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FLASH GENE

Symbol

TJP2

contributors: mct/npt/pgu - updated : 13-01-2014

HGNC name	tight junction protein 2 (zona occludens 2)
HGNC id	11828

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DFNA51 neurosensory deafness 51
Location	9q21.11      Physical location : 71.736.223 - 71.870.124
Synonym name	Friedreich ataxia region gene X104 (tight junction protein ZO-2)
	zonula occludens protein 2
Synonym symbol(s)	ZO2, X104, ZO-2, MGC26306

DNA

TYPE	functioning gene
STRUCTURE	155.25 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004817 23 - 4725 NP_004808 133 1190 . abundant in the heart and brain . in brain and skeletal muscle, only this isoform is detectable . present almost exclusively in normal tissue . downregulated in several breast adenocarcinomas and breast cancer cell lines and in pancreatic adenocarcinoma of the ductal type 2000 11018256 transcribed from promoter A 23 exons NM_201629 20 splicing 4228 NP_963923 117 1043 - 2000 11018256 transcribed from promoter A alternatively spliced transcript with in-frame skipping of exons 20 and 21, resulting in a protein that lacks 147 amino acids in the C-terminal region (21 exons) variant A3 - splicing - isoform A3 - 993 - 2000 11018256 transcribed from promoter A variant C1 - - - isoform C1 - 1167 . high level in the kidney, pancreas, heart and placenta . found in normal as well as in most neoplastic tissues 2000 11018256 transcribed from promoter C lacking an N-terminal 23-amino acid peptide present in variant A variant C2 - splicing - isoform C2 - 1019 - 2000 11018256 transcribed from promoter C lacking an N-terminal 23-amino acid peptide present in variant A NM_001170414 22 - 4129 NP_001163885 - 1020 - - NM_001170630 19 - 4720 NP_001164101 - 993 - - NM_001170415 22 - 4459 NP_001163886 - 1157 - - NM_001170416 23 - 4500 NP_001163887 - 1221 - -

EXPRESSION

Type

widely

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 Cardiovascular vessels capillary     highly Digestive intestine large intestine colon   highly   stomach       highly Endocrine parathyroid       highly   thyroid       highly Hearing/Equilibrium ear inner     highly Respiratory respiratory tract trachea     highly Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining endothelium     Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol   epithelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three copies of a PDZ domain with slight divergence acting as protein-recognition modules that may mediate protein assembly and subunit localization
	a SH3 domain
	a guanylate kinase-like domain

conjugated

PhosphoP

HOMOLOGY

interspecies

ortholog to murine Tjp2 (86.2pc)

Homologene

FAMILY

MAGUK (membrane-associated guanylate kinase homolog) superfamily

CATEGORY

adhesion , chaperone/stress , structural protein

SUBCELLULAR LOCALIZATION	plasma membrane,junction,tight
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	peripheral membrane
	cytoplasmic side
	nuclear under environmental stress conditions and in migratory endothelial cells and subconfluent epithelial cell cultures
	in the mammalian inner ear, TJP2 is expressed mainly in tight junctions, and also in the cytoplasm and nuclei
	TJP2 and YAP1 proteins co-localize in the nucleus
	not exclusively expressed in epithelia and endothelia but is also found in other cell types lacking tight junctions
	present at the tight junction and nucleus of epithelial cells

basic FUNCTION	F actin filament binding scaffold protein
	structural component of tight junction and adherens junction
	acting as a guanylate kinase
	may serve to anchor regulatory proteins at gap junctions composed of GJD2
	exerts a junction-unrelated function, supporting the notion of a general "dual" role of junctional MAGUKs, being an indispensable structural component at cell-cell junctions and a nuclear factor influencing gene expression and cell behavior
	can control the subcellular location of TAZ
	facilitates the nuclear localization and pro-apoptotic function of YAP1, and this activity is PDZ-domain-dependent
	scaffold molecule possessing several specific domains organizing multimeric complexes with both signaling and structural functions
	mediates specific homotypic cell-to-cell contacts between vascular smooth muscle cells
	may play a more general role in organizing functional protein complexes and in recruiting signaling molecules that regulate intercellular communication through tight junction independent mechanisms
	TJP1 and TJP2 are required not only for TJ assembly but also for regulating the organization and functional activity of the apical cytoskeleton, particularly the perijunctional actomyosin ring
	represses the transcription of genes regulated by the Wnt/CTNNB1 pathway

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	bind to the C-terminus of OCLN
	TJP1
	F-actin skeleton
	alpha catenin
	SAFB
	interacting with ANGPT1 (have anti-permeability activity through up-regulation of TJP2)
	associating directly with the C terminus of claudins
	direct binding to scaffold attachment factor B, a heterogeneous nuclear ribonucleoprotein involved in chromatin organization and the transcriptional control of eukaryotic genes
	interacting with GSK3B (TJP2 overexpression results in changes in GSK3B phosphorylation and apoptosis-related gene expression and these changes increase the susceptibility of inner ear cells to apoptosis)
	interaction between TAZ and TJP1, TJP2, through TAZ C-terminal PDZ binding motif
	uses its first PDZ domain to form a complex with YAP1
	associates with JAK1 in vascular smooth muscle cells via TJP2 N-terminal fragment and JAK1 serves for tyrosine phosphorylation of TJP2 in VSMC
	AMOTL1 inhibits pro-apoptotic function of YAP1, whereas TJP2 enhances it
	LASP1-binding partner, TJP2, having a role in the signal transduction pathway of LASP1 nucleo-cytoplasmatic shuttling
	SNX27-TJP2 interaction requires the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of TJP2 (role for SNX27-TJP2 interactions in tight junction maintenance and function)
	F11R associates directly with TJP2 and indirectly with afadin, and this complex, along with RAPGEF2, activates the small GTPase RAP2C

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DFNA51

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in familial hypercholanemia tumoral         in pancreatic adenocarcinoma, breast adenocarcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     networking between TAZ and TJP1 and TJP2 offers a promising target in the control of proliferation and apoptosis, epithelial-mesenchymal transition and migration capacity of cancer cells cancer     YAP1-TJP2 complex could represent a target for cancer therapy

ANIMAL & CELL MODELS