Tight junction protein 1

Last updated
TJP1
Protein TJP1 PDB 2h2b.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TJP1 , ZO-1, Tight junction protein 1
External IDs OMIM: 601009 MGI: 98759 HomoloGene: 2445 GeneCards: TJP1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001163574
NM_009386

RefSeq (protein)

NP_001157046
NP_033412

Location (UCSC) Chr 15: 29.7 – 29.97 Mb Chr 7: 65.3 – 65.53 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zonula occludens-1 ZO-1, also known as Tight junction protein-1 is a 220-kD peripheral membrane protein that is encoded by the TJP1 gene in humans. [5] It belongs to the family of zonula occludens proteins (ZO-1, ZO-2, and ZO-3), which are tight junction-associated proteins and of which, ZO-1 is the first to be cloned. It was first isolated in 1986 by Stevenson and Goodenough using a monoclonal antibody raised in rodent liver to recognise a 225-kD polypeptide in whole liver homogenates and in tight junction-enriched membrane fractions. [6] It has a role as a scaffold protein which cross-links and anchors Tight Junction (TJ) strand proteins, which are fibril-like structures within the lipid bilayer, to the actin cytoskeleton. [7]

Function

This gene encodes a protein located on a cytoplasmic membrane surface of intercellular tight junctions. The encoded protein may be involved in signal transduction at cell–cell junctions. Two transcript variants encoding distinct isoforms have been identified for this gene. [8]

Interactions

Tight junction protein 1 has been shown to interact with:

See also

Related Research Articles

Tight junction

Tight junctions, also known as occluding junctions or zonulae occludentes are multiprotein junctional complexes whose general function is to prevent leakage of transported solutes and water and seals the paracellular pathway. Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. Tight junctions are present mostly in vertebrates. The corresponding junctions that occur in invertebrates are septate junctions.

Adherens junction

Adherens junctions are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell or as spots of attachment to the extracellular matrix . Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells.

Beta-catenin

Catenin beta-1, also known as β-catenin, is a protein that in humans is encoded by the CTNNB1 gene.

Occludin Mammalian protein found in Homo sapiens

Occludin is an enzyme that oxidizes NADH. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with Claudins, and zonula occludens-1 (ZO-1), occludin has been considered a staple of tight junctions, and although it was shown to regulate the formation, maintenance, and function of tight junctions, its precise mechanism of action remained elusive and most of its actions were initially attributed to conformational changes following selective phosphorylation, and its redox-sensitive dimerization. However, mounting evidence demonstrated that occludin is not only present in epithelial/endothelial cells, but is also expressed in large quantities in cells that do not have tight junctions but have very active metabolism: pericytes, neurons and astrocytes, oligodendrocytes, dendritic cells, monocytes/macrophages lymphocytes, and myocardium. Recent work, using molecular modeling, supported by biochemical and live-cell experiments in human cells demonstrated that occludin is a NADH oxidase that influences critical aspects of cell metabolism like glucose uptake, ATP production and gene expression. Furthermore, manipulation of occludin content in human cells is capable of influencing the expression of glucose transporters, and the activation of transcription factors like NFkB, and histone deacetylases like sirtuins, which proved capable of diminishing HIV replication rates in infected human macrophages under laboratory conditions.

Alpha catenin

Alpha-catenin functions as the primary protein link between cadherins and the actin cytoskeleton. It has been reported that the actin binding proteins vinculin and alpha-actinin can bind to alpha-catenin. It has been suggested that alpha-catenin does not bind with high affinity to both actin filaments and the E-cadherin-beta-catenin complex at the same time. It has been observed that when alpha-catenin is not in a molecular complex with beta-catenin, it dimerizes and functions to regulate actin filament assembly, possibly by competing with Arp2/3 protein. Alpha catenin exhibits significant protein dynamics.

Afadin

Afadin is a protein that in humans is encoded by the AFDN gene.

CLDN1

Claudin-1 is a protein that in humans is encoded by the CLDN1 gene. It belongs to the group of claudins.

Tight junction protein 2

Tight junction protein ZO-2 is a protein that in humans is encoded by the TJP2 gene.

CLDN4

Claudin 4, also known as CLDN4, is a protein which in humans is encoded by the CLDN4 gene. It belongs to the group of claudins.

F11 receptor

Junctional adhesion molecule A is a protein that in humans is encoded by the F11R gene. It has also been designated as CD321.

CLDN5

Claudin-5 is a protein that in humans is encoded by the CLDN5 gene. It belongs to the group of claudins.

CLDN3

Claudin 3, also known as CLDN3, is a protein which in humans is encoded by the CLDN3 gene. It is a member of the claudin protein family.

CLDN2

Claudin-2 is a protein that in humans is encoded by the CLDN2 gene. It belongs to the group of claudins.

Cingulin

Cingulin is a cytosolic protein encoded by the CGN gene in humans localized at tight junctions (TJs) of vertebrate epithelial and endothelial cells.

Stress fiber contractile actin bundles found in non-muscle cells

Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated actomyosin structure within non-muscle cells. Stress fibers have been shown to play an important role in cellular contractility, providing force for a number of functions such as cell adhesion, migration and morphogenesis.

CDH1 (gene) Human protein-coding gene

Cadherin-1 also known as CAM 120/80 or epithelial cadherin (E-cadherin) or uvomorulin is a protein that in humans is encoded by the CDH1 gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324. It is a tumor suppressor gene.

Catenin alpha-1

αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene. αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of actin filaments to the sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function.

TLN1

Talin-1 is a protein that in humans is encoded by the TLN1 gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of integrins to the actin cytoskeleton and in the activation of integrins. Altered expression of talin-1 has been observed in patients with heart failure, however no mutations in TLN1 have been linked with specific diseases.

TJP3

Tight junction protein ZO-3 is a protein that in humans is encoded by the TJP3 gene.

Cingulin-like protein 1

Cingulin-like protein 1, also known as paracingulin or junction-associated-coiled-coil protein (JACOP), is a protein which is encoded by the CGNL1 gene.

References

  1. 1 2 3 ENSG00000104067 GRCh38: Ensembl release 89: ENSG00000277401, ENSG00000104067 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030516 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Mohandas TK, Chen XN, Rowe LB, Birkenmeier EH, Fanning AS, Anderson JM, Korenberg JR (December 1995). "Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7". Genomics. 30 (3): 594–7. doi:10.1006/geno.1995.1281. PMID   8825647.
  6. Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA (September 1986). "Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia". The Journal of Cell Biology. 103 (3): 755–66. doi:10.1083/jcb.103.3.755. PMC   2114282 . PMID   3528172.
  7. Itoh M, Nagafuchi A, Moroi S, Tsukita S (July 1997). "Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments". The Journal of Cell Biology. 138 (1): 181–92. doi:10.1083/jcb.138.1.181. PMC   2139940 . PMID   9214391.
  8. "Entrez Gene: TJP1 tight junction protein 1 (zona occludens 1)".
  9. Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D (Sep 2000). "Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1". The Journal of Biological Chemistry. 275 (36): 27979–88. doi: 10.1074/jbc.M002363200 . PMID   10856295.
  10. Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyer zu Brickwedde MK, Suzuki A, Imhof BA, Vestweber D (Oct 2003). "The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity". Journal of Cell Science. 116 (Pt 19): 3879–91. doi: 10.1242/jcs.00704 . PMID   12953056.
  11. 1 2 Nielsen PA, Baruch A, Shestopalov VI, Giepmans BN, Dunia I, Benedetti EL, Kumar NM (Jun 2003). "Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1)". Molecular Biology of the Cell. 14 (6): 2470–81. doi:10.1091/mbc.E02-10-0637. PMC   194895 . PMID   12808044.
  12. Giepmans BN, Moolenaar WH (1998). "The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein". Current Biology. 8 (16): 931–4. doi: 10.1016/S0960-9822(07)00375-2 . PMID   9707407.
  13. Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS (Jul 2003). "Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability". The Journal of Clinical Investigation. 112 (2): 209–21. doi:10.1172/JCI18242. PMC   164293 . PMID   12865409.
  14. Huber TB, Schmidts M, Gerke P, Schermer B, Zahn A, Hartleben B, Sellin L, Walz G, Benzing T (Apr 2003). "The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1". The Journal of Biological Chemistry. 278 (15): 13417–21. doi: 10.1074/jbc.C200678200 . PMID   12578837.
  15. Yamamoto T, Harada N, Kawano Y, Taya S, Kaibuchi K (May 1999). "In vivo interaction of AF-6 with activated Ras and ZO-1". Biochemical and Biophysical Research Communications. 259 (1): 103–7. doi:10.1006/bbrc.1999.0731. PMID   10334923.
  16. 1 2 Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (Nov 1998). "The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton". The Journal of Biological Chemistry. 273 (45): 29745–53. doi: 10.1074/jbc.273.45.29745 . PMID   9792688.
  17. Rao RK, Basuroy S, Rao VU, Karnaky Jr KJ, Gupta A (Dec 2002). "Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress". The Biochemical Journal. 368 (Pt 2): 471–81. doi:10.1042/BJ20011804. PMC   1222996 . PMID   12169098.
  18. 1 2 Wittchen ES, Haskins J, Stevenson BR (Dec 1999). "Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3". The Journal of Biological Chemistry. 274 (49): 35179–85. doi: 10.1074/jbc.274.49.35179 . PMID   10575001.
  19. Itoh M, Morita K, Tsukita S (Feb 1999). "Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin". The Journal of Biological Chemistry. 274 (9): 5981–6. doi: 10.1074/jbc.274.9.5981 . PMID   10026224.

Further reading