PROSITE documentation PDOC00205
Cadherin domain signature and profile


Cadherins [1,2] are a family of animal glycoproteins responsible for calcium-dependent cell-cell adhesion. Cadherins preferentially interact with themselves in a homophilic manner in connecting cells; thus acting as both receptor and ligand. A wide number of tissue-specific forms of cadherins are known, for example:

  • Epithelial (E-cadherin) (CDH1).
  • Neural (N-cadherin) (CDH2).
  • Placental (P-cadherin) (CDH3).
  • Retinal (R-cadherin) (CDH4).
  • Vascular endothelial (VE-cadherin) (CDH5).
  • Kidney (K-cadherin) (CDH6).
  • Cadherin-8 (CDH8).
  • Cadherin-9 (CDH9).
  • Osteoblast (OB-cadherin) (CDH11).
  • Brain (BR-cadherin) (CDH12).
  • T-cadherin (truncated cadherin) (CDH13).
  • Muscle (M-cadherin) (CDH15).
  • Kidney (Ksp-cadherin) (CDH16).
  • Liver-intestine (LI-cadherin) (CDH17).

Structurally, cadherins are built of the following domains: a signal sequence, followed by a propeptide of about 130 residues, then an extracellular domain of around 600 residues, then a transmembrane region, and finally a C-terminal cytoplasmic domain of about 150 residues. The extracellular domain can be sub-divided into five parts: there are four repeats of about 110 residues followed by a region that contains four conserved cysteines. It is suggested that the calcium-binding region of cadherins is located in the extracellular repeats.

Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins:

  • Desmoglein 1 (desmosomal glycoprotein I).
  • Desmoglein 2.
  • Desmoglein 3 (Pemphigus vulgaris antigen).

Other proteins that include cadherin domains are:

  • Drosophila fat protein [3], a huge protein of over 5000 amino acids that contains 34 cadherin-like repeats in its extracellular domain. Homologs of fat are found in mammals.
  • Protocadherins (6 copies).
  • Proto-oncogene tyrosine-protein kinase receptor ret (1 copy).

The signature pattern we have developed for the repeated domain is located in it the C-terminal extremity which is its best conserved region. The pattern includes two conserved aspartic acid residues as well as two asparagines; these residues could be implicated in the binding of calcium. We have also developed a profile that spans the complete domain.


This pattern is found in the first, second, and fourth copies of the repeated domain. In the third copy there is a deletion of one residue after the second conserved Asp.

Last update:

May 2004 / Text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

CADHERIN_2, PS50268; Cadherins domain profile  (MATRIX)

CADHERIN_1, PS00232; Cadherin domain signature  (PATTERN)


1AuthorsTakeichi M.
TitleCadherins: a molecular family important in selective cell-cell adhesion.
SourceAnnu. Rev. Biochem. 59:237-252(1990).
PubMed ID2197976

2AuthorsTakeichi M.
SourceTrends Genet. 3:213-217(1987).

3AuthorsMahoney P.A. Weber U. Onofrechuk P. Biessmann H. Bryant P.J. Goodman C.S.
TitleThe fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily.
SourceCell 67:853-868(1991).
PubMed ID1959133

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