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0  structures 153  species 0  interactions 1124  sequences 13  architectures

Family: Claudin_2 (PF13903)

Summary: PMP-22/EMP/MP20/Claudin tight junction

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

Claudin Edit Wikipedia article

For the Arthurian character, see Prince Claudin. For the French composer, see Claudin de Sermisy.
Cellular tight junction-en.svg
Symbol PMP22_Claudin
Pfam PF00822
Pfam clan CL0375
InterPro IPR004031
TCDB 1.H.1
OPM superfamily 492
OPM protein 4p79

Claudins are a family of proteins that are the most important components of the tight junctions, where they 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.


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. 

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
Latin junctio occludens
TH H1.
FMA 67397
Anatomical terminology

Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens), are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex 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. Although more proteins are present, the major types are the claudins and the occludins. 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. Thus, tight junctions join together the cytoskeletons of adjacent cells.


They perform vital functions:[1]

  • 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.[2] 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.[3]

In human physiology there are two main types of epithelia using distinct types of barrier mechanism. Dermal structures such as skin form a barrier from many layers of keratinised 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.[4]


Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement:[5]

  • 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.
  • 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. ^ Department, Biology. Davidson College Retrieved 2013-09-20.  Missing or empty |title= (help)
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ Department, Biology. "Tight Junctions and other cellular connections". Davidson College. Retrieved 2013-09-20. 

External links

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.

PMP-22/EMP/MP20/Claudin tight junction Provide feedback

Members of this family are claudins, that form tight junctions between cells.

Literature references

  1. Hewitt KJ, Agarwal R, Morin PJ;, BMC Cancer. 2006;6:186.: The claudin gene family: expression in normal and neoplastic tissues. PUBMED:16836752 EPMC:16836752

  2. Kominsky SL;, Expert Rev Mol Med. 2006;8:1-11.: Claudins: emerging targets for cancer therapy. PUBMED:16887048 EPMC:16887048

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004031

Several vertebrate small integral membrane glycoproteins are evolutionary related [PUBMED:7499407, PUBMED:7499420, PUBMED:8996089], including eye lens specific membrane protein 20 (MP20 or MP19); epithelial membrane protein-1 (EMP-1), which is also known as tumor-associated membrane protein (TMP) or as squamous cell-specific protein Cl-20; epithelial membrane protein-2 (EMP-2), which is also known as XMP; epithelial membrane protein-3 (EMP-3), also known as YMP; and peripheral myelin protein 22 (PMP-22), which is expressed in many tissues but mainly by Schwann cells as a component of myelin of the peripheral nervous system (PNS). PMP-22 probably plays a role both in myelinization and in cell proliferation. Mutations affecting PMP-22 are associated with hereditary motor and sensory neuropathies such as Charcot-Marie-Tooth disease type 1A (CMT-1A) in human or the trembler phenotype in mice. The proteins of this family are about 160 to 173 amino acid residues in size, and contain four transmembrane segments. PMP-22, EMP-1, -2 and -3 are highly similar, while MP20 is more distantly related. This family also includes the claudins, which are components of tight junctions. Some members of the Clarin family are also included in this entry. Some members of the TMEM47, TMEM178 and TMEM182 family are included in this entry.

Gene Ontology

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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 12 members:

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


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Seed source: Jackhmmer:A6NFC5
Previous IDs: none
Type: Family
Author: Coggill P
Number in seed: 14
Number in full: 1124
Average length of the domain: 177.10 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 71.20 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.1 29.1
Trusted cut-off 29.1 29.1
Noise cut-off 29.0 29.0
Model length: 193
Family (HMM) version: 2
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