PROSITE documentation PDOC01051Long hematopoietin receptor, gp130 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 immunoglobin-like domain, an hematopoietin-receptor domain, and 3 fibronectin type-III domains (2 in the leptin receptor). This subgroup was designated as "gp130 family of receptors" [3] and contains the following chains:
- Leptin receptor (LPTR).
- Granulocyte colony stimulating factor receptor (GCSFR).
- Interleukin-6/-11/LIF/OSM/CNTF common β chain (GP130).
- Leukemia inhibiting factor receptor (LIFR).
- Oncostatin-M receptor β chain (OSMR).
- Interleukin-12 receptor β-1 chain (IL12RB1).
- Interleukin-12 receptor β-2 chain (IL12RB2).
A schematic representation of the structure of these receptors is shown below:
+-------+-------------------------+-----------------xxxxxxx-----------------+
|Ig-like| C C C C Extracellular | FnIII (x3) XXXXXXX Cytoplasmic |
+-------+-|-|--|--|---------------+-----------------xxxxxxx-----------------+
| | | | Transmembrane
+-+ +--+
These receptor chains homodimerize (GCSFR, GP130, LPTR) or heterodimerize (GP130 with LIFR or OSMR, IL12RB1 with IL12RB2) upon binding of the cognate cytokine: G-CSF, LIF, OSM, LPT, or the cytokine/α chain complex: IL-6/IL6RA, IL-11/IL11RA, CNTF/CNTFRA, IL-12 (p35/p40) [4,5].
We have used one pattern to detect this family. The motif covers the c-terminal end of the first fibronectin III domain and the n-terminal part of the second fibronectin III domain.
Expert(s) to contact by email: Last update:December 2001 / First entry.
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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 | Mosley B. De Imus C. Friend D. Boiani N. Thoma B. Park L.S. Cosman D. |
| Title | Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. | |
| Source | J. Biol. Chem. 271:32635-32643(1996). | |
| PubMed ID | 8999038 |
| 4 | Authors | Kishimoto T. Taga T. Akira S. |
| Title | Cytokine signal transduction. | |
| Source | Cell 76:253-262(1994). | |
| PubMed ID | 8293462 |
| 5 | Authors | Presky D.H. Yang H. Minetti L.J. Chua A.O. Nabavi N. Wu C.Y. Gately M.K. Gubler U. |
| Title | A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 93:14002-14007(1996). | |
| PubMed ID | 8943050 |
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