From Wikipedia, the free encyclopedia
|
Catenin (cadherin-associated protein), beta 1, 88kDa |

PDB rendering based on
1dow. |
|
Available structures |
| 1dow, 1g3j, 1i7w, 1i7x, 1jdh, 1jpp, 1jpw, 1luj, 1m1e, 1qz7, 1t08, 1th1, 1v18, 2bct, 2gl7, 3bct |
|
Identifiers |
| Symbols |
CTNNB1; CTNNB;
FLJ25606 |
| External IDs |
OMIM: 116806 MGI: 88276 HomoloGene: 1434 GeneCards: CTNNB1 Gene |
|
|
|
RNA expression pattern |
 |
| More reference expression
data |
|
Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
1499 |
12387 |
|
| Ensembl |
ENSG00000168036 |
ENSMUSG00000006932 |
|
| UniProt |
P35222 |
Q3UZT7 |
|
| RefSeq (mRNA) |
XM_001133660 |
NM_007614 |
|
| RefSeq (protein) |
XP_001133660 |
NP_031640 |
|
| Location (UCSC) |
Chr 3:
41.22 - 41.26 Mb |
Chr 9:
120.78 - 120.81 Mb |
|
| PubMed search |
[1] |
[2] |
|
|
Figure 2. β-catenin ( β) can interact with several
different proteins inside cells. The interaction of β-catenin with
other proteins is often regulated by the reversible attachment of
phosphate ( P).
|
Overview of signal transduction pathways involved in apoptosis.
|
Beta-catenin (or β-catenin) is a protein that in humans is
encoded by the CTNNB1 gene.[1]
In Drosophila, the homologous protein is
called armadillo. β-catenin is a subunit of the cadherin protein complex and
has been implicated as an integral component in the Wnt
signaling pathway.
Structure
When β-catenin was sequenced it was found to be a member of the
armadillo family of proteins. These proteins have multiple copies
of the so-called armadillo
repeat domain which is specialized for protein-protein binding.
When β-catenin is not associated with cadherins and alpha-catenin, it can interact with other
proteins such as ICAT and
APC.
Function
β-catenin is part of a complex of proteins that constitute adherens
junctions (AJs). AJs are necessary for the creation and
maintenance of epithelial cell layers by regulating cell
growth and adhesion between cells. β-catenin also
anchors the actin cytoskeleton and may
be responsible for transmitting the contact inhibition signal that
causes cells to stop dividing once the epithelial sheet is
complete.[2]
Recent evidence suggests that β-catenin plays an important role
in various aspects of liver biology including liver development
(both embryonic and postnatal), liver regeneration following
partial hepatectomy, HGF-induced hepatomegaly, liver zonation, and
pathogenesis of liver cancer.[3]
Role in the Wnt signaling
pathway
When Wnt is not present, GSK-3 (a kinase) constitutively phosphorylates
the β-catenin protein. β-catenin is associated with axin (scaffolding protein)
complexed with GSK3 and APC (adenomatosis polyposis coli). The
creation of said complex acts to substantially increase the
phosphorylation of β-catenin by facilitating the action of GSK3.
When β-catenin is phosphorylated it is degraded and thus will not
build up in the cell to a significant level. When Wnt binds to frizzled (Fz), its receptor,
dishevelled (Dsh) is
recruited to the membrane. GSK3 is inhibited by the activation of
Dsh by Fz. Because of this, β-catenin is permitted to build up in
the cytosol and can be
subsequently translocated into the nucleus to perform a variety of functions.
It can act in conjunction with TCF
to activate specific genes as well as cause the export of TCF from
the nucleus.
Clinical
significance
β-catenin can function as an oncogene.[4]
An increase in β-catenin production has been noted in those people
who have basal cell carcinoma and leads to
the increase in proliferation of related tumors.[5]
Mutations in this gene are a cause of colorectal cancer (CRC),
pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer.
Finally, this protein binds to the product of the APC gene,
which is mutated in adenomatous polyposis of the colon.
Interactions with other
proteins
As mentioned above, β-catenin contains armadillo repeats and is
able to bind to other proteins. Inside cells, β-catenin can be
found in complexes with cadherins, transcription factors
(TF in Figure 2) and other proteins such as axin,
a component of the Wnt signalling
pathway and galectin-3, beta-galactoside-binding protein. The
ability of β-catenin to bind to other proteins is regulated by tyrosine
kinases[6]
and serine kinases such as GSK-3.[7]
When β-catenin is not assembled in complexes with cadherins, it
can form a complex with axin. While bound to axin, β-catenin can be
phosphorylated by GSK-3, which creates
a signal for the rapid ubiquitin-dependent degradation of β-catenin
by proteosomes.
Various signals such as the Wnt signalling pathway can inhibit
GSK-3-mediated phosphorylation of β-catenin,[8]
allowing β-catenin to go to the cell nucleus, interact with
transcription factors, and regulate gene transcription.
β-catenin can be phosphorylated by other kinases such as protein
kinase A (PKA). Phosphorylation of β-catenin by PKA has been
associated with reduced degradation of β-catenin, increased levels
of β-catenin in the nucleus and interaction of β-catenin with TCF
family transcription factors to regulate gene expression.[9]
In addition, β-catenin has been shown to interact with:
- Androgen
receptor,[10][11][12][13][14][15]
APC,[16][17][18][19][20][21][22][23]
AXIN1,[24][25]
- CBY1,[26]
- CDH1,[27][17][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]
CDH2,[49][50]
CDH3,[51][47]
- CDK5R1,[52]
- CHUK,[53]
CTNNA1,[28][54][37][55][56]
CTNND1,[32][17]
- EGFR,[32][57][41]
- FHL2,[58]
- GSK3B,[19][59]
- HER2/neu,[57][33][60]
- HNF4A,[14]
- IKK2,[53]
- LEF1,[61][62][63][64]
- MAGI1,[42]
MUC1,[65][66][34][67][68][69][70]
- NR5A1,[71][72]
- PCAF,[73]
PHF17,[74]
Plakoglobin,[32][17]
PTPN14,[75]
PTPRF,[33][76]
PTPRK,[77]
PSEN1,[78][79][80]
- RuvB-like 1,[81]
- SMAD7,[61]
- SLC9A3R1,[36]
SMARCA4,[82]
- USP9X,[83]
and
- VE-cadherin.[84][85]
See also
References
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Further
reading
- Kikuchi A (2000). "Regulation of
β-catenin signaling in the Wnt pathway.". Biochem. Biophys.
Res. Commun. 268 (2): 243–8. doi:10.1006/bbrc.1999.1860. PMID 10679188.
- Wilson PD (2001). "Polycystin:
new aspects of structure, function, and regulation.". J. Am.
Soc. Nephrol. 12 (4): 834–45. PMID 11274246.
- Kalluri R, Neilson EG (2004).
"Epithelial-mesenchymal transition and its implications for
fibrosis.". J. Clin. Invest. 112 (12):
1776–84. doi:10.1172/JCI200320530. PMID 14679171.
- De Ferrari GV, Moon RT (2007).
"The ups and downs of Wnt signaling in prevalent neurological
disorders.". Oncogene 25 (57): 7545–53.
doi:10.1038/sj.onc.1210064. PMID 17143299.
External
links
This article incorporates text from the United States
National Library of Medicine, which is in the public
domain.
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PDB Gallery |
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1dow: CRYSTAL STRUCTURE OF A CHIMERA OF
BETA-CATENIN AND ALPHA-CATENIN
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1g3j: CRYSTAL STRUCTURE OF THE
XTCF3-CBD/BETA-CATENIN ARMADILLO REPEAT COMPLEX
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1i7w: BETA-CATENIN/PHOSPHORYLATED E-CADHERIN
COMPLEX
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1i7x: BETA-CATENIN/E-CADHERIN COMPLEX
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1jdh: CRYSTAL STRUCTURE OF BETA-CATENIN AND HTCF-4
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1jpp: The Structure of a beta-Catenin Binding
Repeat from Adenomatous Polyposis Coli (APC) in Complex with
beta-Catenin
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1jpw: Crystal Structure of a Human Tcf-4 /
beta-Catenin Complex
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1luj: Crystal Structure of the Beta-catenin/ICAT
Complex
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1m1e: Beta-catenin armadillo repeat domain bound
to ICAT
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1qz7: Beta-catenin binding domain of Axin in
complex with beta-catenin
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1t08: Crystal structure of beta-catenin/ICAT
helical domain/unphosphorylated APC R3
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1th1: Beta-catenin in complex with a
phosphorylated APC 20aa repeat fragment
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1v18: THE CRYSTAL STRUCTURE OF BETA-CATENIN
ARMADILLO REPEAT COMPLEXED WITH A PHOSPHORYLATED APC 20MER REPEAT.
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2bct: THE ARMADILLO REPEAT REGION FROM MURINE
BETA-CATENIN
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2gl7: Crystal Structure of a
beta-catenin/BCL9/Tcf4 complex
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3bct: THE ARMADILLO REPEAT REGION FROM MURINE
BETA-CATENIN
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Proteins of the cytoskeleton |
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Human |
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Actins (A1, A2, B, C1, G1, G2)
Myosins (1A, 1B, 1C, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11,
MYH13, MYH14, MYH15,
MYH16)
Tropomodulin
(1, 2, 3, 4) · Troponin (T 1 2 3, C
1 2, I 1 2 3) ·
Tropomyosin (1, 2, 3, 4)
other related: Actinin ( 1, 2, 3, 4) · Arp2/3 complex · actin depolymerizing
factors ( Cofilin
( 1, 2) · Destrin) · Gelsolin · Profilin ( 1, 2)
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Other
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type 1 and 2 ( Cytokeratin, type I, type II) · type 3 ( Desmin, GFAP, Peripherin, Vimentin) · type 4 ( Internexin, Nestin, Neurofilament, Synemin, Syncoilin) · type 5 ( Lamin A, B)
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Other
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Nonhuman |
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