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0  structures 45  species 0  interactions 210  sequences 6  architectures

Family: Claudin_3 (PF06653)

Summary: Tight junction protein, Claudin-like

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This is the Wikipedia entry entitled "Claudin". More...

Claudin Edit Wikipedia article

Cellular tight junction-en.svg
Pfam clanCL0375
OPM superfamily194
OPM protein4p79

Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions (zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm.


Claudins are small (20–27 kilodalton (kDa)) transmembrane proteins which are found in many organisms, ranging from nematodes to human beings, and are very similar in their structure, although this conservation is not observed on the genetic level. Claudins span the cellular membrane 4 times, with the N-terminal end and the C-terminal end both located in the cytoplasm, and two extracellular loops which show the highest degree of conservation. The first extracellular loop consists on average of 53 amino acids and the second one, being slightly smaller, of 24 amino acids. The N-terminal end is usually very short (4–10 amino acids), the C-terminal end varies in length from 21 to 63 and is necessary for the localisation of these proteins in the tight junctions.[1] It is suspected that the cysteines of individual or separate claudins form disulfide bonds. All human claudins (with the exception of Claudin 12) have domains that let them bind to PDZ domains of scaffold proteins.


Claudins were first named in 1998 by Japanese researchers Mikio Furuse and Shoichiro Tsukita at Kyoto University.[2] The name claudin comes from Latin word claudere ("to close"), suggesting the barrier role of these proteins.

A recent review discusses evidence regarding the structure and function of claudin family proteins using a systems approach to understand evidence generated by proteomics techniques.[3]


In humans, 24 members of the family have been described.

See also

Additional images


  1. ^ Rüffer C, Gerke V (May 2004). "The C-terminal cytoplasmic tail of claudins 1 and 5 but not its PDZ-binding motif is required for apical localization at epithelial and endothelial tight junctions". Eur. J. Cell Biol. 83 (4): 135–44. doi:10.1078/0171-9335-00366. PMID 15260435.
  2. ^ Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (June 1998). "Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin". J. Cell Biol. 141 (7): 1539–50. doi:10.1083/jcb.141.7.1539. PMC 2132999. PMID 9647647.
  3. ^ Liu F, Koval M, Ranganathan S, Fanayan S, Hancock WS, Lundberg EK, Beavis RC, Lane L, Duek P, McQuade L, Kelleher NL, Baker MS (Dec 2015). "A systems proteomics view of the endogenous human claudin protein family". J Proteome Res. doi:10.1021/acs.jproteome.5b00769. PMC 4777318. PMID 26680015.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Tight junction". More...

Tight junction Edit Wikipedia article

Tight junction
Cellular tight junction-en.svg
Diagram of Tight junction
Latinjunctio occludens
Anatomical terminology

Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens) 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 only in vertebrates. The corresponding junctions that occur in invertebrates are septate junctions.


Tight junctions are composed of a branching network of sealing strands, each strand acting independently from the others. Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. There are at least 40 different proteins composing the tight junctions.[1] These proteins consist of both transmembrane and cytoplasmic proteins. The three major transmembrane proteins are occludin, claudins, and junction adhesion molecule (JAM) proteins. These associate with different peripheral membrane proteins such as ZO-1 located on the intracellular side of plasma membrane, which anchor the strands to the actin component of the cytoskeleton.[2] Thus, tight junctions join together the cytoskeletons of adjacent cells.

Depiction of the transmembrane proteins that make up tight junctions: occludin, claudins, and JAM proteins.

Transmembrane proteins:

  • Occludin was the first integral membrane protein to be identified. It has a molecular weight of ~60kDa. It consists of four transmembrane domains and both the N-terminus and the C-terminus of the protein are intracellular. It forms two extracellular loops and one intracellular loop. These loops help regulate paracellular permeability.[3] Occludin also plays a key role in cellular structure and barrier function.[4]
  • Claudins were discovered after occludin and are a family of 24 different mammalian proteins.[5] They have a molecular weight of ~20kDa. They have a structure similar to that of occludin in that they have four transmembrane domains and similar loop structure. They are understood to be the backbone of tight junctions and play a significant role in the tight junction's ability to seal the paracellular space.[6] Different claudins are found in different locations throughout the human body.
  • Junction Adhesion Molecules (JAM) are part of the immunoglobulin superfamily. They have a molecular weight of ~40kDa. Their structure differs from that of the other integral membrane proteins in that they only have one transmembrane protein instead of four. It helps to regulate the paracellular pathway function of tight junctions and is also involved in helping to maintain cell polarity.[7]


They perform vital functions:[8]

  • They hold cells together.
  • Barrier function, which can be further subdivided into protective barriers and functional barriers serving purposes such as material transport and maintenance of osmotic balance:
    • Tight junctions help to maintain the polarity of cells by preventing the lateral diffusion of integral membrane proteins between the apical and lateral/basal surfaces, allowing the specialized functions of each surface (for example receptor-mediated endocytosis at the apical surface and exocytosis at the basolateral surface) to be preserved. This aims to preserve the transcellular transport.
    • Tight junctions prevent the passage of molecules and ions through the space between plasma membranes of adjacent cells, so materials must actually enter the cells (by diffusion or active transport) in order to pass through the tissue. Investigation using freeze-fracture methods in electron microscopy is ideal for revealing the lateral extent of tight junctions in cell membranes and has been useful in showing how tight junctions are formed.[9] The constrained intracellular pathway exacted by the tight junction barrier system allows precise control over which substances can pass through a particular tissue. (Tight junctions play this role in maintaining the blood–brain barrier.) At the present time, it is still unclear whether the control is active or passive and how these pathways are formed. In one study for paracellular transport across the tight junction in kidney proximal tubule, a dual pathway model is proposed: large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores.[10]

In human physiology there are two main types of epithelia using distinct types of barrier mechanism. Epidermal structures such as skin form a barrier from many layers of keratinized squamous cells. Internal epithelia on the other hand more often rely on tight junctions for their barrier function. This kind of barrier is mostly formed by only one or two layers of cells. It was long unclear whether tight cell junctions also play any role in the barrier function of the skin and similar external epithelia but recent research suggests that this is indeed the case.[11]


Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement:[12]

  • Tight epithelia have tight junctions that prevent most movement between cells. Examples of tight epithelia include the distal convoluted tubule, the collecting duct of the nephron in the kidney, and the bile ducts ramifying through liver tissue. Other examples are the blood-brain barrier and the blood cerebrospinal fluid barrier
  • Leaky epithelia do not have these tight junctions, or have less complex tight junctions. For instance, the tight junction in the kidney proximal tubule, a very leaky epithelium, has only two to three junctional strands, and these strands exhibit infrequent large slit breaks.

See also

TEM of negatively stained proximal convoluted tubule of Rat kidney tissue at a magnification of ~55,000x and 80 kV with Tight junction. Note that the three dark lines of density correspond to the density of the protein complex, and the light lines in between correspond to the paracellular space.


  1. ^ Itallie, Christina M. Van; Anderson, James M. (2009-08-01). "Physiology and Function of the Tight Junction". Cold Spring Harbor Perspectives in Biology. 1 (2): a002584. doi:10.1101/cshperspect.a002584. ISSN 1943-0264. PMC 2742087. PMID 20066090.
  2. ^ Anderson, JM; Van Itallie, CM (August 2009). "Physiology and function of the tight junction". Cold Spring Harb Perspect Biol. 1 (2): a002584. doi:10.1101/cshperspect.a002584. PMC 2742087. PMID 20066090.
  3. ^ Wolburg, Hartwig; Lippoldt, Andrea; Ebnet, Klaus (2006), "Tight Junctions and the Blood-Brain Barrier", Tight Junctions, Springer US, pp. 175–195, doi:10.1007/0-387-36673-3_13, ISBN 9780387332017
  4. ^ Liu, Wei-Ye; Wang, Zhi-Bin; Zhang, Li-Chao; Wei, Xin; Li, Ling (2012-06-12). "Tight Junction in Blood-Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances". CNS Neuroscience & Therapeutics. 18 (8): 609–615. doi:10.1111/j.1755-5949.2012.00340.x. ISSN 1755-5930. PMC 6493516. PMID 22686334.
  5. ^ Schneeberger, Eveline E.; Lynch, Robert D. (June 2004). "The tight junction: a multifunctional complex". American Journal of Physiology. Cell Physiology. 286 (6): C1213–C1228. doi:10.1152/ajpcell.00558.2003. ISSN 0363-6143. PMID 15151915.
  6. ^ Mitic, Laura L.; Van Itallie, Christina M.; Anderson, James M. (August 2000). "Molecular Physiology and Pathophysiology of Tight Junctions I. Tight junction structure and function: lessons from mutant animals and proteins". American Journal of Physiology. Gastrointestinal and Liver Physiology. 279 (2): G250–G254. doi:10.1152/ajpgi.2000.279.2.g250. ISSN 0193-1857.
  7. ^ Luissint, Anny-Claude; Artus, Cédric; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier (2012-11-09). "Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation". Fluids and Barriers of the CNS. 9 (1): 23. doi:10.1186/2045-8118-9-23. ISSN 2045-8118. PMC 3542074. PMID 23140302.
  8. ^ Department, Biology. "Tight Junctions (and other cellular connections)". Davidson College. Retrieved 2015-01-12.
  9. ^ Chalcroft, J. P.; Bullivant, S (1970). "An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture". The Journal of Cell Biology. 47 (1): 49–60. doi:10.1083/jcb.47.1.49. PMC 2108397. PMID 4935338.
  10. ^ Guo, P; Weinstein, AM; Weinbaum, S (Aug 2003). "A dual-pathway ultrastructural model for the tight junction of rat proximal tubule epithelium". American Journal of Physiology. Renal Physiology. 285 (2): F241–57. doi:10.1152/ajprenal.00331.2002. PMID 12670832.
  11. ^ Kirschner, Nina; Brandner, JM (June 2012). "Barriers and more: functions of tight junction proteins in the skin". Annals of the New York Academy of Sciences. 1257: 158–166. doi:10.1111/j.1749-6632.2012.06554.x. PMID 22671602.
  12. ^ Department, Biology. "Tight Junctions and other cellular connections". Davidson College. Retrieved 2013-09-20.

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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Tight junction protein, Claudin-like Provide feedback

This is a family of probable membrane tight junction, Claudin-like, proteins.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR009545

This is a family of probable membrane tight junction, claudin-like, proteins.

Domain organisation

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Pfam Clan

This family is a member of clan Transporter (CL0375), which has the following description:

The members of this superfamily are probably all transporter protein domains. All families normally carry four tansmembrane regions, which in many instances associate into hexameric structures. They are frequently involved in gap-junction formation between cells or in forming pores linking the cytosol with the extracellulare space 1,2]. The clan includes members of the TCDB superfamilies 1.A.24 and 1.A.25.

The clan contains the following 13 members:

Amastin Atthog Claudin_2 Claudin_3 Clc-like Connexin Fig1 GSG-1 Innexin L_HMGIC_fpl Pannexin_like PMP22_Claudin SUR7


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Curation View help on the curation process

Seed source: Pfam-B_21553 (release 10.0)
Previous IDs: DUF1164;
Type: Family
Sequence Ontology: SO:0100021
Author: Moxon SJ , Coggill P
Number in seed: 24
Number in full: 210
Average length of the domain: 162.20 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 89.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.7 28.7
Trusted cut-off 28.7 28.7
Noise cut-off 28.6 28.5
Model length: 165
Family (HMM) version: 13
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trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

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Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;