Occludin is a transmembrane protein that regulates the permeability of epithelial and endothelial barriers. 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.
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. It belongs to the family of zonula occludens proteins, 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. 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.
Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family.
Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.
Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene. IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.
Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.
Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.
Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the S100A1 gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 has shown promise as an effective candidate for gene therapy to treat post-myocardially infarcted cardiac tissue.
S100 calcium-binding protein A6 (S100A6) is a protein that in humans is encoded by the S100A6 gene.
Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.
Calcium-transporting ATPase type 2C member 1 is an enzyme that in humans is encoded by the ATP2C1 gene.
Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the KCNA2 gene.
S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.
Calcium/calmodulin-dependent protein kinase type II delta chain is an enzyme that in humans is encoded by the CAMK2D gene.
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 is an enzyme that in humans is encoded by the ATP2A3 gene.
F-actin-capping protein subunit alpha-1 is a protein that in humans is encoded by the CAPZA1 gene.
Inositol-trisphosphate 3-kinase A is an enzyme that in humans is encoded by the ITPKA gene.
Macrophage-capping protein (CAPG) also known as actin regulatory protein CAP-G is a protein that in humans is encoded by the CAPG gene.
