PROSITE documentation PDOC01053Short 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:
+----------------------------------------xxxxxxx---------------------------+ | C C C C Extracellular XXXXXXX Cytoplasmic | +-|-|-------|--|-------------------------xxxxxxx---------------------------+ | | | | 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: Last update:December 2004 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Boulay J.-L. Paul W.E. |
| Title | Hematopoietin sub-family classification based on size, gene organization and sequence homology. | |
| Source | Curr. Biol. 3:573-581(1993). | |
| PubMed ID | 15335670 |
| 2 | Authors | Sprang S.R. Bazan J.F. |
| Source | Curr. Opin. Struct. Biol. 3:815-827(1993). |
| 3 | Authors | Leonard W.J. |
| Title | The defective gene in X-linked severe combined immunodeficiency encodes a shared interleukin receptor subunit: implications for cytokine pleiotropy and redundancy. | |
| Source | Curr. Opin. Immunol. 6:631-635(1994). | |
| PubMed ID | 7946053 |
| 4 | Authors | Nicola N.A. Metcalf D. |
| Title | Subunit promiscuity among hemopoietic growth factor receptors. | |
| Source | Cell 67:1-4(1991). | |
| PubMed ID | 1913811 |
| 5 | Authors | Hilton D.J. Zhang J.G. Metcalf D. Alexander W.S. Nicola N.A. Willson T.A. |
| Title | Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 93:497-501(1996). | |
| PubMed ID | 8552669 |
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