Catenin alpha-1

CTNNA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H6G, 4EHP, 4IGG
Identifiers
Aliases	CTNNA1, CAP102, Catenin, MDPT2, catenin alpha 1
External IDs	OMIM: 116805; MGI: 88274; HomoloGene: 1433; GeneCards: CTNNA1; OMA:CTNNA1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q31.2 Start 138,610,967 bp[1] End 138,935,034 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 B1|18 18.89 cM Start 35,251,912 bp[2] End 35,387,832 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in epithelium of colon Achilles tendon amniotic fluid nasal epithelium corpus callosum tibial nerve middle frontal gyrus mucosa of pharynx bronchial epithelial cell ventricular zone Top expressed in medullary collecting duct endothelial cell of lymphatic vessel ciliary body conjunctival fornix retinal pigment epithelium Paneth cell Epithelium of choroid plexus iris left lung lobe vestibular membrane of cochlear duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function gamma-catenin binding actin filament binding beta-catenin binding protein binding vinculin binding structural molecule activity protein heterodimerization activity RNA binding cadherin binding identical protein binding Cellular component acrosomal vesicle cytoskeleton intracellular membrane-bounded organelle intercalated disc actin cytoskeleton adherens junction catenin complex cytosol membrane plasma membrane cytoplasm cell-cell junction cell junction lamellipodium Golgi apparatus focal adhesion zonula adherens flotillin complex Biological process positive regulation of smoothened signaling pathway actin filament organization response to estrogen regulation of cell population proliferation response to organic cyclic compound negative regulation of extrinsic apoptotic signaling pathway in absence of ligand negative regulation of neuroblast proliferation establishment or maintenance of cell polarity positive regulation of extrinsic apoptotic signaling pathway in absence of ligand gap junction assembly negative regulation of cell motility negative regulation of integrin-mediated signaling pathway apical junction assembly cell adhesion human ageing male gonad development protein heterooligomerization adherens junction organization positive regulation of muscle cell differentiation ovarian follicle development odontogenesis of dentin-containing tooth cellular response to indole-3-methanol negative regulation of apoptotic process axon regeneration epithelial cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1495 12385 Ensembl ENSG00000044115 ENSMUSG00000037815 UniProt P35221 P26231 RefSeq (mRNA) NM_001290307 NM_001290309 NM_001290310 NM_001290312 NM_001903 NM_001323982 NM_001323983 NM_001323984 NM_001323985 NM_001323986 NM_001323987 NM_001323988 NM_001323989 NM_001323990 NM_001323991 NM_001323992 NM_001323993 NM_001323994 NM_001323995 NM_001323996 NM_001323997 NM_001323998 NM_001323999 NM_001324000 NM_001324001 NM_001324002 NM_001324003 NM_001324004 NM_001324005 NM_001324006 NM_001324007 NM_001324008 NM_001324009 NM_001324010 NM_001324011 NM_001324012 NM_001324013 NM_009818 RefSeq (protein) NP_001277236 NP_001277238 NP_001277239 NP_001277241 NP_001310911 NP_001310912 NP_001310913 NP_001310914 NP_001310915 NP_001310916 NP_001310917 NP_001310918 NP_001310919 NP_001310920 NP_001310921 NP_001310922 NP_001310923 NP_001310924 NP_001310925 NP_001310926 NP_001310927 NP_001310928 NP_001310929 NP_001310930 NP_001310931 NP_001310932 NP_001310933 NP_001310934 NP_001310935 NP_001310936 NP_001310937 NP_001310938 NP_001310939 NP_001310940 NP_001310941 NP_001310942 NP_001894 NP_001277236.1 NP_033948 Location (UCSC) Chr 5: 138.61 – 138.94 Mb Chr 18: 35.25 – 35.39 Mb PubMed search [3] [4]
Wikidata
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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

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

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

Interactions

αE-catenin has been shown to interact with:

See also

• Alpha-catenin

References

Further reading