CR1L

Model summary

A human cell-surface regulator that presents a long extracellular array of complement-control modules to bind multiple partners and assemble receptor complexes that tune complement pathway activity. By organizing high-avidity assemblies at the membrane, it modulates complement activation and restrains downstream cell lysis, acting as a checkpoint that limits complement-dependent cytotoxicity while coordinating with adhesion machinery.

Predicted Gene Ontology terms

1. 01

   I begin by examining the InterPro architecture, which is dominated by tandem Sushi/SCR/CCP modules that span nearly the entire ectodomain.

   The N-terminal CCP core is explicitly annotated by IPR000436 (Sushi/SCR/CCP domain) at residues 33–93, followed by additional CCP repeats annotated separately at 94–155, 156–226, 228–285, 287–347, 348–410, 411–472, and 354–542. These repeats are further grouped by superfamily signatures IPR035976 (Sushi/SCR/CCP superfamily) at 35–224, 231–294, 289–351, and 354–542, reinforcing a multi-CCP extracellular array. The family-level assignment IPR050350 (Complement & Cell Adhesion Regulators, residues 32–301) ties these CCP arrays to complement control and adhesion pathways. The ordered series of CCP domains creates a rigid yet modular scaffold that binds complement components and cell-surface partners with high avidity and specificity. This CCP architecture is characteristic of soluble and membrane-associated complement regulators and adhesion molecules that operate through multivalent protein binding rather than catalysis.

2. 02

   From this CCP-based scaffold, the molecular function resolves as protein binding (GO:0005515).

   CCP modules mediate high-affinity interactions with complement factors (e.g., C3b/C4b) and with cell-surface receptors; the repeated CCP units cause avid, cooperative binding that stabilizes multiprotein assemblies rather than performing enzymatic chemistry.

3. 03

   These binding activities drive two connected biological processes.

   First, the CCP array is a hallmark of regulators that tune the alternative pathway of complement activation; thus it directly supports regulation of complement activation (GO:0030449). By stabilizing or redirecting complement assemblies, the protein modulates convertase formation and decay. Second, by constraining complement amplification and membrane attack complex deposition, it causally reduces downstream cell lysis, aligning with regulation of complement-dependent cytotoxicity (GO:1903659). Together, these processes position the protein as a checkpoint that tempers complement-driven effector functions.

4. 04

   The cellular context follows from the CCP-rich ectodomain and the absence of intracellular catalytic motifs.

   CCP arrays are classically displayed on type I single-pass membrane proteins or secreted glycoproteins that assemble into receptor complexes at the cell surface. The annotation of a single-pass membrane topology and the CCP-mediated assembly of surface complexes supports localization to a receptor complex (GO:0043235). The extracellular CCP array projects into the pericellular space, while a short cytosolic tail anchors the protein in the membrane; this arrangement enables avid extracellular binding and intracellular complex formation.

5. 05

   Mechanistically, the tandem CCP modules create a polyvalent extracellular platform that captures complement components and co-receptors to modulate pathway flux.

   I hypothesize that the protein assembles with cell-surface receptor complexes—likely integrins and/or other adhesion receptors—to spatially restrict complement deposition. By docking complement factors and adhesion partners, it biases the assembly/disassembly of C3/C5 convertases and limits membrane attack complex formation. Candidate interaction partners include complement components (C3b, C4b), the assembly factor properdin, and cell-surface adhesion receptors that form higher-order complexes; these associations collectively enforce complement regulation and cytotoxicity control at membrane microdomains.