PROSITE documentation PDOC01054 [for PROSITE entry PS01356]

Short hematopoietin receptor family 2 signature

A number of receptors for lymphokines, hematopoietic growth factors and growth hormone-related molecules have been found to share a common binding domain. These receptors are designated as hematopoietin receptors [1,2] and the corresponding ligands as hematopoietins. Further, hematopoietins have been subdivided into two major structural groups: Large/long and small/short hematopoietins.

One subset of individual receptor chains that are part of receptor complexes for small hematopoietins contain common structural elements in their extracellular parts: an immunoglobulin-like domain at the N-terminal end of the hematopoietin receptor domain and a rather short cytoplasmic domain. They define a structural subgroup containing the following chains:

• Granulocyte/macrophage colony stimulating factor receptor α (GMCSFRA).
• Interleukin-3 receptor α chain (IL3RA).
• Interleukin-5 receptor α chain (IL5RA).
• Interleukin-13 receptor α-1 chain (IL13RA1).
• Interleukin-13 receptor α-2 chain (IL13RA2).

A schematic representation of the structure of these receptors is shown below:

 +-----------+-------------------------------------------xxxxxxx-------------+
 |  Ig-like  |  C C     C  C         Extracellular       XXXXXXX Cytoplasmic |
 +-----------+--|-|-----|--|-----------------------------xxxxxxx-------------+
                | |     |  |                          Transmembrane
                +-+     +--+

GMCSFRA, IL3RA or IL5RA chains of this subgroup bind to their cognate cytokines: GM-CSF, IL-3 and IL-5, with a common β chain, KH97/AIC2B [3].

Either IL13RA1 chain or IL13RA2 chain form the IL13R complex together with IL4RA chain. IL-4 can compete with IL-13 to bind to either IL13R form [4].

We have used one pattern to detect this subfamily. The motif is located a the N-terminal end of the 200 amino acid hematopoietin domain.