PROSITE documentation PDOC01052Long hematopoietin receptor, soluble alpha chains family 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 large hematopoietins contain common structural elements in their extracellular parts: an immunoglobulin-like domain at the N-terminal end of the hematopoietin receptor domain (except for the EBCV-induced interleukin-12 β chain) and a short (or no) cytoplasmic domain. They define a structural subgroup containing the following chains:
- Interleukin-6 receptor α chain (IL6RA).
- Interleukin-11 receptor α chain (IL11RA).
- Ciliary neurotrophic factor receptor α chain (CNTFRA).
- Interleukin-12 β chain p40 (IL12BC).
- Interleukin-12 β chain induced by Epstein-Barr Virus (EBI3).
A schematic representation of the structure of these receptors is shown below:
+-----------+--------------------------------------------+
| Ig-like | C C C C Extracellular |
+-----------+--|-|-----|--|------------------------------+
| | | |
+-+ +--+
Members of this subgroup bind to their cognate cytokines with low affinity and possess transmembrane and short cytoplasmic domains (IL6RA and IL11RA), or are GPi-linked membrane proteins (CNTFRA). Truncated soluble forms of IL-6 and CNTF receptors α chains are physiologically active [3]. IL-12 is an heterodimeric cytokine made of an α chain (p35) and a β chain (p40). p40 (IL12BC) can be regarded as an α chain receptor devoid of cytoplasmic domain [4]. Members of this family have the ability to bind corresponding cytokines with no signalling function.
We have used one pattern to detect this family. The motif is located in the middle of the 200 amino acids hematopoietin domain.
Expert(s) to contact by email: Last update:April 2006 / Pattern 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 | Kishimoto T. Taga T. Akira S. |
| Title | Cytokine signal transduction. | |
| Source | Cell 76:253-262(1994). | |
| PubMed ID | 8293462 |
| 4 | Authors | Gearing D.P. Cosman D. |
| Title | Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor. | |
| Source | Cell 66:9-10(1991). | |
| PubMed ID | 2070420 |
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