ID:CTNB1_HUMAN DESCRIPTION: RecName: Full=Catenin beta-1; AltName: Full=Beta-catenin; FUNCTION: 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. SUBUNIT: 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 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 and MUC1. Interacts with SLC30A9. Interacts with XIRP1 (By similarity). Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1 (By similarity). Interacts with SCRIB (By similarity). Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL (By similarity). Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain) (By similarity). Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of 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. INTERACTION: O43707:ACTN4; NbExp=6; IntAct=EBI-491549, EBI-351526; P25054:APC; NbExp=7; IntAct=EBI-491549, EBI-727707; P10275:AR; NbExp=8; IntAct=EBI-491549, EBI-608057; O15169:AXIN1; NbExp=20; IntAct=EBI-491549, EBI-710484; O00512:BCL9; NbExp=2; IntAct=EBI-491549, EBI-533127; P33724:CAV1 (xeno); NbExp=5; IntAct=EBI-491549, EBI-79998; Q6P1J9:CDC73; NbExp=9; IntAct=EBI-491549, EBI-930143; P12830:CDH1; NbExp=6; IntAct=EBI-491549, EBI-727477; P26231:Ctnna1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-647895; Q9NSA3:CTNNBIP1; NbExp=6; IntAct=EBI-491549, EBI-747082; Q9NYF0:DACT1; NbExp=3; IntAct=EBI-491549, EBI-3951744; Q9UKB1:FBXW11; NbExp=2; IntAct=EBI-491549, EBI-355189; Q08050:FOXM1; NbExp=16; IntAct=EBI-491549, EBI-866480; P49841:GSK3B; NbExp=3; IntAct=EBI-491549, EBI-373586; P18012:ipaC (xeno); NbExp=4; IntAct=EBI-491563, EBI-491541; Q14678:KANK1; NbExp=2; IntAct=EBI-491549, EBI-2556221; Q2LD37:KIAA1109; NbExp=2; IntAct=EBI-491549, EBI-2683809; Q8WVC0:LEO1; NbExp=2; IntAct=EBI-491549, EBI-932432; P49768:PSEN1; NbExp=2; IntAct=EBI-491549, EBI-297277; Q13761:RUNX3; NbExp=12; IntAct=EBI-491549, EBI-925990; Q9NQB0:TCF7L2; NbExp=27; IntAct=EBI-491549, EBI-924724; P11388:TOP2A; NbExp=5; IntAct=EBI-491549, EBI-539628; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton. Cell junction, adherens junction. Cell junction. Cell membrane. Cytoplasm, cytoskeleton, centrosome. Cytoplasm, cytoskeleton, spindle pole. 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. Co-localizes with CDK5 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. TISSUE SPECIFICITY: Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). PTM: Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription (By similarity). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and 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 on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. 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. PTM: 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). DISEASE: Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:114500]. DISEASE: Note=Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. DISEASE: Defects in CTNNB1 are a cause of pilomatrixoma (PTR) [MIM:132600]; a common benign skin tumor. DISEASE: Defects in CTNNB1 are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. DISEASE: Defects in CTNNB1 are a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late- stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. DISEASE: Note=A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1. DISEASE: Defects in CTNNB1 may be a cause of mesothelioma malignant (MESOM) [MIM:156240]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. SIMILARITY: Belongs to the beta-catenin family. SIMILARITY: Contains 12 ARM repeats. SEQUENCE CAUTION: Sequence=BAB93475.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CTNNB1ID71.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ctnnb1/"; WEB RESOURCE: Name=Wikipedia; Note=Beta-catenin entry; URL="http://en.wikipedia.org/wiki/Beta-catenin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P35222
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK289932 - Homo sapiens cDNA FLJ78465 complete cds, highly similar to Homo sapiens catenin (cadherin-associated protein), beta 1, 88kDa (CTNNB1), mRNA. AK294778 - Homo sapiens cDNA FLJ57878 complete cds, highly similar to Beta-catenin. AK314776 - Homo sapiens cDNA, FLJ95646. AK296790 - Homo sapiens cDNA FLJ59565 complete cds, highly similar to Beta-catenin. X87838 - H.sapiens mRNA for beta-catenin. Z19054 - H.sapiens of beta catenin gene. BC058926 - Homo sapiens catenin (cadherin-associated protein), beta 1, 88kDa, mRNA (cDNA clone MGC:65131 IMAGE:6151332), complete cds. JD191319 - Sequence 172343 from Patent EP1572962. AK299954 - Homo sapiens cDNA FLJ59415 complete cds, highly similar to Beta-catenin. JD441660 - Sequence 422684 from Patent EP1572962. JD078805 - Sequence 59829 from Patent EP1572962. JD443803 - Sequence 424827 from Patent EP1572962. AB451392 - Homo sapiens CTNNB1 mRNA for catenin beta-1, partial cds, clone: FLJ08084AAAF. AB463467 - Synthetic construct DNA, clone: pF1KB6277, Homo sapiens CTNNB1 gene for catenin (cadherin-associated protein) beta 1, without stop codon, in Flexi system. EU446854 - Synthetic construct Homo sapiens clone IMAGE:100070227; IMAGE:100012063; FLH258229.01L catenin (cadherin-associated protein), beta 1, 88kDa (CTNNB1) gene, encodes complete protein. AB451264 - Homo sapiens CTNNB1 mRNA for catenin beta-1, complete cds, clone: FLJ08084AAAN. AB062292 - Homo sapiens OK/SW-cl.35 mRNA for catenin beta 1, complete cds. AK098472 - Homo sapiens cDNA FLJ25606 fis, clone JTH14532, highly similar to BETA-CATENIN. BX648430 - Homo sapiens mRNA; cDNA DKFZp686D02253 (from clone DKFZp686D02253). JD026789 - Sequence 7813 from Patent EP1572962. AK095242 - Homo sapiens cDNA FLJ37923 fis, clone CTONG1000283, weakly similar to BETA-CATENIN. JD020993 - Sequence 2017 from Patent EP1572962. JD024298 - Sequence 5322 from Patent EP1572962. JD036195 - Sequence 17219 from Patent EP1572962. JD023311 - Sequence 4335 from Patent EP1572962. JD032519 - Sequence 13543 from Patent EP1572962. JD027033 - Sequence 8057 from Patent EP1572962. JD348564 - Sequence 329588 from Patent EP1572962. JD170773 - Sequence 151797 from Patent EP1572962. JD237640 - Sequence 218664 from Patent EP1572962. JD504200 - Sequence 485224 from Patent EP1572962. U38440 - Human clone JkA11 mRNA induced upon T-cell activation, 3' end. MP095949 - Sequence 1 from Patent EP3436582. LY641411 - KR 1020180124142-A/1963: NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF. MB124127 - JP 2019513371-A/1963: NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_cell2cellPathway - Cell to Cell Adhesion Signaling h_pitx2Pathway - Multi-step Regulation of Transcription by Pitx2 h_alkPathway - ALK in cardiac myocytes h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages h_ps1Pathway - Presenilin action in Notch and Wnt signaling h_wntPathway - WNT Signaling Pathway h_tffPathway - Trefoil Factors Initiate Mucosal Healing
Reactome (by CSHL, EBI, and GO)
Protein P35222 (Reactome details) participates in the following event(s):
R-HSA-202969 Caspase mediated cleavage of beta-catenin R-HSA-195304 Association of beta-catenin with the destruction complex R-HSA-3134901 LRR FLII-interacting protein 1 associates with beta-catenin R-HSA-201685 Beta-catenin is released from the destruction complex R-HSA-3134883 Beta-catenin enhances association of IRF3 with CBP/p300 R-HSA-3134904 Phosphorylation of beta-catenin at Ser552 R-HSA-3299569 Beta-catenin displaces TLE:HDAC1 from TCF/LEF R-HSA-3769383 CBY1 binds beta-catenin R-HSA-3772430 CTNNBIP1 binds beta-catenin R-HSA-5368580 CHD8 binds beta-catenin to negatively regulate WNT-dependent gene expression R-HSA-5626938 Beta-catenin binds SOX proteins R-HSA-5672304 IQGAP1 binds CDH1:CTTNB1:CTTNA1 and MEN1 R-HSA-195318 Phosphorylation of beta-catenin at Ser45 by CK1 alpha R-HSA-8876497 InlA binds CDH1 R-HSA-3364014 Recruitment of SET1 methyltransferase complex R-HSA-201712 Beta-catenin:TCF associates with BCL9 and PYGO R-HSA-3322422 Beta-catenin recruits SMARCA4 R-HSA-3322424 Beta-catenin recruits CDC73 and LEO1 R-HSA-3322427 Beta-catenin recruits CBP/p300 R-HSA-3451153 Beta-catenin recruits TRRAP/KAT5 HAT components R-HSA-5665608 TCF:Beta-catenin binds SOX proteins R-HSA-8944362 TCF/LEF:CTNNB1 bind canonical WNT target promoters R-HSA-3769393 YWHAZ binds p-CBY:CTNNB1 R-HSA-3769394 AKT phosphorylates CBY1 R-HSA-4411367 TCF7L1/TCF7L2/LEF1:CTNNB1 bind the MYC gene R-HSA-4411383 NLK phosphorylates TCF/LEF R-HSA-4411351 TCF/LEF:CTNNB1 bind the AXIN2 gene R-HSA-8951428 RUNX3 binds CTNNB1:TCF7L2,(LEF1,TCF7L1,TCF7) R-HSA-8951442 CTNNB1:TCF7L2,LEF1 binds the CCND1 gene promoter R-HSA-8876993 CBLL1 binds SRC-phosphorylated CDH1 complex R-HSA-195287 Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3 R-HSA-195283 Phosphorylation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3 R-HSA-195300 Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3 R-HSA-195275 Phosphorylation of APC component of the destruction complex R-HSA-195280 Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex R-HSA-2130279 Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex R-HSA-3364026 SET1 complex trimethylates H3K4 at the MYC gene R-NUL-3451144 KAT5 HAT complex acetylates TCF4 (ITF-2) gene at histone H4 R-HSA-3769391 XPO1 binds the beta-catenin:CBY complex R-HSA-8877003 CBLL1 ubiqutinates the InlA-bound CDH1 complex R-HSA-2130286 Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1) R-HSA-419002 Interaction of cadherin with Beta/gamma catenin, alpha catenin and p120 catenin R-HSA-375140 CDO binds promyogenic cadherins R-HSA-3451147 KAT5 HAT complex acetylates TCF4 gene at histone H4 R-HSA-5357477 PAK1-3 phosphorylates VE-cadherin R-HSA-376121 Bnip2 interacts with CDO complex R-HSA-376119 Interaction of Bnip-2 with Cdc42 R-HSA-376117 JLP interacts with CDO complex R-HSA-449200 Interaction of ABL1 with CDO complex R-HSA-448957 Interaction of p38 MAPK with JLP R-HSA-351906 Apoptotic cleavage of cell adhesion proteins R-HSA-195253 Degradation of beta-catenin by the destruction complex R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-3134973 LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex R-HSA-3769402 Deactivation of the beta-catenin transactivating complex R-HSA-111465 Apoptotic cleavage of cellular proteins R-HSA-5626467 RHO GTPases activate IQGAPs R-HSA-196299 Beta-catenin phosphorylation cascade R-HSA-8876493 InlA-mediated entry of Listeria monocytogenes into host cells R-HSA-195721 Signaling by WNT R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-4086398 Ca2+ pathway R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters R-HSA-8951430 RUNX3 regulates WNT signaling R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin R-HSA-75153 Apoptotic execution phase R-HSA-195258 RHO GTPase Effectors R-HSA-8876384 Listeria monocytogenes entry into host cells R-HSA-162582 Signal Transduction R-HSA-168249 Innate Immune System R-HSA-3858494 Beta-catenin independent WNT signaling R-HSA-8878159 Transcriptional regulation by RUNX3 R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated R-HSA-4791275 Signaling by WNT in cancer R-HSA-418990 Adherens junctions interactions R-HSA-109581 Apoptosis R-HSA-194315 Signaling by Rho GTPases R-HSA-5663205 Infectious disease R-HSA-375170 CDO in myogenesis R-HSA-168256 Immune System R-HSA-212436 Generic Transcription Pathway R-HSA-4839743 phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex R-HSA-5663202 Diseases of signal transduction R-HSA-5218920 VEGFR2 mediated vascular permeability R-HSA-421270 Cell-cell junction organization R-HSA-5357801 Programmed Cell Death R-HSA-1643685 Disease R-HSA-525793 Myogenesis R-HSA-73857 RNA Polymerase II Transcription R-HSA-4420097 VEGFA-VEGFR2 Pathway R-HSA-446728 Cell junction organization R-HSA-1266738 Developmental Biology R-HSA-74160 Gene expression (Transcription) R-HSA-194138 Signaling by VEGF R-HSA-1500931 Cell-Cell communication R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
