Catenin alpha-1

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CTNNA1
Protein CTNNA1 PDB 1dov.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CTNNA1, CAP102, Catenin, MDPT2, catenin alpha 1
External IDs MGI: 88274 HomoloGene: 1433 GeneCards: CTNNA1
RNA expression pattern
PBB GE CTNNA1 210844 x at fs.png

PBB GE CTNNA1 200764 s at fs.png

PBB GE CTNNA1 200765 x at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_009818

RefSeq (protein)

NP_033948.1
NP_033948

Location (UCSC) Chr 5: 138.61 – 138.94 Mb Chr 18: 35.12 – 35.25 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene.[3][4] αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of actin filaments to the sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function.

Structure[edit]

Human αE-catenin protein is 100.0 kDa and 906 amino acids.[5] Catenins (α,β,and γ (also known as plakoglobin)) were originally identified in complex with E-cadherin, an epithelial cell adhesion protein. αE-catenin is highly expressed in cardiac muscle[6][7] and is homologous to the protein vinculin; however, aside from vinculin, αE-catenin has no homology to established actin-binding proteins. The N-terminus of αE-catenin binds β-catenin or γ-catenin/plakoglobin, and the C-terminus binds actin directly or indirectly via vinculin or α-actinin.[8]

Function[edit]

Though αE-catenin exhibits substantial expression in cardiac muscle, αE-catenin is most well known for role in metastasizing tumor cells.[9] αE-catenin also plays a role in epithelial tissue, both at adherens junctions and in signaling pathways.[10]

In cardiomyocytes, αE-catenin is present in cell to cell regions known as adherens junctions which lie within intercalated discs; these junctions anchor the actin cytoskeleton to the sarcolemma and provide strong cell adhesion.[11]

Functional αE-catenin is required for normal embryonic development, as a mutation eliminating the C-terminal 1/3 of the protein resulting in a complete loss-of-function phenotype showed disruption of the trophoblast epithelium and arrested development at the blastocyst stage.[12]

αE-catenin specifically, not β- or γ-catenin, binds F-actin and organizes and tethers the filaments at regions of cell-cell contact. Studies show that full-length αE-catenin binds and bundles F-actin in a superior fashion relative to individual N-terminal or C-terminal domains.[13]

αE-catenin, along with β-catenin and plakoglobin form distinct complexes with N-cadherin that are involved in forming cell-cell contacts and differentiation of cardiomyocytes. Catenin-N-cadherin complexes are apparently necessary for and precede the first cell to cell contact, precursory to gap junction formation.[14] The anchorage of cadherin-catenin complexes to actin filaments by αE-catenin is regulated by tyrosine phosphorylation.[15]

Functional insights into αE-catenin function have come from studies employing transgenesis. Mice harboring a cardiac-specific deletion of αE-catenin exhibited abnormalities in cardiac dimensions and function, representative of dilated cardiomyopathy. This was further characterized by disorganization of intercalated disc structures and mitochondria, as well as compensatory increases in β-catenin and decreases in localization of cadherin and vinculin at intercalated discs. Knockout mice also exhibited high susceptibility to death following stress.[16]

Clinical Significance[edit]

Interactions[edit]

αE-catenin has been shown to interact with:

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
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  4. ^ "Entrez Gene: CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa". 
  5. ^ "Protein sequence of human CTNNA1 (Uniprot ID: P35221)". Cardiac Organellar Protein Atlas Knolwedgebase (COPaKB). Retrieved 3 July 2015. 
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  18. ^ Daniel JM, Reynolds AB (September 1995). "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin". Mol. Cell. Biol. 15 (9): 4819–24. doi:10.1128/mcb.15.9.4819. PMC 230726Freely accessible. PMID 7651399. 
  19. ^ Oyama T, Kanai Y, Ochiai A, Akimoto S, Oda T, Yanagihara K, Nagafuchi A, Tsukita S, Shibamoto S, Ito F (December 1994). "A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines". Cancer Res. 54 (23): 6282–7. PMID 7954478. 
  20. ^ a b Roe S, Koslov ER, Rimm DL (June 1998). "A mutation in alpha-catenin disrupts adhesion in clone A cells without perturbing its actin and beta-catenin binding activity". Cell Adhes. Commun. 5 (4): 283–96. doi:10.3109/15419069809040298. PMID 9762469. 
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Further reading[edit]