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FLASH GENE

Symbol

CLDN2

contributors: mct/npt/pgu - updated : 21-07-2015

HGNC name	claudin 2
HGNC id	2041

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	Xq22.3      Physical location : 106.143.393 - 106.174.091
Synonym symbol(s)	SP82

DNA

TYPE	functioning gene
STRUCTURE	10.46 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site   transcription factor
text structure	binding sites for CDX1, CDX2 hepatocyte nuclear factor alpha
	promoter activity is increased by IL6 in a MEK/ERK and PI3K-dependent manner, and deletion of Cdx binding sites in the promoter sequence results in a loss of IL6-induced promoter activity

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - DXS8048 - DXS8097 - CLDN2 - DXS1504 - DXS7677 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001171092 2 - 3163 NP_001164563 24.4 230 - 2008 18509255 NM_138382 4 - 1206 NP_612391 - 151 - 2008 18509255 NM_001171706 2 - 1065 NP_001165177 - 104 - 2008 18509255

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine         Hearing/Equilibrium ear inner cochlea       ear inner vestibule     Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining epidermis stratum granulosum

cells

System Cell Pubmed Species Stage Rna symbol not specific granular cell Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , dimer

HOMOLOGY

interspecies

ortholog to murine Cldn2

Homologene

FAMILY

claudin family

CATEGORY

adhesion , structural protein

SUBCELLULAR LOCALIZATION

plasma membrane,junction,tight

basic FUNCTION	tight junction specific obliteration of the intercellular space
	creating charge specific channels in the paracellular space
	Ca2+ independent cell adhesion activity
	critical role for vitamin D-dependent Ca2+ absorption between enterocytes
	forms a cation-selective channel which confers increased permeability in renal epithelial cells and in the intestine where its expression is restricted to the leaky epithelium (
	forms highly cation-selective paracellular pores (
	essential mediator in the tumor-promoting role of symplekin
	role for claudin-2 in promoting colon cancer, potentially via EGFR transactivation
	potential functions that are relevant to neoplastic transformation and growth
	functional mediator of breast cancer liver metastasis
	promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes
	regulates colorectal inflammation via MYLK

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	major structural components of tight junction (TJ) strands
	dimerization does not require the cytoplasmic or extracellular domains and is likely mediated through interaction of one or several of its four transmembrane segments

INTERACTION

DNA

RNA

small molecule

protein	EGF controls the levels of CLDN2 and CLDN4 proteins and mRNAs through SRC and STAT3 activity
	IL22 increases intestinal epithelial permeability by upregulating CLDN2 expression through the JAK/STAT pathway

cell & other

REGULATION

activated by

all-trans-retinoic acid (increases the expression of claudin 2 in keratinocytes in a dose-dependent manner)

induced by

IL6 (markedly induces claudin-2 expression, which is associated with increased TJ permeability)

Other

regulated by SYMPK that depends on its functional interaction with CSDA

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in breast carcinoma tumoral     --over   may be involved at early stages of transformation in inflammatory bowel disease -associated neoplasia tumoral     --over   may be closely correlated to gastric carcinogenesis constitutional     --low   in renal epithelial cells by metabolic acidosis tumoral     --over   in solar keratosis and skin squamous cell carcinomas compared to normal skin

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS