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Catenin alpha-1

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CTNNA1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCTNNA1, CAP102, Catenin, MDPT2, catenin alpha 1
External IDsOMIM: 116805; MGI: 88274; HomoloGene: 1433; GeneCards: CTNNA1; OMA:CTNNA1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1495

12385

Ensembl

ENSG00000044115

ENSMUSG00000037815

UniProt

P35221

P26231

RefSeq (mRNA)

NM_009818

RefSeq (protein)

NP_033948

Location (UCSC)Chr 5: 138.61 – 138.94 MbChr 18: 35.25 – 35.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene.[5][6] 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

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Human αE-catenin protein is 100.0 kDa and 906 amino acids.[7] 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[8][9] 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.[10]

Function

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Though αE-catenin exhibits substantial expression in cardiac muscle, αE-catenin is most well known for role in metastasizing tumor cells.[11] αE-catenin also plays a role in epithelial tissue, both at adherens junctions and in signaling pathways.[12]

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.[13]

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.[14]

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.[15]

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.[16] The anchorage of cadherin-catenin complexes to actin filaments by αE-catenin is regulated by tyrosine phosphorylation.[17]

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.[18]

Clinical significance

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Interactions

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αE-catenin has been shown to interact with:

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000044115 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037815 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. ^ "Entrez Gene: CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa".
  7. ^ "Protein sequence of human CTNNA1 (Uniprot ID: P35221)". Cardiac Organellar Protein Atlas Knolwedgebase (COPaKB). Archived from the original on 4 July 2015. Retrieved 3 July 2015.
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  9. ^ Ehler E, Horowits R, Zuppinger C, Price RL, Perriard E, Leu M, Caroni P, Sussman M, Eppenberger HM, Perriard JC (May 2001). "Alterations at the intercalated disk associated with the absence of muscle LIM protein". The Journal of Cell Biology. 153 (4): 763–72. doi:10.1083/jcb.153.4.763. PMC 2192386. PMID 11352937.
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  19. ^ Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 (5140): 1734–7. Bibcode:1993Sci...262.1734S. doi:10.1126/science.8259519. PMID 8259519.
  20. ^ 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 230726. PMID 7651399.
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Further reading

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