Accession number: PF00028
Cadherin domain
Conserved motifs:
DRE, DXNDNAPXF, and DXD
Description
Cadherins are a family of adhesion molecules that mediate Ca2+-dependent cell-cell adhesion in
all solid tissues of the organism which modulate a wide variety of processes including cell
polarisation and migration [MEDLINE:2197976], [MEDLINE:],[MEDLINE:14570569]. Cadherin-mediated
cell-cell junctions are formed as a result of interaction between extracellular domains of
identical cadherins, which are located on the membranes of the neighbouring cells. The stability
of these adhesive junctions is ensured by binding of the intracellular cadherin domain with the
actin cytoskeleton. There are a number of different isoforms distributed in a tissue-specific
manner in a wide variety of organisms. Cells containing different cadherins tend to segregate
in vitro, while those that contain the same cadherins tend to preferentially aggregate together.
This observation is linked to the finding that cadherin expression causes morphological changes
involving the positional segregation of cells into layers, suggesting they may play an important
role in the sorting of different cell types during morphogenesis, histogenesis and regeneration.
They may also be involved in the regulation of tight and gap junctions, and in the control of
intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component
of intercellular desmosome junctions involved in the interaction of plaque proteins.
Structurally, cadherins comprise a number of domains: classically, these include a signal sequence;
a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated
extracellular cadherin domains, 4 of which are cadherin repeats, and the fifth contains 4 conserved
cysteines and a N-terminal cytoplasmic domain [MEDLINE:11736639]. However, proteins are designated
as members of the broadly defined cadherin family if they have one or more cadherin repeats.
A cadherin repeat is an independently folding sequence of approximately 110 amino acids that
contains motifs with the conserved sequences DRE, DXNDNAPXF, and DXD. Crystal structures have
revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved
Ca2+-binding pocket at the domain-domain interface. Cadherins depend on calcium for their function:
calcium ions bind to specific residues in each cadherin repeat to ensure its proper folding, to
confer rigidity upon the extracellular domain and is essential for cadherin adhesive function and
for protection against protease digestion .
Description text from InterPro entry IPR002126
From Cadherin Superfamily Genes webpage at:
http://www.mrc-lmb.cam.ac.uk/genomes/Cadherins/cad_web_pages.html
Cadherins are Calcium dependant cell adhesion molecules. They play an important role in embryonic
morphogenesis and the formation of solid tissues.
Classical cadherins consist of 5 tandemly repeated extracellular cadherin domains, a transmembrane
region and a cytoplasmic region, (eg. CAD1_CHICK). Protocadherins also exist, they have many more
tandemly repeated cadherin domains, (eg. FAT_DROME).
Cadherins are normally anchored via their cytoplasmic region through catenins to cytoskeletal actin
microfilaments.
Two cadherins within one cell dimerise through homophilic contacts on domain 1. A dimer can then
adhere, (forming anti-parallel contacts creating a zipper formation) to two other dimers on
neighbouring cells.
Reference:
The cadherin superfamily of proteins in Caenorhabditis elegans and Drosophila melanogaster.
Emma Hill, Ian Broadbent, Cyrus Chothia & Jonathan Pettitt. JMB. (2001), 305, (5), 1011-1024.
From The Cadherin Resource at:
http://calcium.uhnres.utoronto.ca/cadherin/pub_pages/general/index.htm
Classical cadherins have a well conserved cytoplasmic domains. Chordate classic cadherins have an
extracellular domain organization composed of five cadherin repeats. Chordate classical cadherins can
be further sub-divided into type I and type II. Type I cadherins have a His-Arg-Val sequence in the
N-terminal cadherin repeat. Type II cadherins are all chordate classical cadherins not in type I.
Nonchordate classic cadherins have an extracellular domain organization composed of at least two
cadherin repeats. In contrast to chordates, nonchordate classic cadherins have a variable number of
repeats in the extracellular domain (e.g. HMR-1 in C. elegans has 2 repeats, and DN-cadherin in
Drosophila has 15 repeats). Also, they have additional domains that are inserted between the cadherin
repeats and the transmembrane domain. These domains include one or two Laminin A G domains, several
cysteine-rich repeats with similarity to the epidermal growth factor (EGF).
Desmosomal cadherins are expressed in desmosomes and are essential for desmosome formation. They
contain 5 extracellular cadherin repeats like chordate classical cadherins. Tyrosine receptor kinase
(RET) cadherins have a tyrosine kinase domain in its cytoplasmic domain. The extracellular domain
contains one cadherin repeat.
Fat-like cadherins have a very large extracellular domains with many cadherin repeats (19 in CDH-3, 27
in Dachsous, 34 in Fat, hFat, and rFAT). As well, Fat, hFat, rFAT and CDH-3 contain epidermal growth
factor (EGF)-like and Laminin AG-domain-like regions. These regions are localized between the cadherin
and transmembrane domains. Fat-like cadherins may function in adhesion or signaling, or both.
Flamingo cadherins contain a seven-pass transmembrane receptor which shows some similarity to the
secretin family of G-protein linked receptors. The large extracellular domain of Flamingo contains
nine cadherin repeats, two globular laminin motifs, and four cystein-rich EGF motifs. Also present is
a subdomain located between the last cadherin repeat and the first EGF domain which is highly
conserved across species. This region is known as the Flamingo box.
