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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 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.

December 2004 / Pattern and text revised.

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

SRCR_2, PS50287; SRCR domain profile  (MATRIX)

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

• Domain architecture view of Swiss-Prot proteins matching PS50287 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50287 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50287 • Scan Swiss-Prot/TrEMBL entries against PS50287 • view ligand binding statistics

Matching PDB structures: 1BY2 2JA4 2JOP 2JP0 ... [ALL]

SRCR_1, PS00420; SRCR domain signature  (PATTERN)

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.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00420 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00420 • Scan Swiss-Prot/TrEMBL entries against PS00420 • view ligand binding statistics

Matching PDB structures: 1BY2 2OY3 2OYA [ALL]

1	Authors	Freeman M., Ashkenas J., Rees D.J., Kingsley D.M., Copeland N.G., Jenkins N.A., Krieger M.
	Title	An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.
	Source	Proc. Natl. Acad. Sci. U.S.A. 87:8810-8814(1990).
	PubMed ID	1978939

2	Authors	Resnick D., Pearson A., Krieger M.
	Title	The SRCR superfamily: a family reminiscent of the Ig superfamily.
	Source	Trends Biochem. Sci. 19:5-8(1994).
	PubMed ID	8140623

3	Authors	Hohenester E., Sasaki T., Timpl R.
	Title	Crystal structure of a scavenger receptor cysteine-rich domain sheds light on an ancient superfamily.
	Source	Nat. Struct. Biol. 6:228-232(1999).
	PubMed ID	10074941
	DOI	10.1038/6669

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