binding - ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1A, APC & TBL1X (probable) - ubiquitination leads to its subsequent proteasomal degradation Structure: - belongs to the beta-catenin family - contains 12 ARM repeats Compartment: - cytoplasm, nucleus - cytoplasmic when it is unstabilized (high level of phosphorylation) or bound to CDH1 - translocates to the nucleus when it is stabilized (low level of phosphorylation) - interaction with GLIS2 & MUC1 promotes nuclear translocation Alternative splicing: named isoforms=2 Expression: - expressed in several hair follicle cell types: basal & peripheral matrix cells, & cells of the outer and inner root sheats. - expressed in colon Pathology: - activating mutations in CTNNB1 have oncogenic activity resulting in tumor development - somatic mutations are found in various tumor types, including colon cancers, ovarian cancer & prostate carcinomas, hepatoblastoma, hepatocellular carcinoma - defects in CTNNB1 are a cause of a) pilomatrixoma b) medulloblastoma - chromosomal translocation t(3;8)(p21;q12) involving CTNNB1 with PLAG1 may be a cause of salivary gland pleiomorphic adenomas - mutations &/or accumulation of beta catenin seen in some dedifferentiated liposarcomas & malignant fibrous histiocytomas Laboratory: - beta catenin Ag in tissue

Interactions

molecular events

Related

CTNNB1 gene mutation

General

beta catenin family protein catenin phosphoprotein

Properties

SIZE: entity length = 781 aa MW = 85 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S23} Ser phosphorylation site {S29} Ser phosphorylation site {S33} Ser phosphorylation site {S37} Thr phosphorylation site {T41} Ser phosphorylation site {S45} Tyr phosphorylation site {Y86} ARM repeat {151-191} MOTIF: Ser phosphorylation site {S191} ARM repeat {193-234} ARM repeat {235-276} ARM repeat {277-318} ARM repeat {319-360} ARM repeat {361-389} ARM repeat {400-441} ARM repeat {442-484} ARM repeat {489-530} ARM repeat {531-571} MOTIF: Thr phosphorylation site {T551} Ser phosphorylation site {S552} Thr phosphorylation site {T556} ARM repeat {594-636} ARM repeat {637-666} MOTIF: Tyr phosphorylation site {Y654} Ser phosphorylation site {S675}

References

  1. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002 Mar 22;108(6):837-47. PMID: 11955436
  2. UniProt :accession P35222
  3. Sakamoto A, Oda Y, Adachi T, Saito T, Tamiya S, Iwamoto Y, Tsuneyoshi M. Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma. Arch Pathol Lab Med. 2002 Sep;126(9):1071-8. PMID: 12204056
  4. Atlas of genetics & cytogenetics in oncology & Haematology http://atlasgeneticsoncology.org/genes/CTNNB1ID71.html
  5. Wikipedia, beta-catenin entry http://en.wikipedia.org/wiki/beta-catenin

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 116806 UniProt P35222 PFAM correlations Entrez Gene 1499 Kegg hsa:1499 Figures/diagrams/slides/tables related to beta catenin