Human CR2 (CD21), HGNC:2336, UniProt P20023 is a complement-fragment receptor with extracellular complement-control repeats, one membrane anchor and a short cytoplasmic tail. The central function is recognition of C3-derived ligands in a B-cell co-receptor system that amplifies activation. The review retains one complement-receptor/B-cell activation core. EBV entry, CD23 binding, interferon-associated responses and the reported DNA interaction are positive contexts with their own experimental limits.
The source evidence file contains the complete 39 current source objects and literal GOA records, product reconstruction, exact rule predicates, actual PAINT path/IBDs, donor records, pathway component paths and public primary-source locators. No historical review was present, so no annotation has been retired or merged away. Original source fields and ordinary qualifiers are unchanged. The assessment adds no NEW annotation.
The C3d mutagenesis study actually assayed “mutant iC3b molecules”, so its complement-binding assertion spans a C3d-region interface in a larger complement product. This supports retaining GO:0001848 for that source. The two CR2–C3d structural assertions can be refined to the specific C3d-binding child GO:0001854. (PMID:11034390(https://pubmed.ncbi.nlm.nih.gov/11034390/); 1GHQ; 3OED.)
The primary deposits authenticate human CR2 canonical residues 21–153, with an A prefix in 1GHQ and an MG prefix in 3OED. They are isolated N-terminal domain complexes, not intact receptor or four-product comparisons. The later study disputes the earlier interface geometry, including crystallization conditions, without disputing C3d recognition. Both Science full articles remained unavailable after bounded retrieval attempts; the complete abstracts and authentic deposits provide the actual accessible evidence. (PMID:11387479(https://pubmed.ncbi.nlm.nih.gov/11387479/); PMID:21527715(https://pubmed.ncbi.nlm.nih.gov/21527715/).)
The receptor-complex literature describes CR2 as a “ligand-binding subunit” associated with CD19. Reciprocal immunoprecipitation and K562 reconstitution distinguish the CR2/CD19 association from proteins primarily associated with CD19. The later CD19/CD21/TAPA-1/Leu-13 work provides additional surface-complex and signaling evidence. These papers' complete abstracts were read, but their full Methods were not recovered; the experimental curator assertions are retained at the stated resolution. (PMID:1702139(https://pubmed.ncbi.nlm.nih.gov/1702139/); PMID:1383329(https://pubmed.ncbi.nlm.nih.gov/1383329/).)
The human CD21/FCRL5 study reports physical association and stronger calcium responses following joint CD21/FCRL5/BCR engagement, including tonsil B cells. Its conclusion that these cells could “robustly respond” to C3-fragment-loaded immune complexes supports B-cell activation without making CR2 a kinase. This is also why the broad immune-response NAS assertion is refined to B-cell activation. (PMID:30107486(https://pubmed.ncbi.nlm.nih.gov/30107486/).)
GO:0004875 is retained in the compact core because C3d, C3dg and iC3b are genuine ligand contexts of the shared receptor activity. It does not imply C3a or C5a recognition. The broad existing signaling-receptor-complex class GO:0043235 fits the independently established assembly. Its plasma-membrane child GO:0098802 explicitly discourages direct annotation, and GO:0019815 defines the antigen-binding immunoglobulin/Ig-alpha/Ig-beta BCR, not automatically the CD21/CD19/CD81 co-receptor complex. A finer complex identifier is therefore not invented.
The original 1992 article was recovered as its three-page publisher PDF. Human CD21 cDNA expressed in BHK-21 cells binds CD23 liposomes, with mock-transfected cells, control liposomes and antibody competition. Its functional experiment is captioned “Engagement of CD21”: soluble CD23 fusion protein or anti-CD21 is combined with IL-4, and IgE output is measured. This is not an independently demonstrated CR2-triggered change in CD23 receptor activity. Refining the existing receptor-ligand assertion to immunoglobulin-receptor binding preserves the actual positive interaction without denying reciprocal biology or the authors' ligand terminology. (PMID:1386409, original pages 505–507 and Figure 4.)
The later full JEM study directly measures human CD21 D1–2 binding to human CD23 by SPR and NMR mapping. The reported affinity is 0.87 ± 0.09 µM for the tested fragments; calcium removal does not change the measured CD21 interaction. The IgE and CD21 sites on CD23 are distinct. A ternary arrangement bridged by CD23 does not establish direct CR2–IgE binding, and the Fc-gamma-RI-binding child of GO:0034987 does not fit CD23. (PMID:16172256, binding Results/Figure 1, mapping/Figure 4, construct and SPR Methods.)
The original DNA study was read in full main-text scope. Human soluble SCR1–4 and SCR1–15 preparations bind DNA in ELISA/SPR assays with competition controls. However, high nonspecific cell binding “did not allow the reproducible detection of CR2-dependent binding”. The study used 50 mM NaCl and reported no high-affinity DNA binding at 150 mM NaCl. The positive molecular interaction is retained as non-core; it is not a transcription-factor assay, a demonstration of nuclear activity, or proof of physiological surface affinity for every product. (PMID:22885687, Methods, Results and Discussion.)
Original 1991 scans establish IFN-alpha/CR2 binding, competition, Raji-cell binding and proliferation effects. Later human B-cell work reports that anti-CR2 antibody “diminishes the induction of IFN-alpha-responsive genes.” This supports a contextual interferon contribution, with the relationship to IFNAR1/IFNAR2 still unresolved. The 2006 full Methods were not recovered. The protected GO-CAM names MX1 and EIF2AK2 downstream of CR2 and cites the 1991 article for both links, but the original 1991 assays did not measure those named gene-induction readouts. This is a source-scope question, not a reason to erase the positive receptor-associated response. (PMID:1849076, original EMBO Journal pages 919–926; PMID:16785534(https://pubmed.ncbi.nlm.nih.gov/16785534/); GO-CAM 66187e4700002881.)
Selected anti-CR2 antibodies stimulate human B-cell DNA synthesis and later polyclonal immunoglobulin secretion, with T-cell help required. The differentiation row's review excerpt anchors the secretion endpoint; the proliferation and differentiation are retained as contextual downstream outcomes, without a direct cell-cycle or lineage-commitment claim. A B-cell response requiring T-cell help does not itself settle GO:0002456, which refers to an immune response carried out by T cells. (PMID:2995485(https://pubmed.ncbi.nlm.nih.gov/2995485/).)
The EBV gp350/220 literature reports receptor-mediated adsorption, capping and endocytosis. These positive virus-receptor and entry annotations remain non-core host-exploitation functions; they do not require a second normal-host core. The HNRNPU/p120 interaction also remains positive at its reported SCR4-derived binding scope, without converting an abstract's nuclear crosslinker proposal into an established adaptor or transcriptional mechanism. (PMID:3036369(https://pubmed.ncbi.nlm.nih.gov/3036369/); PMID:7753047(https://pubmed.ncbi.nlm.nih.gov/7753047/).)
The selected main PTHR45656 artifacts remain unchanged. Current PANTHER version 19 instead places the exact human 1033-residue target at PTN002499734 in PTHR19325. The target path contains the actual PTN000448838 T-cell/plasma-membrane and PTN008569518 extracellular/classical-complement IBDs, with no intervening loss record. This is an explicit version boundary, not a silent family retargeting. The target's occurrence among descendant support is legitimate evidence, not circularity. Donor count does not determine confidence.
Plasma-membrane localization is supported. Extracellular occurrence is retained as non-core, including actual rat Cr2 descendant evidence and compatible human exosome context; it is not justified merely by having an ectodomain. T-cell immunity and classical-complement inhibition remain UNDECIDED because the specific human participation interpretation is unresolved despite authenticated ancestral placement. The human B-cell complement study positively describes CR2-dependent C3-fragment deposition and compares alternative-only with all-pathway conditions. Those positive results do not prove that CR2 can never inhibit complement in another context. (PMID:11981823(https://pubmed.ncbi.nlm.nih.gov/11981823/).)
Five current ARBA rules match official target cross-references and taxonomy at the recorded branches. This is present-day applicability, not a reconstruction of their historical execution. Both Reactome reactions were traced through actual component objects to human P20023 residues 21–1033 in the plasma membrane: one binds C3 fragments, and the other assembles that complex with CD19:CD81. The three protected GO-CAMs provide complement/B-cell, EBV-entry and interferon curator context; their source attribution is not independent experimental replication.
The homodimerization citation's complete abstract explicitly concerns murine Cr2 glycosylation and structural modeling. Full original Methods were unavailable, leaving the specific human homodimer experiment unresolved. A mouse-focused title is not grounds for a wrong-gene rejection. (PMID:11728339(https://pubmed.ncbi.nlm.nih.gov/11728339/).)
The original PX-FERM trafficking main text and peptide-array figure were read, but the available figure resolution and failed supplement routes did not resolve an exact CR2 peptide-row linkage. Independent human receptor-complex work supports the broad component assertion; it is kept separate from this particular paper. The original human B-cell exosome proteomic main text was also recovered, but the CR2-specific supplementary peptide table was not. The existing positive exosome cargo assertion is retained with curator deference, without an exosome-biogenesis or isoform-specific claim. (PMID:23382219(https://pmc.ncbi.nlm.nih.gov/articles/PMC3581954/); PMID:20458337(https://pubmed.ncbi.nlm.nih.gov/20458337/).)
The official VSP edits reconstruct all four FASTAs exactly: A/P20023-1 is 1033 residues; B/-2 is 1007; C/-3 is 1092; D/-4 is 1084. B deletes canonical residues 499–524 and replaces 525–556. C inserts an additional extracellular repeat segment at canonical 659. D carries that insertion and deletes canonical 716–723. The N-terminal 21–153 region represented in the C3d deposits and the membrane/tail sequence remain, but retention of sequence does not establish equal accessibility, avidity, trafficking or signaling of intact products. The old cloning study's historical precursor length is preserved as reported rather than silently equated with the current displayed product.
The normal provider attempt timed out, and its configured fallback returned an insufficient-quota error. No provider report was fabricated or retried. This journal and its linked source evidence record the manual research, genuine original recoveries and remaining access gaps. Machine-fetched publication, GOA, UniProt, PANTHER and GO-CAM source files were not rewritten to conceal those gaps.
The interferon-associated receptor assertion from PMID:1849076 is retained as non-core, alongside the existing interferon-signaling process. Its positive binding and cellular-response evidence remains; the relationship to canonical IFNAR1/IFNAR2 is still unresolved. The complement/B-cell core is unchanged. The CD23-binding and B-cell-activation refinements intentionally converge on separately retained assertions with distinct source/evidence identities.
The classical-complement inhibition transfer remains UNDECIDED after a targeted mechanistic reassessment. Its on-path ancestral placement is real. The literal donor O02839 is pig CD46, not C4BPA; P04003 is human C4BPA and P17927 is human CR1. Their regulatory evidence does not itself identify the corresponding human CR2 step. The current term definition covers reduction of classical-pathway activation without restricting that reduction to convertase decay.
PMID:2437238, purified CR2 cofactor study reports factor-I-dependent cleavage of membrane-bound iC3b by purified human Raji-cell CR2, with antibody and contamination controls. The complete original printed pp 1424–1429 was read externally, and Figure 2/caption on p 1427 inspected. Its Discussion cautions: “The physiological role of the cofactor function of CR2 has to be determined by further study”. The weak activity does not demonstrate inhibition of the classical pathway, but it rules out asserting that CR2 has never shown any cofactor activity. The abstract-only normal cache remains unchanged.
PMID:31396570, RCA motif study classifies CR2 as non-regulatory, while its actual new activity assays test CR1 constructs and polydom. The relevant original Results and Methods were read; this classification is not a direct new CR2 negative assay. PMID:21452327, soluble CR2 in murine lupus reports lower autoimmune and complement-deposition measures after soluble-CR2 treatment. The Discussion expressly warns that “C1q deposition data do not specifically address classical (or lectin) pathway activation/inhibition”. Its classical-pathway interpretation is indirect, in treated MRL/lpr mice; neither factor-H/Crry fusion activity nor an endogenous human inhibitory mechanism is assigned to CR2. These are concrete unresolved attribution limits, not a claim that an unspecified future context must exist.
The DNA-binding and HNRNPU-binding assertions remain positive and non-core with their original assay/context limits. Receptor-fragment binding is not being promoted to physiological nuclear encounter or all-product equivalence. Actual external full-paper access for PMID:1386409 and PMID:1849076 remains recorded separately from the immutable abstract-only cache flags; no supporting quotation is relabeled as cache-derived. The broad complement-receptor core retains genuine C3d, C3dg and iC3b contexts. See the source evidence for primary locators and the finite follow-up assessment.