CR1 curation notes

2026-06-19

• Deep-research attempt with just deep-research-falcon human CR1 --fallback perplexity-lite timed out after 180 seconds with no generated research artifact, so this manual review uses cached UniProt, GOA, Reactome, PANTHER family, and publication evidence.
• CR1/CD35 is a large cell-surface complement receptor whose core functions are C3b/C4b binding, immune-adherence clearance, and complement regulation. UniProt summarizes CR1 as a membrane immune adherence receptor for complement-opsonized pathogens/immune complexes and a complement inhibitor/cofactor.
• C3b/C4b receptor activity is directly supported by deletion-mutagenesis work: recombinant CR1 mediated rosette formation with C3b/C4b-bearing erythrocytes and had factor I cofactor activity PMID:2972794.
• CR1 complement-inhibitory activity is core. The classic receptor-inhibitor paper reports that CR1 promotes dissociation of the alternative pathway C3 convertase, supports C3b/C4b inactivator cleavage, and inactivates classical pathway C3/C5 convertases PMID:6910481.
• C5 convertase decay-accelerating activity is supported by domain mapping; site 1 and a properly spaced site 2 are required for efficient activity PMID:10531307.
• Erythrocyte immune-adherence clearance is a major in vivo role in primates. CR1 on red blood cells binds complement-tagged particles for transport to liver/spleen macrophages, and the paper explicitly names this process immune-adherence clearance PMID:24022490.
• Erythrocyte CR1 cytoskeletal/FAP-1 association and ATP release are real but secondary mechanistic details for immune-adherence transfer, so I kept cytoskeleton, membrane organization, raft, and ATP export annotations non-core PMID:18684861.
• T-cell and B-cell regulatory annotations are real immune-context biology but non-core relative to the general C3b/C4b receptor/cofactor function. T-cell CR1 triggering inhibits proliferation and cytokine protein synthesis PMID:16360013, and CD35/CR1 engagement can support Treg phenotypes PMID:25742728.
• CR1 also acts as a B-cell inhibitory receptor in rheumatoid arthritis contexts, reducing BCR-induced proliferation, plasmablast differentiation, and immunoglobulin production PMID:22962438.
• CR1 interactions with C1q, MBL, and ficolins are biologically meaningful complement-recognition interactions, but generic protein binding is too broad. I marked the corresponding generic annotations as MODIFY to complement binding PMID:23460739.
• CR1 expression in engineered retinal pigment epithelial cells can inhibit C3b/C6 deposition and complement-mediated injury, supporting complement-inhibitory annotations while remaining a therapeutic/model context PMID:31862673.
• High-throughput extracellular exosome annotations and generic FAP-1 protein binding were marked over-annotated because they do not define CR1 core molecular function compared with complement receptor, complement binding, and complement-regulatory terms.

2026-06-20 second-pass audit

The second-pass audit confirmed the existing CR1 review and manual reference metadata. No annotation action changes were needed: CR1 remains curated as a C3b/C4b complement receptor and immune-adherence/complement-regulatory cofactor, with T-cell, B-cell, retinal-therapeutic, cytoskeletal, and generic high-throughput interaction contexts retained as non-core, modified, or over-annotated as already reviewed.