PROSITE documentation PDOC00348

{PDOC00348}
{PS00420; SRCR_1}
{PS50287; SRCR_2}
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* SRCR domain signature and profile *
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The scavenger  receptor  cysteine-rich  (SRCR) domain is an ancient and highly
conserved domain  of about 110 residues which is found in diverse secreted and
cell-surface proteins,  like  the  type  I  scavenger  receptor,  the  speract
receptor, CD5/Ly-1,  CD6,  or  complement factor I [1]. Tandem repeats of SRCR
domains are  common in the membrane bound proteins. Most SRCR domains have six
to eight  cysteines  that  participate  in  intradomain disulfide bonds.  SRCR
domains have  been  subdivided  into  two  groups,  A  and B, primarily on the
differences in the spacing pattern between the cysteine residues [2,3].

Although the  biochemical  functions of SRCR domains have not been established
with certainty,  they  are  likely to mediate protein-protein interactions and
ligand binding [2,3].

Determination of the crystal structure of the SRCR domain of M2BP reveals that
the M2NP  SRCR  adopts  a  compact fold of approximate dimensions 22 x 26 x 30
Angstrom, organized around a curved six-stranded beta-sheet cradling an alpha-
helix [3].

Some proteins known to contain one or more SRCR domains are listed below:

 - Mammalian  macrophage  scavenger  receptor  type  I,  a  trimeric  integral
   membrane glycoprotein  implicated in atherosclerosis,   adhesion  and  host
   defense. The  scavenger  receptor  binds a variety of polyanions, including
   chemically modified proteins and lipoproteins, and certain polynucleotides.
 - Mammalian   CD5/Ly-1,  a  protein  expressed  at  the  cell  surface  of  T
   lymphocytes and  a  distinctive  subset of B lymphocytes. It interacts with
   CD72/Lyb-2. There are 3 copies of SRCR in CD5.
 - Mammalian CD6, a lymphocyte cell surface receptor that binds to its ligand,
   activated leukocyte  cell  adhesion  molecule  (ALCAM/CD166),  through  the
   membrane proximal  of  its  three  extracellular  SRCR domains. There are 3
   copies of SRCR in CD6.
 - Mammalian  Mac-2  binding  protein  (M2BP),  a tumor-associated antigen and
   matrix protein.
 - Mammalian  and  amphibian  complement  factor  I  (CFI),  a  protease  that
   regulates the complement cascade.
 - Mammalian macrophage receptor MARCO (2 copies).
 - Vertebrate enteropeptidase (EC 3.4.21.9) (1 copy).
 - Mammalian neurotrypsin (EC 3.4.21.-) (4 copies).
 - Lysyl oxidase like proteins 2 and 3 (4 copies).
 - The sea urchin speract receptor, a transmembrane glycoprotein that mediates
   the activation of sperm by egg peptides.

The signature pattern that we derived spans  part of the N-terminal section of
the domain  and  contain  8 conserved residues. The profile spans the complete
domain.

-Consensus pattern: [GNRVM]-x(5)-[GLKA]-x(2)-[EQ]-x(6)-[WPS]-[GLKH]-x(2)-C-
                    x(3)-[FYW]-x(8)-[CM]-x(3)-G
-Sequences known to belong to this class detected by the pattern: only a small
 minority of all SRCR domains.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: December 2004 / Pattern and text revised.

[ 1] Freeman M., Ashkenas J., Rees D.J., Kingsley D.M., Copeland N.G.,
     Jenkins N.A., Krieger M.
     "An ancient, highly conserved family of cysteine-rich protein domains
     revealed by cloning type I and type II murine macrophage scavenger
     receptors."
     Proc. Natl. Acad. Sci. U.S.A. 87:8810-8814(1990).
     PubMed=1978939
[ 2] Resnick D., Pearson A., Krieger M.
     "The SRCR superfamily: a family reminiscent of the Ig superfamily."
     Trends Biochem. Sci. 19:5-8(1994).
     PubMed=8140623
[ 3] Hohenester E., Sasaki T., Timpl R.
     "Crystal structure of a scavenger receptor cysteine-rich domain sheds
     light on an ancient superfamily."
     Nat. Struct. Biol. 6:228-232(1999).
     PubMed=10074941; DOI=10.1038/6669

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