Available structures
PDBOrtholog search: PDBe RCSB
AliasesOCLN, BLCPMG, PPP1R115, occludin, PTORCH1
External IDsOMIM: 602876 MGI: 106183 HomoloGene: 1905 GeneCards: OCLN
RNA expression pattern
HumanMouse (ortholog)
Top expressed in
Top expressed in
More reference expression data
View/Edit HumanView/Edit Mouse
Diagram of Tight junction.
Diagram of Tight junction.

Occludin is an enzyme (EC 1.6) that oxidizes NADH.[5] It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions.[6] 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,[7] and its redox-sensitive dimerization.[8][9] 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,[5] neurons and astrocytes,[10] oligodendrocytes,[11] dendritic cells,[12] monocytes/macrophages[13] lymphocytes,[14] and myocardium.[15] 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.[16] Furthermore, manipulation of occludin content in human cells is capable of influencing the expression of glucose transporters,[16] 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.[5]

Gene location

In humans is encoded by the OCLN gene[17][18] located on the long (q) arm of chromosome 5 at position q13.1. The canonical gene is 65,813 base pairs long, spanning base pairs 69,492,292 to 69,558,104.[19] Its product is 522 amino acids long.

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:

The C-terminus domain has been shown experimentally to be required for correct assembly of tight junction barrier function.[20] The C-terminus also interacts with several cytoplasmic proteins of the junctional plaque and interacts with signaling molecules responsible for cell survival.[21] The N-terminus of occludin experimentally has been linked to involvement in tight junction sealing/barrier properties.[21] 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.[21]


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. Indeed, MDCK cells lacking occludin and its homolog tricellulin exhibit less complex tight junction strand network and impaired barrier function.[22] 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.[23]

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.[24]

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.[25] 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.[26]

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.


Occludin has been shown to interact with Tight junction protein 2,[27][28][29] YES1[30] and Tight junction protein 1 (ZO-1).[31][32]


  1. ^ a b c ENSG00000273814 GRCh38: Ensembl release 89: ENSG00000197822, ENSG00000273814 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021638 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  18. ^ "Entrez Gene: OCLN occludin".
  19. ^ "OCLN occludin [Homo sapiens (human)] - Gene - NCBI".
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  27. ^ 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. S2CID 33062461.
  28. ^ 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. PMID 10026224. S2CID 20269381.
  29. ^ 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. PMID 10575001. S2CID 23928833.
  30. ^ 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. PMC 102264. PMID 11950934.
  31. ^ 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. PMID 9792688. S2CID 23935899.
  32. ^ 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. PMC 1222996. PMID 12169098.

Further reading