CTNND1 (catenin (cadherin-associated protein), delta 1)

2010-05-01   Michael R Dohn , Albert B Reynolds 

Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA




Atlas Image
CTNND1/p120 gene structure. DNA of CTNND1 gene (NM_001085458.1) composed of 19 coding exons (red). Untranslated regions are depicted in green.


DNA contains 57419 bp composed of 21 exons, 19 of which are coding exons.


Alternative transcription produces several distinct mRNAs ranging from 5676 bp to 6329 bp, transcribed in centromeric to telomeric orientation, with open reading frames ranging from 2802 bp to 2904 bp.




Atlas Image
CTNND1/p120 protein structure. p120 contains four translational start sites (1-4, arrows) and three alternatively transcribed exons A, B, and C (red boxes). Isoform-1 contains an amino-terminal coiled coil domain (CC), and a phosphorylation domain (PD) is present in all but isoform-4. All isoforms contain a central Armadillo repeat domain (gray boxes).


This gene encodes a member of the Armadillo (Arm) family of proteins, which function in cell-cell adhesion and signal transduction, and is the prototype for a subfamily of proteins that includes p120-catenin (hereafter p120), delta-catenin, p0071, and plakophilins 1-3 (PKP1, PKP2, PKP3). CTNND1/p120 has four distinct translation start codons (isoforms 1-4) and three alternatively spliced exons (A, B, and C), potentially resulting in 32 isoforms as products of alternative splicing. A coiled-coil domain is present in the extreme amino-terminus of the long-isoform (isoform-1), and an amino terminal phosphorylation domain is present in all but the shortest isoform (isoform-4). All p120 isoforms contain a central Arm domain consisting of nine Arm repeats. p120 has been shown to be post-translationally modified by phosphorylation on tyrosine, serine, and threonine residues, as well as by cleavage by the protease calpain. Phosphorylation of p120 may be regulated in part via interactions with non-receptor tyrosine kinases, (including Fer, Fyn, and Yes) and protein tyrosine phosphatases (including PTPmu, SHP-1, and DEP-1).


p120 isoforms have been detected in all tissues examined, although cells of epithelial origin tend to predominantly express isoform 3, whereas motile, fibroblastoid cells often express isoform 1.


Cell-cell junctions (bound to cadherin molecules), cytoplasm, and nucleus.


CTNND1/p120 was originally identified as a substrate for the Src oncogene and for various receptor tyrosine kinases, though its most prominent role is in stabilizing adherens junctions. Via its Arm domain, p120 binds to the juxtamembrane region of the cytoplasmic tails of type I and II cadherins. Upon removal of p120, by either gene knock-out or shRNA-mediated knock-down, adherens junction components, namely cadherin, beta-catenin, and alpha-catenin, are internalized and rapidly degraded. p120 also likely participates in the rearrangement of the actin cytoskeleton via regulation of Rho family GTPases, and p120 may also influence gene expression via its interaction in the nucleus and cytoplasm with the transcriptional repressor Kaiso.


Pan troglodytes - CTNND1; Canis lupus familiaris - CTNND1; Bos taurus - CTNND1; Mus musculus - Ctnnd1; Rattus norvegicus - Ctnnd1; Gallus gallus - RCJMB04_21j12; Danio rerio - LOC556726.



While p120 is frequently decreased in a wide variety of cancers, the only mutated p120 identified to date is found in colonic SW48 cells. In these cells, a heterozygous nonsense mutation in exon 7 at nucleotide 1908 (C to T) yields a premature stop codon that truncates the protein in the third ARM repeat. Several other cDNA abnormalities, including deletion of exon 17, retention of intron 19, or retention of both introns 19 and 20, were also identified in both p120 alleles in these cells, resulting in premature stop codons that eliminate the normal p120 COOH terminus.

Implicated in

Entity name
Various cancers
p120s ability to stabilize E-cadherin, a tumor suppressor, suggests that p120 may play a role in tumor and/or metastasis suppression. Indeed, p120 is often lost, downregulated, or mislocalized in human colon, breast, prostate, lung, and other carcinomas. Total p120 knockout is embryonically lethal in mice, but conditional knockout studies have shown that p120 loss in the salivary gland induces dysplasia indistinguishable from high-grade intraepithelial neoplasia, and p120 ablation in the epidermis induces hyperproliferation and inflammation. However, recent studies have also identified a requirement for p120 in anchorage-independent growth of both tumor cell lines and oncogene-transformed cell lines. Moreover, a role for p120 and its binding partner Kaiso in Wnt signaling, which is often hyperactive in colon cancer, is becoming increasingly evident.
Entity name
Breast cancer
cDNA microarray analysis revealed a downregulation of p120 in invasive breast cancers compared to their respective benign control breast tissues, and immunohistochemical analyses of tissue samples from 341 invasive breast cancer patients found that p120 downregulation predicted a 3.1-fold risk in breast cancer death.
Additionally, translation initiation factor eIF4GI-enhanced translation of IRES-containing p120 mRNAs has been shown to promote tumor emboli formation in inflammatory breast cancer.
Entity name
Lung cancer
A study of 138 patients with non-small cell lung cancer found that p120 membrane localization was reduced and ectopic cytoplasmic expression was increased in lung cancer tissues. Abnormal p120 localization correlated with TNM stage and lymph node metastasis.
Entity name
Skin cancer
p120 was found to be altered in squamous cell carcinomas in humans, and conditional ablation of p120 in the epidermis in mice led to progressive development of skin neoplasias.


Pubmed IDLast YearTitleAuthors
103218381999Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen.Aho S et al
109807052000Inhibition of RhoA by p120 catenin.Anastasiadis PZ et al
189506212009PDGF receptor activation induces p120-catenin phosphorylation at serine 879 via a PKCalpha-dependent pathway.Brown MV et al
156639512005Structure of the armadillo repeat domain of plakophilin 1.Choi HJ et al
102070851999The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor.Daniel JM et al
146100552003A core function for p120-catenin in cadherin turnover.Davis MA et al
163990752006Blocked acinar development, E-cadherin reduction, and intraepithelial neoplasia upon ablation of p120-catenin in the mouse salivary gland.Davis MA et al
191884962009An essential role for p120-catenin in Src- and Rac1-mediated anchorage-independent cell growth.Dohn MR et al
18515491991PDGF, CSF-1, and EGF induce tyrosine phosphorylation of p120, a pp60src transformation-associated substrate.Downing JR et al
111713752001p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion.Grosheva I et al
123708292002The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn).Holsinger LJ et al
124278692002A novel role for p120 catenin in E-cadherin function.Ireton RC et al
17036311991Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells.Kanner SB et al
108354202000The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin.Keilhack H et al
96536411998Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.Keirsebilck A et al
155431382004Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin.Kim SW et al
191623672009Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer.Liu Y et al
149969112004EGFR signaling to p120-catenin through phosphorylation at Y228.Mariner DJ et al
109318682000p120 catenin regulates the actin cytoskeleton via Rho family GTPases.Noren NK et al
171961662007Ischemia promotes calpain-mediated degradation of p120-catenin in SH-SY5Y cells.Ohno H et al
170843602006Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals.Park JI et al
159357742005Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.Park JI et al
164697072006p120-catenin mediates inflammatory responses in the skin.Perez-Moreno M et al
126401142003p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction.Piedra J et al
114455352001The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor.Prokhortchouk A et al
24690031989Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene.Reynolds AB et al
195259342009Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer.Silvera D et al
190153202008p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression.Soto E et al
158171512005The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.Spring CM et al
201511512010Altered expression of p120catenin predicts poor outcome in invasive breast cancer.Talvinen K et al
124924992002Altered expression of the catenin p120 in human cancer: implications for tumor progression.Thoreson MA et al
169352802006p120 serine and threonine phosphorylation is controlled by multiple ligand-receptor pathways but not cadherin ligation.Xia X et al
128852542003Adhesion-associated and PKC-modulated changes in serine/threonine phosphorylation of p120-catenin.Xia X et al
146100562003Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.Xiao K et al
107539362000Receptor protein-tyrosine phosphatase RPTPmu binds to and dephosphorylates the catenin p120(ctn).Zondag GC et al
170304442007Diverse functions of p120ctn in tumors.van Hengel J et al

Other Information

Locus ID:

NCBI: 1500
MIM: 601045
HGNC: 2515
Ensembl: ENSG00000198561


dbSNP: 1500
ClinVar: 1500
TCGA: ENSG00000198561


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Adherens junctionKEGGko04520
Leukocyte transendothelial migrationKEGGko04670
Adherens junctionKEGGhsa04520
Leukocyte transendothelial migrationKEGGhsa04670
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Infectious diseaseREACTOMER-HSA-5663205
Signal TransductionREACTOMER-HSA-162582
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated vascular permeabilityREACTOMER-HSA-5218920
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Adherens junctions interactionsREACTOMER-HSA-418990
Listeria monocytogenes entry into host cellsREACTOMER-HSA-8876384
InlA-mediated entry of Listeria monocytogenes into host cellsREACTOMER-HSA-8876493

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
146100552003A core function for p120-catenin in cadherin turnover.278
124278692002A novel role for p120 catenin in E-cadherin function.209
146100562003Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.171
203713492010Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.127
161206452005p120-Catenin regulates clathrin-dependent endocytosis of VE-cadherin.117
214817892011Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene.90
230711562012p120-catenin binding masks an endocytic signal conserved in classical cadherins.82
184079992008A p120 catenin isoform switch affects Rho activity, induces tumor cell invasion, and predicts metastatic disease.77
124924992002Altered expression of the catenin p120 in human cancer: implications for tumor progression.64
158578342005Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn.62


Michael R Dohn ; Albert B Reynolds

CTNND1 (catenin (cadherin-associated protein), delta 1)

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

Online version: http://atlasgeneticsoncology.org/gene/40197/ctnnd1-(catenin-(cadherin-associated-protein)-delta-1)