PROSITE documentation PDOC50923

Sushi/CCP/SCR domain profile

The extracellular sushi domain is characterized by a consensus sequence spanning ~60 residues containing four invariant cysteine residues forming two disulfide-bridges (I-III and II-IV), a highly conserved tryptophan, and conserved glycine, proline, and hydrophobic residues [1]. Sushi domains are known to be involved in many recognition processes, including the binding of several complement factors to fragments C3b and C4b [1]. The sushi domain is also known as the complement controle protein (CCP) module or the short consensus repeat (SCR).

Several structure of the sushi domain have been solved (see for example <PDB:1HCC>) [2]. The sushi domain folds into a small and compact hydrophobic core enveloped by six β-strands and stabilized by two disulfide bridges. The relative structural orientation of the β-2 and β-4 strands is shared by all the sushi structures, whereas the topology of the other strands relative to this central conserved core is variable, especially at the regions that form the interfaces with the preceding and following domains [3].

Some proteins known to contain a sushi domain:

• Mammalian complement receptor type 1 and 2. They mediate cellular binding of particles and immune complexes that have activated complement.
• Mammalian C4b-binding protein α chain. It binds as a cofactor to C3b/C4b inactivator, which then hydrolyzes the complement fragment C4b.
• Mammalian complement factor H-related protein 2. It might be involved in complement regulation.
• Mammalian membrane cofactor protein (MCP), an important membrane protein for protecting host cells from damage by complement. MCP possesses cofactor activity for inactivation of C3b and C4b by serum factor I.
• Mammalian complement decay-accelerating factor (DAF). This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and C3 activation. Interaction of DAF with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade.
• Mammalian β-2-glycoprotein I or apolipoprotein H. It binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. It may prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.
• Mammalian P-selectin, a Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. It mediates the interaction of activated endothelial cells or platelets with leukocytes.
• Mammalian neurocan core protein. It may modulate neuronal adhesion and neurite growth during development by binding to neural cell adhesion molecules (NG-CAM and N-CAM).
• Mammalian complement C2. It is part of the classical pathway of the complement system. It is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase.
• Mammalian mannan-binding lectin serine protease 2. A trypsin protease that presumably plays an important role in the initiation of the mannose-binding lectin (MBL) complement activation pathway. After activation it cleaves C4 generating C4a and C4b.
• Mammalian thyroid peroxidase, a key enzyme in the process of thyroid hormone synthesis.
• Mammalian γ-aminobutyric acid type B receptor, subunit 1 (GABA-B receptor 1).
• Mammalian haptoglobin. It combines with free plasma hemoglobin, preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin, while making the hemoglobin accessible to degradative enzymes.
• Drosophila locomotion-related protein Hikaru genki.
• Viral complement control protein. It serves to protect the virus against complement attack by inhibiting both classical and alternative pathways of complement activation. It binds C3b and C4b.

The profile we developed covers the whole sushi domain.