PROSITE documentation PDOC00341

Connexins signatures

Gap junctions [1] are specialized regions of the plasma membrane which consist of closely packed pairs of transmembrane channels, the connexons, through which small molecules diffuse from a cell to a neighboring cell. Each connexon is composed of an hexamer of an integral membrane protein which is often referred to as connexin. In a given species there are a number of different, yet structurally related, tissue specific, forms of connexins. The types of connexins which are currently known are listed below.

• Connexin 56 (Cx56).
• Connexin 50 (Cx50) (lens fiber protein MP70).
• Connexin 46 (Cx46) (α-3).
• Connexin 45 (Cx45) (α-6).
• Connexin 43 (Cx43) (α-1).
• Connexin 40 (Cx40) (α-5).
• Connexin 38 (Cx38) (α-2).
• Connexin 37 (Cx37) (α-4).
• Connexin 33 (Cx33) (α-7).
• Connexin 32 (Cx32) (β-1).
• Connexin 31.1 (Cx31.1) (β-4).
• Connexin 31 (Cx31) (β-3).
• Connexin 30.3 (Cx30.3) (β-5).
• Connexin 26 (Cx26) (β-2).

Structurally the connexins consist of a short cytoplasmic N-terminal domain, followed by four transmembrane segments that delimit two extracellular and one cytoplasmic loops; the C-terminal domain is cytoplasmic and its length is variable (from 20 residues in Cx26 to 260 residues in Cx56). The schematic representation of this structure is shown below.

       NH2-***        ***          *************-COOH
             **     **   **      **
             **    **     **    **   Cytoplasmic
          ---**----**-----**----**----------------
             **    **     **    **   Membrane
             **    **     **    **
          ---**----**-----**----**----------------
             **    **     **    **   Extracellular
              **  **       **  **
                **           **

The sequences of the two extracellular loops are well conserved. In both loops there are three conserved cysteines which are involved in disulfide bonds. We have built signature patterns from each of these two loop regions.