Property Summary

NCBI Gene PubMed Count 80
PubMed Score 237.42
PubTator Score 114.84

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Expression

  Differential Expression (4)

Disease log2 FC p
interstitial lung disease 1.800 4.0e-02
active Crohn's disease 3.201 2.6e-03
active ulcerative colitis 4.392 1.0e-03
pancreatic cancer 1.300 2.4e-03

Gene RIF (61)

PMID Text
26820620 Genetic variants in CLDN2 and MORC4 genes were associated with chronic pancreatitis in Indian patients.
26568313 The authors conclude that claudin-2 forms gated paracellular channels.
26212084 The current study reveals an important and novel mechanism for VDR by regulation of epithelial barriers.
26110235 Association of claudin2 (rs7057398) polymorphism with idiopathic recurrent acute pancreatitis and progression of the disease to chronic pancreatitis.
26061016 Quercetin decreases claudin-2 expression mediated by up-regulation of miR-16 expression and instability of claudin-2 mRNA in lung adenocarcinoma cells.
26023235 Phosphorylation state of the tyrosine of claudin-1 and claudin-2 regulates interaction with ZO1.
25948735 TNF--alpha modifies claudin-2 expression in tubular cells and this can have both short-term and long-term effects on transport and barrier functions.
25823815 Pan-inhibition of SFK signaling pathways elevated Claudin-2 expression levels in breast cancer cells. Loss of Yes or Fyn induces Claudin-2 expression; whereas, diminished Lyn levels impairs Claudin-2 expression in breast cancer cells.
25694446 PKCiota binds to Rab14 and that PKCiota requires Rab14 for its correct distribution in cells. As with Rab14, PKCiota protects claudin-2 from lysosomal degradation and, in consequence, modulates epithelial barrier.
25616664 Autophagy reduces the paracellular permeability of small solutes and ions via degradation of the pore-forming tight junction protein claudin-2.
25323998 Claudin-5 overexpression promoted the interactions of claudin-1 and claudin-2 and enhanced the barrier function of retinal cells.
25253127 Single nucleotide polymorphism is associated with the development of alcoholic pancreatitis.
25031428 Claudins 2 and 4 have reciprocal effects on epithelial barrier function, exhibit differential FRAP dynamics, and compete for residency within the tight junction.
24995964 Decreased claudin-2 enhances endothelial barrier function and may play a role in the prolonged survival of patients with Kaposi sarcoma-associated herpesvirus and HIV co-infection.
24907662 Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells.
24907557 Suggest that claudin 2 is involved in paracellular water transport and that claudin 2 expression is sensitive to compound induced cellular stress.
24840331 The exposure to HIV-1 or HIV-1 gp120 results in a significant downregulation of tight junction proteins ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5 in human retinal pigment epithelial cells
24662742 IL-6 modulation of intestinal TJ permeability was regulated by JNK activation of AP-1 and AP-1 activation of claudin-2 gene
24294371 Report altered claudin 1 expression when comparing normal skin to actinic keratosis and squamous cell carcinoma of the skin.
24287398 In breast cancer patients CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites.
24287273 Helicobacter pylori-induced tumorigenesis and invasiveness of gastric carcinoma cells is mediated by bacterial CagA via Cdx2-dependent targeting of Claudin-2.
23946598 Findings suggest that a variant of the CLDN2-MORC4 region predisposes to Crohn's disease in a Swedish population.
23919729 The expression of claudin-2 was down regulated in gastric cancer tissue.
23760508 generated MDCK I Tet-off cells stably transfected with claudin-2 Tyr(67) mutants. The Y67L mutant showed reduced cation selectivity compared with wild-type claudin-2 due to a decrease in Na(+) permeability, without affecting the Cl(-) permeability
23717570 Claudin-2 protein expression is elevated in intestinal epithelia, in response to bovine colostrum, without altering ion permeability.
23306855 Claudin-2 assumes an important role in colorectal inflammation, and furthermore implicates the involvement of MLCK in colon inflammation.
23143602 Two associations with alcoholic pancreatitis at genome-wide significance were identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study.
22946653 results implicate pericryptal myofibroblast-derived paracrine KGF and largely autocrine amphiregulin in the upregulation of claudin-2 in Caco-2 epithelial monolayers and consequent disruption of tight junction integrity
22927233 Sinonasal epithelium in allergic fungal rhinosinusitis displays increased epithelial permeability and an altered expression of claudin-2
22731716 Stable expression of inducible GFP-SUMO-1 in MDCK cells resulted in decreased levels of claudin-2 protein by immunoblot and decreased claudin-2 membrane expression
22546605 These results suggest that EGF is secreted from A549 cells by MMP and increases claudin-2 expression mediated via the activation of an EGFR/MEK/ERK pathway.
21688348 Pore-forming tight junction protein claudin-2 is strongly expressed in the ileum of 51% patients in quiescent phase and in 49% of the patients with active Crohn's disease.
21383692 demonstrate here that breast cancer cells harbouring PIK3CA mutations are selectively sensitive to mTOR allosteric and kinase inhibitors. However, cells with PTEN loss of function are not sensitive to these drugs
21076473 CLDN2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of cell membrane complexes.
20700059 The authors propose claudin-2 and SYN1 work in concert to enhance microbial translocation across the intestinal epithelial barrier to contribute to chronic immune activation and CD4 T-cell depletion in HIV-1-infected patients.
20204275 claudin-2 was not expressed in any of the 18 cases of Epstein-Barr virus-associated nasopharyngeal carcinoma studied.
20143085 CLDN 2 expression was significantly increased in severe form of coeliac disease in bulb and in distal duodenum
20133805 Data show that claudin-2 expression was reduced following symplekin down-regulation, and siRNA-mediated claudin-2 down-regulation increased the transepithelial resistance and decreased cyclin D1 expression and ZONAB nuclear localization.
19214581 The up-regulation of claudin-2 by TNFalpha is attributable to the regulation of the expression of the gene, as a result of which epithelial barrier function is disturbed.
19120888 Up-regulation of claudin-2 might lead to altered tight junction structure and be related to the impaired epithelial function in active ulcerative colitis.
19082451 The expression of claudins-2, -3 and -4 in 16 rectal well-differentiated endocrine neoplasms was studied
18942115 findings are consistent with the hypothesis that EGFR signaling plays an important role in A549 cell physiology and acts synergistically with claudin-2 to accelerate tumor colonizati
18711353 Claudin-1 and claudin-2 expression was elevated in active inflammatory bowel disease (IBD), adenomas, and IBD-associated dysplasia, but not acute self limiting colitis
18602630 These results provide an insight into the changes in the inter-molecular forces and adhesion kinetics of Cldn2 mediated interactions in acidic, neutral and alkaline environments.
18538010 The exposure to HIV-1 or HIV-1 gp120 results in a significant downregulation of tight junction proteins ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5 in human retinal pigment epithelial cells
18509255 The discovery of claudin 2 transcript and protein in the skin could be of importance in epidermal differentiation, barrier function and pathological conditions.
18500171 Significant correlations sre found between claudin-2 and Cdx2 protein expression in dysplasia and intestine-type adenocarcinoma.
18366005 Claudin-2 protein overexpression may be closely correlated to gastric carcinogenesis.
18287530 These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca(2+) channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.
18198187 Expression of claudin-2 results in a selective increase in pore number but not size and has no effect on the permeability of PEGs that are larger than the pores.
17970035 The expression of claudin-1 and claudin-2 in cancer tissues was upregulated 40- and 49.2-fold, respectively, at the mRNA level, as compared with that in normal tissues
17640674 IL-4 and interferon gamma have opposite effects on the expression of claudin-2 and the physiology of the tight junction
17418912 Comparison of adenocarcinomas and squamous cell carcinomas revealed significant differences in CLDN2 expression.
17314274 RT-PCR data show high expression of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues.
17283368 Expression of claudin-2 was increased in acute calculous cholecystitis.
17103306 Claudin tight junction proteins in endoscopy biopsy samples showed Barrett's metaplasia contains more claudin-2 and claudin-3 than found in normal esophageal mucosa, but markedly lower claudins 1 and 5, indicating very different tight junction barriers.
16328347 No obvious correlation was found between claudin-2 expression and clinicopathological parameters of colorectal cancers.
15389642 optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization
14751232 role for the paracellular barrier function by opening pores for small cations
12700140 Results support a model in which claudins 2 and 4 create paracellular channels and the first extracellular domain is sufficient to determine both paracellular charge selectivity and transepithelial electrical resistance.
11934881 Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha.

AA Sequence

MASLGLQLVGYILGLLGLLGTLVAMLLPSWKTSSYVGASIVTAVGFSKGLWMECATHSTGITQCDIYSTL      1 - 70
LGLPADIQAAQAMMVTSSAISSLACIISVVGMRCTVFCQESRAKDRVAVAGGVFFILGGLLGFIPVAWNL     71 - 140
HGILRDFYSPLVPDSMKFEIGEALYLGIISSLFSLIAGIILCFSCSSQRNRSNYYDAYQAQPLATRSSPR    141 - 210
PGQPPKVKSEFNSYSLTGYV                                                      211 - 230
//

Text Mined References (81)

PMID Year Title
26820620 2016 Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis.
26568313 2015 Claudin-2-dependent paracellular channels are dynamically gated.
26212084 2015 Tight junction CLDN2 gene is a direct target of the vitamin D receptor.
26110235 2015 Association of claudin2 and PRSS1-PRSS2 polymorphisms with idiopathic recurrent acute and chronic pancreatitis: A case-control study from India.
26061016 2015 Quercetin Decreases Claudin-2 Expression Mediated by Up-Regulation of microRNA miR-16 in Lung Adenocarcinoma A549 Cells.
26023235 2015 Structural Basis of a Key Factor Regulating the Affinity between the Zonula Occludens First PDZ Domain and Claudins.
25948735 2015 Tumor necrosis factor-? induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions.
25823815 2015 Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis.
25694446 2015 PKC? interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels.
25616664 2015 Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation.
25416956 2014 A proteome-scale map of the human interactome network.
25323998 2014 The effect of claudin-5 overexpression on the interactions of claudin-1 and -2 and barrier function in retinal cells.
25253127 2015 Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study.
25031428 2014 Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins.
24995964 2014 Claudin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function.
24907662 2014 Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.
24907557 2014 Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel.
24662742 2014 Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene.
24294371 2013 Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin.
24287398 2014 Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.
24287273 H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.
23946598 2013 Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease.
23919729 2013 The distinct expression patterns of claudin-2, -6, and -11 between human gastric neoplasms and adjacent non-neoplastic tissues.
23760508 2013 Conserved aromatic residue confers cation selectivity in claudin-2 and claudin-10b.
23717570 2013 Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu.
23677799 2013 Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23306855 2013 Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling.
23143602 2012 Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.
22946653 2012 Myofibroblast keratinocyte growth factor reduces tight junctional integrity and increases claudin-2 levels in polarized Caco-2 cells.
22927233 2013 Epithelial permeability alterations in an in vitro air-liquid interface model of allergic fungal rhinosinusitis.
22731716 2012 SUMOylation of claudin-2.
22546605 2012 Increase in claudin-2 expression by an EGFR/MEK/ERK/c-Fos pathway in lung adenocarcinoma A549 cells.
21688348 2012 Adherent-invasive Escherichia coli induce claudin-2 expression and barrier defect in CEABAC10 mice and Crohn's disease patients.
21383692 2011 Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation.
21076473 2011 Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes.
20700059 2010 A role for syndecan-1 and claudin-2 in microbial translocation during HIV-1 infection.
20204275 2010 Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma.
20143085 2010 Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease.
20133805 2010 Symplekin promotes tumorigenicity by up-regulating claudin-2 expression.
19214581 2009 TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling.
19120888 2008 Changes in the expression of claudins in active ulcerative colitis.
19082451 2009 Claudin expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors).
18942115 2009 Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: implications for non-small cell lung cancer tumor colonization.
18711353 2008 Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation.
18602630 2008 Probing effects of pH change on dynamic response of Claudin-2 mediated adhesion using single molecule force spectroscopy.
18509255 2008 Claudin 2 mRNA and protein are present in human keratinocytes and may be regulated by all-trans-retinoic acid.
18500171 2007 Expression of Cdx2 and claudin-2 in the multistage tissue of gastric carcinogenesis.
18366005 2008 Expression of claudin-2 in the multistage process of gastric carcinogenesis.
18287530 2008 Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes.
18198187 2008 The density of small tight junction pores varies among cell types and is increased by expression of claudin-2.
18036336 2008 Structure and function of claudins.
17970035 Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer.
17640674 2008 Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4.
17418912 2007 Distinct claudin expression profile in histologic subtypes of lung cancer.
17314274 2007 Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer.
17283368 2007 Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis.
17103306 2006 Transepithelial leak in Barrett's esophagus.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16328347 2006 Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas.
16303743 2005 Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15772651 2005 The DNA sequence of the human X chromosome.
15498874 2004 Large-scale cDNA transfection screening for genes related to cancer development and progression.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15389642 2005 Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells.
15070779 2004 Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins.
14751232 2004 Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12975309 2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
12700140 2003 Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12475568 2003 Tight junction proteins.
12231346 2002 Claudin-based barrier in simple and stratified cellular sheets.
11934881 2002 Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha.
11283726 2001 Multifunctional strands in tight junctions.
11247307 2001 The roles of claudin superfamily proteins in paracellular transport.
10690502 2000 Tight junctions of the blood-brain barrier.
10601346 1999 Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins.
9892664 1999 Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands.
9647647 1998 Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin.