Claudin
Encyclopedia
Claudins are a family of protein
s that are the most important components of the tight junction
s, 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.
(kDa)) transmembrane protein
s which are found in many organisms, ranging from nematode
s 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 acid
s 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. It is suspected that the cysteine
s 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 domain
s of scaffold protein
s.
. The name claudin comes from Latin
word claudere ("to close"), suggesting the barrier role of these proteins.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that are the most important components of the tight junction
Tight junction
Tight junctions, or 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...
s, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm.
Structure
Claudins are small (20–27 kilodaltonAtomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
(kDa)) transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s which are found in many organisms, ranging from nematode
Nematode
The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...
s to human
Human
Humans are the only living species in the Homo genus...
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
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...
and the C-terminal end
C-terminal end
The C-terminus is the end of an amino acid chain , terminated by a free carboxyl group . When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus...
both located in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
, and two extracellular loops which show the highest degree of conservation. The first extracellular loop consists on average of 53 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s 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. It is suspected that the cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s of individual or separate claudins form disulfide bonds. All human claudins
Bill Gates
William Henry "Bill" Gates III is an American business magnate, investor, philanthropist, and author. Gates is the former CEO and current chairman of Microsoft, the software company he founded with Paul Allen...
(with the exception of Claudin 12) have domains that let them bind to PDZ domain
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
s of scaffold protein
Scaffold protein
In biology, scaffold proteins are crucial regulators of many key signaling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes...
s.
History
Claudins were first named in 1998 by the Japanese researchers Mikio Furuse and Shoichiro Tsukita at the Kyoto UniversityKyoto University
, or is a national university located in Kyoto, Japan. It is the second oldest Japanese university, and formerly one of Japan's Imperial Universities.- History :...
. The name claudin comes from Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
word claudere ("to close"), suggesting the barrier role of these proteins.
Genes
In humans, 24 members of the family have been described.- CLDN1CLDN1Claudin-1 is a protein that in humans is encoded by the CLDN1 gene. It belongs to the group of claudins.-Interactions:CLDN1 has been shown to interact with CLDN5 and CLDN3.-Further reading:...
, CLDN2CLDN2Claudin-2 is a protein that in humans is encoded by the CLDN2 gene. It belongs to the group of claudins. -Function:Claudin-2 is expressed in cation-leaky epithelia such as that of the kidney proximal tubule. Mice that are deficient in claudin-2 have reduced reabsorption of Na+ in the proximal...
, CLDN3CLDN3Claudin 3, also known as CLDN3, is a protein which in humans is encoded by the CLDN3 gene. It is a member of the claudin protein family....
, CLDN4CLDN4Claudin 4, also known as CLDN4, is a protein which in humans is encoded by the CLDN4 gene. It belongs to the group of claudins.This gene encodes an integral membrane protein, which belongs to the claudin family. The protein is a component of tight junction strands and may play a role in internal...
, CLDN5CLDN5Claudin-5 is a protein that in humans is encoded by the CLDN5 gene. It belongs to the group of claudins.-Interactions:CLDN5 has been shown to interact with CLDN1 and CLDN3.-Further reading:...
, CLDN6CLDN6Claudin-6 is a protein that in humans is encoded by the CLDN6 gene. It belongs to the group of claudins.-Further reading:...
, CLDN7CLDN7Claudin-7 is a protein that in humans is encoded by the CLDN7 gene. It belongs to the group of claudins.-Further reading:...
, CLDN8CLDN8Claudin-8 is a protein that in humans is encoded by the CLDN8 gene. It belongs to the group of claudins.-Further reading:...
, CLDN9CLDN9Claudin-9 is a protein that in humans is encoded by the CLDN9 gene. It belongs to the group of claudins.This gene is involved in hearing.-Further reading:...
, CLDN10CLDN10Claudin-10 is a protein that in humans is encoded by the CLDN10 gene. It belongs to the group of claudins.-Further reading:...
, CLDN11CLDN11Claudin-11 is a protein that in humans is encoded by the CLDN11 gene. It belongs to the group of claudins.-Further reading:...
, CLDN12CLDN12Claudin-12 is a protein that in humans is encoded by the CLDN12 gene. It belongs to the group of claudins.-Further reading:...
, CLDN13, CLDN14CLDN14Claudin-14 is a protein that in humans is encoded by the CLDN14 gene. It belongs to the group of claudins.-Further reading:...
, CLDN15CLDN15Claudin-15 is a protein that in humans is encoded by the CLDN15 gene. It belongs to the group of claudins.-Further reading:...
, CLDN16CLDN16Claudin-16 is a protein that in humans is encoded by the CLDN16 gene. It belongs to the group of claudins.-Further reading:...
, CLDN17CLDN17Claudin-17 is a protein that in humans is encoded by the CLDN17 gene. It belongs to the group of claudins.-Further reading:...
, CLDN18CLDN18Claudin-18 is a protein that in humans is encoded by the CLDN18 gene. It belongs to the group of claudins.-Further reading:...
, CLDN19CLDN19Claudin-19 is a protein that in humans is encoded by the CLDN19 gene. It belongs to the group of claudins. Claudin-19 has been implicated in magnesium transport.-Further reading:...
, CLDN20CLDN20Claudin-20 is a protein that in humans is encoded by the CLDN20 gene. It belongs to the group of claudins.-Further reading:...
, CLDN21, CLDN22CLDN22Claudin-22 is a protein that in humans is encoded by the CLDN22 gene. It belongs to the group of claudins.-Further reading:...
, CLDN23