This entry includes transmembrane glycoprotein EpCAM (epithelial cell adhesion molecule, also known as Trop-1) and Trop-2 (also known as tumor-associated calcium signal transducer 2, TACSTD2). They belong to the tumour-associated calcium signal transducer (TACSTD) family. They have been reported to directly interact with claudin-1 and claudin-7 [, , ]. EpCAM mediates homotypic cell contacts in epithelia tissues and regulates cell proliferation and cancer stemness. It has been used as a diagnostic marker for circulating tumour cells (CTCs) in the blood []. EpCAM has been shown to contribute to formation of intestinal barrier by recruiting claudins to cell-cell junctions []. Mutations in the EpCAM gene lead to congenital tufting enteropathy, severe intestinal epithelium homeostasis disorders, and Lynch syndrome []. Trop-2 is highly expressed in a variety of epithelial cancer cells. It has been identified as an oncogene leading to invasiveness and tumorigenesis []. It has been shown to regulate integrin-dependent signalling for cell-substrate adhesion and cell migration. It also modulates Rac1 GTPase activity and induces activation of PAK4 [].
EpCAM (epithelial cell adhesion molecule), a stem and carcinoma cell marker, is a cell surface protein involved in homotypic cell-cell adhesion via intercellular oligomerization and proliferative signalling via proteolytic cleavage. Structure analysis indicate that it is composed of three domains: N-terminal domain, Thyroglobulin type-1A (TY) domain and the C-terminal domain. This entry represents the small and compact disulphide-rich N-terminal domain of 39 amino-acid residues [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-10 was identified through cDNA database searching, pursuingsequences similar to other claudin family members []. Human and mouseisoforms have been cloned. Claudin-10 shares ~20-45% overall similarity withother claudin family members at the amino acid level, displaying highestsimilarity to claudin-15.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-14 was identified through cDNA database searching, pursuingsequences similar to other claudin family members []. Human and mouseisoforms have been cloned. Claudin-14 shares ~25-45% overall similarity withother claudin family members at the amino acid level, displaying highestsimilarity to claudin-4.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-4 was originally termed Clostridium perfringens enterotoxin receptor (CPE-R). It was reclassified as claudin-4 on the basis of cDNA sequence similarity with claudins-1 and -2, and antibody studies thatshowed it to be expressed at tight junctions [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-9 was identified through cDNA database searching, pursuing sequencessimilar to other claudin family members []. Human and mouse isoforms havebeen cloned. Claudin-9 shares ~25-70% overall similarity with other claudinfamily members at the amino acid level, displaying highest similarity toclaudin-6.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-7 was identified through searching expressed sequence tag (EST)databases for sequences similar to claudin-1 and -2. It was subsequently cloned and expressed in cells, where it was shown toconcentrate at tight junctions [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-1 was the first member of the claudin family to be identified asa tight junction component []. The human isoform of claudin-1 was originally termed senescence-associated epithelial membrane protein 1 (SEMP1) [], but has since been reclassified.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B andtheir receptors, EphA and EphB [].Claudin-3 was originally termed rat ventral prostate 1 protein (RVP1), andClostridium perfringens enterotoxin receptor 2 (CPETR2). It was reclassified as claudin-3 on the basis of cDNA similarity with claudins-1 and-2, and antibody studies that showed it to be expressed at tight junctions[].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Human and mouse isoforms of claudin-18 have been cloned. Claudin-18 shares~22-40% overall similarity with other claudin family members at the aminoacid level, displaying highest similarity to claudin-1.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Human and mouse isoforms of claudin-15 have been cloned. Claudin-15 shares~25-45% overall similarity with other claudin family members at the aminoacid level, displaying highest similarity to claudin-10.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-2 was initially isolated as a peptide fragment from TJ-enriched junctional cell fractions. Following sequencing and similarity searching it was cloned and expressed in cells, where it was shown to concentrate at TJs []. Human and mouse isoforms have been identified. Claudin-2 shares ~22-46% overall similarity with other claudin family members at the aminoacid level, displaying highest similarity to claudin-14.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-11 was originally termed oligodendrocyte-specific protein (OSP).It was reclassified as claudin-11 due to its sequence similarity to claudins and its ability to form TJ strands in transfected fibroblasts.Claudin-11 expression is highly regulated during development and it has been postulated that it may play an important role in the growth and differentiation of oligodendrocytes and other cells outside the CNS [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-5 was originally termed lung-specific membrane protein, brainendothelial cell clone 1 protein (BEC1), and transmembrane protein deletedin velo-cardio-facial syndrome (TMVCF). It was reclassified as claudin-5on the basis of cDNA sequence similarity with claudins-1 and -2, and antibody studies that showed it to be expressed at tight junctions []. Claudin-5 may play an important role in development, since the gene is frequently deleted in velo-cardio-facial/DiGeorge syndrome patients [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-8 was identified through searching expressed sequence tag (EST) databases for sequences similar to claudin-1 and -2 []. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have been identified. Claudin-8 shares ~26-58% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-17.Claudin-8 interacts with claudin-4 and recruits it to tight junction in the kidney. In the collecting duct, this interaction is required for the anion-selective paracellular pathway in which chloride reabsorption is coupled with sodium reabsorption [, ].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-6 was identified through searching expressed sequence tag (EST)databases for sequences similar to claudin-1 and -2 []. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have beenidentified. Claudin-6 shares ~25-70% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-9.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-16 was originally termed paracellin-1. It was re-classified as claudin-16 on the basis of its sequence similarity to the claudin family[]. Claudin-16 is involved in renal paracellular Mg2+ resorption and is required for selective paracellular conductance []. Defects in the claudin-16 gene are associated with an autosomal recessive chronic interstitial nephritis with diffuse zonal fibrosis (CINF) [, ].
