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{PDOC01053}
{PS01355; HEMATOPO_REC_S_F1}
{BEGIN}
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* Short hematopoietin receptor family 1 signature *
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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}