PROSITE documentation PDOC00348

SRCR domain signature and profile




Description

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 β-sheet cradling an α-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.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

SRCR_2, PS50287; SRCR domain profile  (MATRIX)

SRCR_1, PS00420; SRCR domain signature  (PATTERN)


References

1AuthorsFreeman M., Ashkenas J., Rees D.J., Kingsley D.M., Copeland N.G., Jenkins N.A., Krieger M.
TitleAn ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.
SourceProc. Natl. Acad. Sci. U.S.A. 87:8810-8814(1990).
PubMed ID1978939

2AuthorsResnick D., Pearson A., Krieger M.
TitleThe SRCR superfamily: a family reminiscent of the Ig superfamily.
SourceTrends Biochem. Sci. 19:5-8(1994).
PubMed ID8140623

3AuthorsHohenester E., Sasaki T., Timpl R.
TitleCrystal structure of a scavenger receptor cysteine-rich domain sheds light on an ancient superfamily.
SourceNat. Struct. Biol. 6:228-232(1999).
PubMed ID10074941
DOI10.1038/6669



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