PROSITE documentation PDOC01053
Short hematopoietin receptor family 1 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 are structurally related such that their extracellular parts strictly contain the 200 amino-acids hematopoietin domain (duplicated in IL-3/-5/GM-CSF β chain receptors KH97/AIC2B and AIC2A). They define a structural subgroup containing the following chains:

  • Interleukin-2 receptor β chain (IL2RB)
  • Interleukin-2 receptor common γ chain (IL2RG)
  • Interleukin-3 receptor β chain (AIC2A)
  • Interleukin-3/-5/GM-CSF receptor common β chain (KH97/AIC2B)
  • Interleukin-4 receptor α chain (IL4RA)
  • Interleukin-7 receptor α chain (IL7RA)
  • Interleukin-9 receptor α chain (IL9RA)

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

 | C C       C  C  Extracellular          XXXXXXX   Cytoplasmic             |
   | |       |  |                      Transmembrane
   +-+       +--+

IL4RA, IL7RA and IL9RA are specific α chain receptors for IL-4, IL-7 and IL-9 respectively, whereas IL2RB is common to IL-2 and IL-15 (IL2RA and IL15RA are not members of the hematopoietin receptor superfamily). IL2RG is part of IL-2, IL-15, IL-7, IL-9 and IL-4 form I receptor complexes [3]. KH97/AIC2B chain is part of GM-CSF, IL-3 and IL-5 receptor complexes and in the mouse, AIC2B can be substituted by AIC2A, an IL-3 specific β chain receptor [4]. Together with either IL13RA1 or IL13RA2, IL4RA is also part of the IL-13 receptor complex for which IL-4 can compete with IL-13 (IL-4 receptor complex form II) [5].

We have used one pattern to detect this subfamily. The motif is located at the carboxy-terminal part of the 200 amino acid hematopoietin domain.

Expert(s) to contact by email:

Boulay J.-L.

Last update:

December 2004 / Pattern and text revised.


Technical section

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

HEMATOPO_REC_S_F1, PS01355; Short hematopoietin receptor family 1 signature  (PATTERN)


1AuthorsBoulay J.-L. Paul W.E.
TitleHematopoietin sub-family classification based on size, gene organization and sequence homology.
SourceCurr. Biol. 3:573-581(1993).
PubMed ID15335670

2AuthorsSprang S.R. Bazan J.F.
SourceCurr. Opin. Struct. Biol. 3:815-827(1993).

3AuthorsLeonard W.J.
TitleThe defective gene in X-linked severe combined immunodeficiency encodes a shared interleukin receptor subunit: implications for cytokine pleiotropy and redundancy.
SourceCurr. Opin. Immunol. 6:631-635(1994).
PubMed ID7946053

4AuthorsNicola N.A. Metcalf D.
TitleSubunit promiscuity among hemopoietic growth factor receptors.
SourceCell 67:1-4(1991).
PubMed ID1913811

5AuthorsHilton D.J. Zhang J.G. Metcalf D. Alexander W.S. Nicola N.A. Willson T.A.
TitleCloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor.
SourceProc. Natl. Acad. Sci. U.S.A. 93:497-501(1996).
PubMed ID8552669

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