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RefSeq (mRNA)



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Occludin is a protein that in humans is encoded by the OCLN gene.[1][2] Occludin is a 65-kDa (522-amino acid polypeptide -human) integral plasma-membrane protein located at the tight junctions, described for the first time in 1993 by Shoichiro Tsukita.[3] Together with the Claudin group of proteins, it is the main component of the tight junctions.

Gene location

The OCLN gene is located on the long (q) arm of chromosome 5 at position q13.1. The gene starts at base pair 69,492,292 and goes to base pair 69,558,104 and is 65,813 base pairs long.[4]

Protein structure

Occludin's structure can be broken down into 9 domains. These domains are separated into two groups. 5 of the domains are located intracellularly and extracellularly. These 5 domains are separated by the 4 transmembrane domains of the protein. The nine domains are as follows:

  • N-terminus domain (66 aa)
  • transmembrane domain 1 (23 aa)
  • extracellular loop 1 (46 aa)
  • transmembrane domain 2 (25 aa)
  • intracellular loop (10 aa)
  • transmembrane domain 3 (25 aa)
  • extracellular domain 2 (48 aa)
  • transmembrane domain 4 (22 aa)
  • C-terminus domain (257 aa)

The C-terminus domain has been shown experimentally to be required for correct assembly of tight junction barrier function.[5] The C-terminus also interacts with several cytoplasmic proteins of the junctional plaque and interacts with signaling molecules responsible for cell survival.[6] The N-terminus of occludin experimentally has been linked to involvement in tight junction sealing/barrier properties.[6] The extracellular loops are thought to be involved in the regulation of paracellualr permeability and the second extracellular has been shown to be involved in the localization of occludin at the tight junction.[6]


Occludin is an important protein in tight junction function. Studies have shown that rather than being important in tight junction assembly, occludin is important in tight junction stability and barrier function. Furthermore, studies in which mice were deprived of occludin expression showed morphological stability in several epithelial tissues but also found chronic inflammation and hyperplasia in the gastric epithelium, calcification in the brain, testicular atrophy, loss of cytoplasmic granules in straited duct cells of salivary gland, and thinning of the compact bone. The phenotypical response of these mice to the lack of occludin suggest that the function of occludin is more complex than thought and requires more work.[7]

Role in cancer

Occludin plays a critical role in maintaining the barrier properties of a tight junction. Thus, mutation or absence of occludin increases epithelial leakiness which is an important barrier in preventing metastasis of cancer. Loss of occludin or abnormal expression of occludin has been shown to cause increased invasion, reduced adhesion and significantly reduced tight junction function in breast cancer tissues. Furthermore, patients with metastatic disease displayed significantly lower levels of occludin suggesting that the loss of occludin and thereby loss of tight junction integrity is important in metastatic development of breast cancer.[8]

Occludin also plays an important role in the apoptosis. The C-terminus of occludin is important in receiving and transmitting cell survival signals. In standard cells, loss or disruption of occludin and other tight junction proteins leads to initiation of apoptosis through extrinsic pathways.[9] Studies involving high levels of expression of occludin in cancer cells have shown that occludin mitigates several important cancer proliferation properties. The presence of occludin decreased cellular invasiveness and motility, enhanced cellular sensitivity to apoptogenic factors and lowered tumorigenesis and metastasis of the cancer cells. Specifically, occludin has a strong inhibitory effect on Raf1-induced tumorigenesis. Still, the exact mechanism of how occludin prevents the progression of cancer is not known but it has been shown that cancer progression is linked to the loss of occludin or the silencing of the OCLN gene.[10]

Disease linkage

Disruption of occludin regulation is an important aspect of a number of diseases. Strategies to prevent and/or reverse occludin downregulation may be an important therapeutic target. Mutation of occludin are thought to be a cause of band-like calcification with simple gyration and polymicrogyria (BLC-PMG). BLC-PMG is an autosomal recessive neurologic disorder.

File:Cellular tight junction-en.svg
Diagram of Tight junction.


Occludin has been shown to interact with Tight junction protein 2,[11][12][13] YES1[14] and Tight junction protein 1.[15][16]


  1. Ando-Akatsuka Y, Saitou M, Hirase T, Kishi M, Sakakibara A, Itoh M, Yonemura S, Furuse M, Tsukita S (May 1996). "Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues". J Cell Biol. 133 (1): 43–47. doi:10.1083/jcb.133.1.43. PMC 2120780. PMID 8601611.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. "Entrez Gene: OCLN occludin".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993). "Occludin: a novel integral membrane protein localizing at tight junctions". J. Cell Biol. 123 (6 Pt 2): 1777–1788. doi:10.1083/jcb.123.6.1777. PMC 2290891. PMID 8276896.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. https://www.ncbi.nlm.nih.gov/gene/100506658
  5. Chen Y, Merzdorf C, Paul DL, Goodenough DA (August 1997). "COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos". The Journal of Cell Biology. 138 (4): 891–9. doi:10.1083/jcb.138.4.891. PMC 2138038. PMID 9265654.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. 6.0 6.1 6.2 Feldman GJ, Mullin JM, Ryan MP (April 2005). "Occludin: structure, function and regulation". Advanced Drug Delivery Reviews. 57 (6): 883–917. doi:10.1016/j.addr.2005.01.009. PMID 15820558.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (December 2000). "Complex phenotype of mice lacking occludin, a component of tight junction strands". Molecular Biology of the Cell. 11 (12): 4131–42. doi:10.1091/mbc.11.12.4131. PMC 15062. PMID 11102513.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. Martin TA, Mansel RE, Jiang WG (November 2010). "Loss of occludin leads to the progression of human breast cancer". International Journal of Molecular Medicine. 26 (5): 723–34. doi:10.3892/ijmm_00000519. PMID 20878095.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  9. Beeman N, Webb PG, Baumgartner HK (February 2012). "Occludin is required for apoptosis when claudin-claudin interactions are disrupted". Cell Death & Disease. 3: e273. doi:10.1038/cddis.2012.14. PMC 3288343. PMID 22361748.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  10. Osanai M, Murata M, Nishikiori N, Chiba H, Kojima T, Sawada N (September 2006). "Epigenetic silencing of occludin promotes tumorigenic and metastatic properties of cancer cells via modulations of unique sets of apoptosis-associated genes". Cancer Research. 66 (18): 9125–33. doi:10.1158/0008-5472.CAN-06-1864. PMID 16982755.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  11. Peng BH, Lee JC, Campbell GA (December 2003). "In vitro protein complex formation with cytoskeleton-anchoring domain of occludin identified by limited proteolysis". The Journal of Biological Chemistry. 278 (49): 49644–51. doi:10.1074/jbc.M302782200. PMID 14512431.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  12. Itoh M, Morita K, Tsukita S (February 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. ISSN 0021-9258. PMID 10026224.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  13. Wittchen ES, Haskins J, Stevenson BR (December 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. ISSN 0021-9258. PMID 10575001.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  14. Chen YH, Lu Q, Goodenough DA, Jeansonne B (April 2002). "Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells". Molecular Biology of the Cell. 13 (4): 1227–37. doi:10.1091/mbc.01-08-0423. ISSN 1059-1524. PMC 102264. PMID 11950934.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  15. Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (November 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. ISSN 0021-9258. PMID 9792688.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  16. Rao RK, Basuroy S, Rao VU, Karnaky KJ, Gupta A (December 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. ISSN 0264-6021. PMC 1222996. PMID 12169098.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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External links