{PDOC01053} {PS01355; HEMATOPO_REC_S_F1} {BEGIN} *************************************************** * 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 beta chain receptors KH97/AIC2B and AIC2A). They define a structural subgroup containing the following chains: - Interleukin-2 receptor beta chain (IL2RB) - Interleukin-2 receptor common gamma chain (IL2RG) - Interleukin-3 receptor beta chain (AIC2A) - Interleukin-3/-5/GM-CSF receptor common beta chain (KH97/AIC2B) - Interleukin-4 receptor alpha chain (IL4RA) - Interleukin-7 receptor alpha chain (IL7RA) - Interleukin-9 receptor alpha 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 alpha 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 beta 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. -Consensus pattern: [LIVF]-x(9)-[LIV]-[RK]-x(9,20)-W-S-x-W-S-x(4)-[FYW] -Sequences known to belong to this class detected by the pattern: ALL -Other sequence(s) detected in Swiss-Prot: the leptin receptors. -Expert(s) to contact by email: Boulay J.-L.; Jean-Louis.Boulay@unibas.ch -Last update: December 2004 / Pattern and text revised. [ 1] Boulay J.-L., Paul W.E. "Hematopoietin sub-family classification based on size, gene organization and sequence homology." Curr. Biol. 3:573-581(1993). PubMed=15335670 [ 2] Sprang S.R., Bazan J.F. Curr. Opin. Struct. Biol. 3:815-827(1993). [ 3] Leonard W.J. "The defective gene in X-linked severe combined immunodeficiency encodes a shared interleukin receptor subunit: implications for cytokine pleiotropy and redundancy." Curr. Opin. Immunol. 6:631-635(1994). PubMed=7946053 [ 4] Nicola N.A., Metcalf D. "Subunit promiscuity among hemopoietic growth factor receptors." Cell 67:1-4(1991). PubMed=1913811 [ 5] Hilton D.J., Zhang J.G., Metcalf D., Alexander W.S., Nicola N.A., Willson T.A. "Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor." Proc. Natl. Acad. Sci. U.S.A. 93:497-501(1996). PubMed=8552669 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}