Q9WU82 (CTNB1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 126. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||781 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 By similarity. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML By similarity.
Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 Interacts directly with AXIN1; the interaction is regulated by CK2 via BTRC and its subsequent degradation by the proteasome. Interacts directly with AXIN1;the interaction is regulated by CDK2 phosphorylation. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding By similarity. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1 By similarity. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2. Interacts with XIRP1 By similarity. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain) and with SLC30A9. Interacts with EMD By similarity. Interacts with SCRIB By similarity. Interacts with TNIK and TCF7L2 By similarity. Interacts with SESTD1 and TRPC4 By similarity. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. Interacts with PTPRJ By similarity. Interacts with PKT7 By similarity. Interacts with NANOS1 By similarity. Interacts with CDK2, NDRG2, NEK2 and CDK5 By similarity. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with PTK6 By similarity. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT By similarity. The CTNNB1 and TCF4 complex interacts with PML. Interacts with FERMT2. Identified in a complex with TCF4 and FERMT2 By similarity. Interacts with RAPGEF2 By similarity. May interact with P-cadherin/CDH3 By similarity. Interacts with FAT1 (via the cytoplasmic domain). Ref.3 Ref.4 Ref.5
Cytoplasm. Cytoplasm › cytoskeleton. Nucleus. Cell junction › adherens junction By similarity. Cell junction By similarity. Cell membrane. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm › cytoskeleton › spindle pole By similarity. Note: 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 promotes nuclear translocation. Interaction with EMD inhibits nuclear localization. The majority of beta- catenin is localized to the cell membrane. In interphase, colocalizes with CROCC between CEP250 puncta at the proximal end of centrioles, and this localization is dependent on CROCC and CEP250. In mitosis, when NEK2 activity increases, it localizes to centrosomes at spindle poles independent of CROCC. Colocalizes with CDK5 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Colocalized with RAPGEF2 and TJP1 at cell-cell contacts By similarity. Ref.3
Expressed in the testis.
Highly expressed at E30-60 day DPC in the testis. Reduced expression at E90 day DPC.
Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. Phosphorylated on Ser-33 and Ser-37 by HIPK2; this phosphorylation triggers proteasomal degradation. Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription. Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization By similarity. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity By similarity.
Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation. Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation By similarity.
S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions By similarity.
Belongs to the beta-catenin family.
Contains 12 ARM repeats.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 781||780||Catenin beta-1||PRO_0000064273|
|Repeat||151 – 191||41||ARM 1|
|Repeat||193 – 234||42||ARM 2|
|Repeat||235 – 276||42||ARM 3|
|Repeat||277 – 318||42||ARM 4|
|Repeat||319 – 360||42||ARM 5|
|Repeat||361 – 389||29||ARM 6|
|Repeat||400 – 441||42||ARM 7|
|Repeat||442 – 484||43||ARM 8|
|Repeat||489 – 530||42||ARM 9|
|Repeat||531 – 571||41||ARM 10|
|Repeat||594 – 636||43||ARM 11|
|Repeat||637 – 666||30||ARM 12|
|Region||2 – 23||22||Interaction with VCL By similarity|
|Region||156 – 178||23||Interaction with BCL9 By similarity|
|Region||772 – 781||10||Interaction with SCRIB By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||23||1||Phosphoserine; by GSK3-beta By similarity|
|Modified residue||29||1||Phosphoserine; by GSK3-beta By similarity|
|Modified residue||33||1||Phosphoserine; by GSK3-beta and HIPK2 By similarity|
|Modified residue||37||1||Phosphoserine; by GSK3-beta and HIPK2 By similarity|
|Modified residue||41||1||Phosphothreonine; by GSK3-beta By similarity|
|Modified residue||45||1||Phosphoserine By similarity|
|Modified residue||64||1||Phosphotyrosine; by PTK6 By similarity|
|Modified residue||86||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||142||1||Phosphotyrosine; by FYN and PTK6 By similarity|
|Modified residue||191||1||Phosphoserine; by CDK5 By similarity|
|Modified residue||246||1||Phosphoserine; by CDK5 By similarity|
|Modified residue||331||1||Phosphotyrosine By similarity|
|Modified residue||551||1||Phosphothreonine By similarity|
|Modified residue||552||1||Phosphoserine; by AMPK By similarity|
|Modified residue||556||1||Phosphothreonine By similarity|
|Modified residue||619||1||S-nitrosocysteine By similarity|
|Modified residue||654||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||675||1||Phosphoserine Ref.6|
|Sequence conflict||368||1||P → L in AAK85253. Ref.2|
|||"Study on the formation of specialized inter-Sertoli cell junctions in vitro."|
Chung S.S.W., Lee W.M., Cheng C.Y.
J. Cell. Physiol. 181:258-272(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Sequencing of the rat beta-catenin gene (Ctnnb1) and mutational analysis of liver tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline."|
Li Q., Dixon B.M., Al-Fageeh M., Blum C.A., Dashwood R.H.
Gene 283:255-262(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Fischer 344.
|||"The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway."|
Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.
Genes Dev. 20:1933-1945(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH MACF1; APC; AXIN1 AND GSK3B.
|||"The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals."|
Hou R., Liu L., Anees S., Hiroyasu S., Sibinga N.E.
J. Cell Biol. 173:417-429(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAT1.
|||"A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation."|
Sakamoto I., Kishida S., Fukui A., Kishida M., Yamamoto H., Hino S., Michiue T., Takada S., Asashima M., Kikuchi A.
J. Biol. Chem. 275:32871-32878(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHD8.
|||"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."|
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675, MASS SPECTROMETRY.
|+||Additional computationally mapped references.|
|AF121265 mRNA. Translation: AAD28504.1.|
AF397179 Genomic DNA. Translation: AAK85253.1.
|RefSeq||NP_445809.2. NM_053357.2. |
3D structure databases
|SMR||Q9WU82. Positions 19-44, 118-682. |
Protein-protein interaction databases
|IntAct||Q9WU82. 4 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000026016; ENSRNOP00000026016; ENSRNOG00000019139. |
|UCSC||RGD:70487. rat. |
|RGD||70487. Ctnnb1. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.124. 1 hit. |
|InterPro||IPR011989. ARM-like. |
|Pfam||PF00514. Arm. 4 hits. |
|PRINTS||PR01869. BCATNINFAMLY. |
|SMART||SM00185. ARM. 12 hits. |
|SUPFAM||SSF48371. SSF48371. 1 hit. |
|PROSITE||PS50176. ARM_REPEAT. 9 hits. |
|Accession||Primary (citable) accession number: Q9WU82|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families