Q0VCX4 (CTNB1_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 79. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|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 via BTRC and 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 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. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and SLC30A9. Interacts with XIRP1 and MUC1. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain) and with EMD. Interacts with SCRIB. Interacts with TNIK. Interacts with SESTD1 and TRPC4. 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. Interacts with PKT7. Interacts with FAT1 (via the cytoplasmic domain). Interacts with NANOS1 and NDRG2. Interacts with NEK2, CDK2 and CDK5. Interacts with PTK6. 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. The CTNNB1 and TCF4 complex interacts with PML. Interacts with FERMT2. Identified in a complex with TCF4 and FERMT2. Interacts with RORA. May interact with P-cadherin/CDH3 By similarity. Interacts with RAPGEF2. Ref.3
Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Nucleus By similarity. Cell junction › adherens junction By similarity. Cell junction By similarity. Cell membrane By similarity. 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 and MUC1 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.
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_0000282881|
|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 By similarity|
|||"Characterization of 954 bovine full-CDS cDNA sequences."|
Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.
BMC Genomics 6:166-166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||NIH - Mammalian Gene Collection (MGC) project|
Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal skin.
|||"Identification of a novel beta-catenin-interacting protein."|
Kawajiri A., Itoh N., Fukata M., Nakagawa M., Yamaga M., Iwamatsu A., Kaibuchi K.
Biochem. Biophys. Res. Commun. 273:712-717(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAPGEF2.
|BT030683 mRNA. Translation: ABS44999.1.|
BC119949 mRNA. Translation: AAI19950.1.
|RefSeq||NP_001069609.1. NM_001076141.1. |
3D structure databases
|SMR||Q0VCX4. Positions 19-44, 142-691. |
Protein-protein interaction databases
|IntAct||Q0VCX4. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSBTAT00000021838; ENSBTAP00000021838; ENSBTAG00000016420. |
Family and domain databases
|Gene3D||126.96.36.199. 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: Q0VCX4|
Secondary accession number(s): A7E3R2
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families