InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CTNNB1

Summary

InnateDB Protein

IDBP-238035.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CTNNB1

Protein Name

catenin (cadherin-associated protein), beta 1, 88kDa

Synonyms

armadillo; CTNNB; MRD19;

Species

Homo sapiens

Ensembl Protein

ENSP00000379486

InnateDB Gene

IDBG-27347 (CTNNB1)

Protein Structure

UniProt Annotation

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. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. {ECO:0000269PubMed:17524503, ECO:0000269PubMed:18077326, ECO:0000269PubMed:18086858, ECO:0000269PubMed:18957423, ECO:0000269PubMed:21262353, ECO:0000269PubMed:22155184, ECO:0000269PubMed:22647378, ECO:0000269PubMed:22699938}.

Subcellular Localization

Cytoplasm. Nucleus. Cytoplasm, cytoskeleton. Cell junction, adherens junction. Cell junction. Cell membrane. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Note=Colocalized with RAPGEF2 and TJP1 at cell-cell contacts (By similarity). 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. {ECO:0000250}.

Disease Associations

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269PubMed:9065402}. Note=The gene represented in this entry may be involved in disease pathogenesis.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.Pilomatrixoma (PTR) [MIM:132600]: Common benign skin tumor. {ECO:0000269PubMed:10192393, ECO:0000269PubMed:11703283}. Note=The disease is caused by mutations affecting the gene represented in this entry.Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. {ECO:0000269PubMed:10666372}. Note=The gene represented in this entry may be involved in disease pathogenesis.Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors 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. {ECO:0000269PubMed:10391090}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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.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. {ECO:0000269PubMed:11464291}. Note=The gene represented in this entry may be involved in disease pathogenesis.Mental retardation, autosomal dominant 19 (MRD19) [MIM:615075]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD19 features include severe intellectual disability with absent or very limited speech, microcephaly, and spasticity which severely impaired the ability to walk. {ECO:0000269PubMed:23033978}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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). {ECO:0000269PubMed:11703283, ECO:0000269PubMed:17009320, ECO:0000269PubMed:17289029}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 603 experimentally validated interaction(s) in this database.
They are also associated with 106 interaction(s) predicted by orthology.

Experimentally validated
Total	603 [view]
Protein-Protein	554 [view]
Protein-DNA	38 [view]
Protein-RNA	0
DNA-DNA	11 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	106 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001102	RNA polymerase II activating transcription factor binding
GO:0003713	transcription coactivator activity
GO:0004871	signal transducer activity
GO:0005198	structural molecule activity
GO:0005488	binding
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding
GO:0019900	kinase binding
GO:0019901	protein kinase binding
GO:0019903	protein phosphatase binding
GO:0030331	estrogen receptor binding
GO:0035257	nuclear hormone receptor binding
GO:0044212	transcription regulatory region DNA binding
GO:0044325	ion channel binding
GO:0045294	alpha-catenin binding
GO:0045296	cadherin binding
GO:0046332	SMAD binding
GO:0050681	androgen receptor binding
GO:0070411	I-SMAD binding
GO:0070412	R-SMAD binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000578	embryonic axis specification
GO:0001569	patterning of blood vessels
GO:0001658	branching involved in ureteric bud morphogenesis
GO:0001702	gastrulation with mouth forming second
GO:0001711	endodermal cell fate commitment
GO:0001837	epithelial to mesenchymal transition
GO:0001889	liver development
GO:0003136	negative regulation of heart induction by canonical Wnt receptor signaling pathway
GO:0003337	mesenchymal to epithelial transition involved in metanephros morphogenesis
GO:0006351	transcription, DNA-templated
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0007016	cytoskeletal anchoring at plasma membrane
GO:0007155	cell adhesion
GO:0007160	cell-matrix adhesion
GO:0007398	ectoderm development
GO:0007403	glial cell fate determination
GO:0008285	negative regulation of cell proliferation
GO:0009950	dorsal/ventral axis specification
GO:0009954	proximal/distal pattern formation
GO:0010718	positive regulation of epithelial to mesenchymal transition
GO:0010909	positive regulation of heparan sulfate proteoglycan biosynthetic process
GO:0014010	Schwann cell proliferation
GO:0016055	Wnt signaling pathway
GO:0016337	single organismal cell-cell adhesion
GO:0022009	central nervous system vasculogenesis
GO:0030326	embryonic limb morphogenesis
GO:0030521	androgen receptor signaling pathway
GO:0030539	male genitalia development
GO:0030902	hindbrain development
GO:0030997	regulation of centriole-centriole cohesion
GO:0031016	pancreas development
GO:0031069	hair follicle morphogenesis
GO:0032331	negative regulation of chondrocyte differentiation
GO:0032355	response to estradiol
GO:0032481	positive regulation of type I interferon production
GO:0033077	T cell differentiation in thymus
GO:0033234	negative regulation of protein sumoylation
GO:0034333	adherens junction assembly
GO:0034394	protein localization to cell surface
GO:0035315	hair cell differentiation
GO:0036023	embryonic skeletal limb joint morphogenesis
GO:0042129	regulation of T cell proliferation
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042493	response to drug
GO:0042692	muscle cell differentiation
GO:0043065	positive regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043410	positive regulation of MAPK cascade
GO:0043587	tongue morphogenesis
GO:0044334	canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition
GO:0044336	canonical Wnt signaling pathway involved in negative regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045669	positive regulation of osteoblast differentiation
GO:0045671	negative regulation of osteoclast differentiation
GO:0045743	positive regulation of fibroblast growth factor receptor signaling pathway
GO:0045765	regulation of angiogenesis
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048145	regulation of fibroblast proliferation
GO:0048262	determination of dorsal/ventral asymmetry
GO:0048489	synaptic vesicle transport
GO:0048538	thymus development
GO:0048599	oocyte development
GO:0048617	embryonic foregut morphogenesis
GO:0048660	regulation of smooth muscle cell proliferation
GO:0050808	synapse organization
GO:0051145	smooth muscle cell differentiation
GO:0051149	positive regulation of muscle cell differentiation
GO:0060070	canonical Wnt signaling pathway
GO:0060440	trachea formation
GO:0060479	lung cell differentiation
GO:0060484	lung-associated mesenchyme development
GO:0060492	lung induction
GO:0060769	positive regulation of epithelial cell proliferation involved in prostate gland development
GO:0060789	hair follicle placode formation
GO:0060916	mesenchymal cell proliferation involved in lung development
GO:0061047	positive regulation of branching involved in lung morphogenesis
GO:0061154	endothelial tube morphogenesis
GO:0061324	canonical Wnt receptor signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation
GO:0070602	regulation of centromeric sister chromatid cohesion
GO:0071363	cellular response to growth factor stimulus
GO:0071681	cellular response to indole-3-methanol
GO:0072033	renal vesicle formation
GO:0072053	renal inner medulla development
GO:0072054	renal outer medulla development
GO:0072079	nephron tubule formation
GO:0072182	regulation of nephron tubule epithelial cell differentiation
GO:0090279	regulation of calcium ion import
GO:2000008	regulation of protein localization to cell surface

Cellular Component

GO:0000922	spindle pole
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0005912	adherens junction
GO:0005913	cell-cell adherens junction
GO:0005915	zonula adherens
GO:0005916	fascia adherens
GO:0005938	cell cortex
GO:0009898	cytoplasmic side of plasma membrane
GO:0016020	membrane
GO:0016328	lateral plasma membrane
GO:0016342	catenin complex
GO:0030018	Z disc
GO:0030027	lamellipodium
GO:0030054	cell junction
GO:0030057	desmosome
GO:0030877	beta-catenin destruction complex
GO:0031528	microvillus membrane
GO:0032993	protein-DNA complex
GO:0043198	dendritic shaft
GO:0045202	synapse
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome
GO:0070369	beta-catenin-TCF7L2 complex
GO:0071944	cell periphery