PROSITE documentation PDOC01052

{PDOC01052}
{PS01354; HEMATOPO_REC_L_F3}
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* Long hematopoietin receptor, soluble alpha chains family 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   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
beta chain)  and a short (or no) cytoplasmic domain. They define a structural
subgroup containing the following chains:

 - Interleukin-6 receptor alpha chain (IL6RA).
 - Interleukin-11 receptor alpha chain (IL11RA).
 - Ciliary neurotrophic factor receptor alpha chain (CNTFRA).
 - Interleukin-12 beta chain p40 (IL12BC).
 - Interleukin-12 beta 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  alpha  chains are physiologically active [3]. IL-12
is an  heterodimeric  cytokine  made  of an alpha chain (p35) and a beta chain
(p40). p40  (IL12BC)  can  be  regarded  as  an alpha 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.

-Consensus pattern: [LIV]-x-P-D-P(2)-x(2)-[LIV]-x(8,11)-[LVAM]-x(3)-W-x(2)-P-
                    x-[ST]-W-x(4,6)-[FY]-x-L-x-[FY]-x-[LVI]
-Sequences known to belong to this class detected by the pattern: ALL
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Boulay J.-L.; 





Jean-Louis.Boulay@unibas.ch


-Last update: April 2006 / Pattern 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] Kishimoto T., Taga T., Akira S.
     "Cytokine signal transduction."
     Cell 76:253-262(1994).
     PubMed=8293462
[ 4] Gearing D.P., Cosman D.
     "Homology of the p40 subunit of natural killer cell stimulatory factor
     (NKSF) with the extracellular domain of the interleukin-6 receptor."
     Cell 66:9-10(1991).
     PubMed=2070420

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