8.A.160.  The Catenin (Catenin) Family 

Catenin δ-1 is a key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of C-, E- and N-cadherins, being critical for their surface stability (Davis et al. 2003, Ishiyama et al. 2010). Beside cell-cell adhesion, it regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (Daniel and Reynolds 1999, Ishiyama et al. 2010). It is implicated in both cell transformation by SRC and ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (Hosking et al. 2007). Mutations in the beta-catenin gene (CTNNB1), lead to aberrant immunohistochemical expression of beta-catenin, and this represents a key mechanism of WNT/beta-catenin pathway alteration in ovarian cancer (Angelico et al. 2021). Beta-catenin and AQP1 are co-expressed in a sub-group of ovarian tumors and play important roles in carcinogenesis (Angelico et al. 2021).

p120 catenin recruits human papillomavirus (HPV) to the transmembrane protease, gamma-secretase, to promote virus infection (Harwood et al. 2020). During internalization and trafficking, HPV moves from the cell surface to the endosome where γ-secretase promotes insertion of the viral L2 capsid protein into the endosomal membrane. Protrusion of L2 through the endosomal membrane into the cytosol allows the recruitment of cytosolic host factors that target the virus to the Golgi, en route for productive infection. Cytosolic p120 catenin, likely via an unidentified transmembrane protein, interacts with HPV at early time-points during viral internalization and trafficking. In the endosome, p120 is not required for low pH-dependent disassembly of the HPV L1 capsid protein from the incoming virion. Rather, p120 is required for HPV to interact with gamma-secretase - an interaction that ensures the virus is transported along a productive route (Harwood et al. 2020).




Abe, K. and M. Takeichi. (2008). EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt. Proc. Natl. Acad. Sci. USA 105: 13-19.

Akiyama, H., J.P. Lyons, Y. Mori-Akiyama, X. Yang, R. Zhang, Z. Zhang, J.M. Deng, M.M. Taketo, T. Nakamura, R.R. Behringer, P.D. McCrea, and B. de Crombrugghe. (2004). Interactions between Sox9 and β-catenin control chondrocyte differentiation. Genes Dev. 18: 1072-1087.

Angelico, G., A. Ieni, R. Caltabiano, A. Santoro, F. Inzani, S. Spadola, G. Tuccari, A. Macrì, and G.F. Zannoni. (2021). Evaluation of Beta-Catenin Subcellular Localization and Water Channel Protein AQP1 Expression as Predictive Markers of Chemo-Resistance in Ovarian High-Grade Serous Carcinoma: Comparative Study between Preoperative Peritoneal Biopsies and Surgical Samples. Diagnostics (Basel) 11:.

Daniel, J.M. and A.B. Reynolds. (1999). The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol. Cell Biol. 19: 3614-3623.

Davis, M.A., R.C. Ireton, and A.B. Reynolds. (2003). A core function for p120-catenin in cadherin turnover. J. Cell Biol. 163: 525-534.

Furukawa, M., Y.J. He, C. Borchers, and Y. Xiong. (2003). Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat. Cell Biol. 5: 1001-1007.

Harwood, M.C., A.J. Dupzyk, T. Inoue, D. DiMaio, and B. Tsai. (2020). p120 catenin recruits HPV to γ-secretase to promote virus infection. PLoS Pathog 16: e1008946.

Hoorn, E.J. and J.H.F. de Baaij. (2022). Chloride-sensitive signaling turns the potassium switch on. Kidney Int 102: 956-958.

Hosking, C.R., F. Ulloa, C. Hogan, E.C. Ferber, A. Figueroa, K. Gevaert, W. Birchmeier, J. Briscoe, and Y. Fujita. (2007). The transcriptional repressor Glis2 is a novel binding partner for p120 catenin. Mol. Biol. Cell 18: 1918-1927.

Ishiyama, N., S.H. Lee, S. Liu, G.Y. Li, M.J. Smith, L.F. Reichardt, and M. Ikura. (2010). Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion. Cell 141: 117-128.

Jiang, S., H.K. Avraham, S.Y. Park, T.A. Kim, X. Bu, S. Seng, and S. Avraham. (2005). Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven. J Neurochem 92: 1191-1203.

Kim, S., H.I. Choi, H.J. Ryu, J.H. Park, M.D. Kim, and S.Y. Kim. (2004). ARIA, an Arabidopsis arm repeat protein interacting with a transcriptional regulator of abscisic acid-responsive gene expression, is a novel abscisic acid signaling component. Plant Physiol. 136: 3639-3648.

Matthews, P.M., A. Pinggera, D. Kampjut, and I.H. Greger. (2021). Biology of AMPA receptor interacting proteins - From biogenesis to synaptic plasticity. Neuropharmacology 197: 108709.

Ohta, A., F.R. Schumacher, Y. Mehellou, C. Johnson, A. Knebel, T.J. Macartney, N.T. Wood, D.R. Alessi, and T. Kurz. (2013). The CUL3-KLHL3 E3 ligase complex mutated in Gordon''s hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem. J. 451: 111-122.

Wu, G. and J.B. Peng. (2013). Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. FEBS Lett. 587: 1717-1722.

Yamada, S., S. Pokutta, F. Drees, W.I. Weis, and W.J. Nelson. (2005). Deconstructing the cadherin-catenin-actin complex. Cell 123: 889-901.


TC#NameOrganismal TypeExample

p120 catenin (catenin δ-1) (CTND1; CTNND1) of 968 aas and 0 TMSs. During internalization and trafficking, human papillomavirus (HPV) moves from the cell surface to the endosome where the transmembrane protease, gamma-secretase, promotes insertion of the viral L2 capsid protein into the endosome membrane (Harwood et al. 2020).

p120 catenin (catenin δ1) of Homo sapiens


Uncharacterized protein of 1086 aas.

UP of Trypanosoma cruzi


ARM REPEAT PROTEIN INTERACTING WITH ABF2, ARIA, of 710 aas. At may act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It acts as a positive regulator of the ABA response via the modulation of the transcriptional activity of ABF2, a transcription factor which controls ABA-dependent gene expression via the G-box-type ABA-responsive elements. It is a negative regulator of seed germination and young seedling growth (Kim et al. 2004).

ARIA of Arabidopsis thaliana (Mouse-ear cress)


Kelch-like protein receptor of 500 aas and possibly 6 or more C-terminal TMSs. It is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation (Jiang et al. 2005). It may be a subunit of AMPA receptors (Matthews et al. 2021).

KLHL2 of Homo sapiens


Kelch-like protein 3, KLHL3, of 587 aas and 0-2 N-terminal TMSs. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (Furukawa et al. 2003, Wu and Peng 2013). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (Ohta et al. 2013, Wu and Peng 2013). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney. It is involved in chloride-sensitive signaling that turns the potassium switch on (Hoorn and de Baaij 2022).

KLHL3 of Homo sapiens


TC#NameOrganismal TypeExample

Catenin beta-1, Ctnnb1, of 781 aas and 0 TMSs. It is a key downstream component of the canonical Wnt signaling pathway (Akiyama et al. 2004). 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.It is also involved in the regulation of cell adhesion as a component of an E-cadherin:catenin adhesion complex (Yamada et al. 2005; Abe and Takeichi 2008).

Ctnnb1 of Mus musculus