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FLASH GENE

Symbol

TJP1

contributors: mct/npt/pgu - updated : 15-06-2016

HGNC name	tight junction protein 1 (zona occludens 1)
HGNC id	11827

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	15q13.1      Physical location : 29.992.358 - 30.114.706
Synonym name	zonula occludens 1 protein
	tight junction protein ZO-1
Synonym symbol(s)	ZO1, ZO-1, MGC133289, DKFZp686M05161

DNA

TYPE	functioning gene
STRUCTURE	122.35 kb     28 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - PWCR1 - TJP1 - qter
Authors	PMID: 8825647

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003257 28 - 7165 NP_003248 - 1748 - 1993 8395056 NM_175610 27 - 6925 NP_783297 - 1668 - 1993 8395056

EXPRESSION

Type	ubiquitous

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 heart         Digestive mouth       highly   stomach       highly Nervous nerve cranial nerve     highly Reproductive male system testis       Respiratory respiratory tract larynx     highly Urinary kidney nephron renal capsule glomerulus

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Skin/Tegument hair follicle cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal (MAGUK-like),three Dlg,(DHR/GLGZ/PDZ) motifs, which are necessary for its function and playing a central role in assembling diverse protein complexes through their ability to recognize short peptide motifs on other proteins (PDZ2 domain binding to GJA1)
	a SH3 domain
	a unique proline-rich region cosedimenting with F-actin (ABR,
	actin-binding region), a 220-AAs domain within the C-terminal half, mediating association with actin, at least in part

HOMOLOGY

interspecies	homolog to yeast guanylate kinase
	homolog to Drosophila lethal discs large tumor suppressor protein

Homologene

FAMILY

MAGUK (membrane-associated guanylate kinase homolog) family

CATEGORY

adhesion , chaperone/stress , structural protein

SUBCELLULAR LOCALIZATION	plasma membrane,junction,tight
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	co-localized with JAM3 to adherens-like junctions
	glomeruli predominantly to points where the slit diaphragm is inserted into the lateral cell membrane of the foot process
	SYMPK co-localized with TJP1 at tight junctions

basic FUNCTION	F actin filament binding scaffold protein
	structural component of tight junction and adherens junction
	SHROOM2 and TJP1 form a tight-junction-associated scaffolding complex, possibly linked to myosin VIIa, that bridges the junctional membrane to the underlying cytoskeleton, thereby contributing to the stabilization of these junctions
	colocalised in the salivary excretory ducts with CLDN16 and occludin suggesting a potential role in paracellular calcium and magnesium transport
	central player in the control of gap junction (GJ) dynamics
	regulates GJA1-mediated gap junctional communication in osteoblastic cells and alters the membrane localization of GJA1
	essential for cytoskeletally-mediated barrier regulation
	TJP1 and PLEKHA7 are paracingulin-interacting proteins that are involved in its recruitment to epithelial tight and adherens junctions, respectively
	is a response protein to inner medullary tonicity and extracellular stressors can promote TJP1 protein expression, tyrosine phosphorylation and cytoskeleton association
	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
	CPEB1-mediated TJP1 mRNA localization is essential for tight-junction assembly and mammary epithelial cell polarity
	VCL and TJP1 anchor the actin cytoskeleton to the sarcolemma

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

ABCB1 and an integrated component of the occludin/zonula occludens 1 (TJP1) adhesion complex at the BTB, structurally interacted with PTK2, creating the OCLN/TJP1/PTK2/ABCB1 regulatory complex

INTERACTION

DNA

RNA

small molecule

protein	binding directly to the C terminus of claudins
	binding to occludin and alpha catenin
	associating with F-actin (playing a role in several different steps of junction assembly)
	bind to the C-terminus of OCLN
	interaction with OCLN and PTPRJ specific (OCLN and TJP1 were dephosphorylated by PTPRJ but not the other phosphatases)
	targets to gap junction edges independently of several known PDZ2-mediated interactions, including TJP1 homodimerization, heterodimerization with TJP2, and direct TJP1 binding to the C-terminal residues of GJA1) (H
	by interacting with GJA1, plays a role in the down-regulation and decreased size of GJA1 gap junctions in congestive heart failure
	interacting with KIRREL (tyrosine phosphorylation of KIRREL results in significantly increased KIRREL and TJP1 binding, suggesting a critical role for KIRREL tyrosine phosphorylation in reorganizing the KIRREL-TJP1 complex)
	interacting with MYLK (MYLK activity is critical to TJP1, but not claudin-1, occludin, or actin) exchange at the tight junction)
	interaction between TAZ and TJP1, TJP2, through TAZ C-terminal PDZ binding motif
	TJP1 and the adherens junction protein PLEKHA7 as paracingulin-binding proteins
	GJA8 requires an intact PDZ-binding motif and TJP1 for the formation of functional intercellular channels
	interaction with UBN1 (N-terminal domains of the UBN1 and TJP1 proteins triggered a functional interaction inside the cell)
	ARHGEF11 associates with tight junctions (TJs) by binding to TJP1, in polarized epithelial cells
	KLF4 regulates blood-tumor barrier permeability via TJP1, OCLN and CLDN5
	direct interaction between VCL and TJP1, illustrating how VCL plays a crucial role in stabilizing gap junctions and myocyte integrity
	CALCR interacts with zonula occludens 1 (TJP1) through PDZ interaction to destabilize tight junctions and increase invasion of prostate cancers (PCs) cells

cell & other

REGULATION

Other	upregulated, phosphorylated and linked to the actin cytoskeleton in response to hypertonic stress (

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in patients with heart failure, with diminished expression levels of GJA1, suggesting that TJP1 plays an important role in gap junction formation and gap junction plaque stability constitutional     --other   present in apical tight junctions in normal epithelium but were dislocated to the basolateral position in patients with inactive Crohn disease (

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 reproductive prostate prevention of CALCR-TJP1 interaction abolishes calcitonin-induced invasion, and can serve as a novel therapeutic tool to treat aggressive prostate cancers

ANIMAL & CELL MODELS