CSF2RA is the ligand-recognizing alpha chain of the GM-CSF receptor. Human alpha alone binds GM-CSF; alpha and the common beta chain reconstitute high-affinity binding. Alpha-interface mutations also impair productive signaling, so its role includes ligand recognition and receptor assembly rather than intrinsic kinase catalysis. The compact core combines GO:0004901, GO:0038157, plasma membrane and the GM-CSF receptor complex. No new assertion is proposed. PMID:2555171(https://doi.org/10.1002/j.1460-2075.1989.tb08541.x), “specificity for human GM-CSF”; PMID:1702217(https://doi.org/10.1073/pnas.87.24.9655); PMID:27396825(https://doi.org/10.1016/j.str.2016.05.017), “interactions playing a major role in receptor signaling”.
The two early originals were recovered as authentic page scans and read by the independent core reviewer. The owner independently read the 2016 indexed Results/Methods and supplemental construct, binding and proliferation methods. The engineered crystallographic ectodomain (mature L1–G301 with three glycosylation-site mutations, expressed in Sf21) is not an official soluble splice product. The full ternary alpha arrangement combines resolved coordinates and modeling; it does not establish one obligatory native oligomeric state. For PMID:18692472 the main article remained unavailable, but authentic publisher supplemental Methods, captions, tables and the independent reviewer's S5/S6 image inspection establish JAK2/STAT5 assay context and receptor-dependent colony assays. JAK2 association with beta is distinct from intrinsic alpha kinase activity. The original abstract-only repository caches remain unchanged. 2008 supplemental data, Methods and Figures S5–S6; 2016 supplemental information, protein expression, ligand binding and proliferation methods.
All eight official products reconstruct exactly from the displayed P15509 sequence and literal VSP edits, at 400, 410, 333, 286, 377, 233, 434 and 267 residues. Their machine-sourced identifiers, descriptions and sequence-edit identifiers are preserved. Sequence reconstruction is not a functional-equivalence experiment. Curated functional classes separately describe the two tested membrane-tail forms, the soluble binding form and the Alu-insertion form.
The owner personally read all five original pages of PMID:1715577 (7744–7748). A human 410-residue alternate-tail construct binds ligand and supports growth in transfected mouse FDC-P1 cells, at relatively high ligand concentrations. Natural coexpression of transcripts does not establish a distinct endogenous signaling program. PMID:1715577(https://pmc.ncbi.nlm.nih.gov/articles/PMC52379/), “This receptor bound ligand and was functionally active”.
The owner personally read all five pages of PMID:1832774 (8203–8207), including Figure 1 and binding experiments. Human soluble cDNA expressed in murine cells produces conditioned-medium GM-CSF binding with little surface binding. Its 16-residue terminal sequence matches official isoform 3. The current official 333-residue sequence is retained despite historical length arithmetic. Conditioned-medium binding did not reach saturation, and physiological antagonism was proposed rather than demonstrated. The extracellular-region assertion is retained as non-core at this soluble-product scope. PMID:1832774(https://pmc.ncbi.nlm.nih.gov/articles/PMC52475/), “bind GM-CSF in solution”.
The complete PMID:17681666 abstract supports preserved binding and enhanced ectodomain release for the 34-residue Alu insertion carried by official isoform 7. Its full Methods/Results were not recovered; no precise native cleavage product or protease activity is assigned to CSF2RA. PMID:8086503 is transcript evidence only; its historical predicted soluble length differs from current isoform 4, and no exact whole-construct or activity equivalence is asserted. Other shortened products remain functionally unresolved. PMID:17681666(https://doi.org/10.1016/j.exphem.2007.06.008), “preferentially targeted by ectodomain proteases”; PMID:8086503(https://pubmed.ncbi.nlm.nih.gov/8086503/).
The literal source assertions are preserved. Current UniProt and protected PANTHER cache metadata name PTHR23037; the v19 gene-information route resolves the exact 400-residue target to PTHR23036, whose 808-node tree contains PTN002507105 below all three seeded ancestors. These are distinct versioned observations. The separate 394-node PTHR23037 API response does not establish evolutionary loss. The current IBD snapshot places genuine GHR-supported growth-hormone activity, pathway and complex terms at on-path PTN002745520. Their removal challenges ligand and complex specificity across the descendant branches, not node existence, donor count or the validity of GHR experiments. Human CSF2RA recognizes GM-CSF in an alpha/common-beta complex, not the specified GH-binding homomeric complex.
The cytosol inference remains UNDECIDED. Bovine GHR's PMID:16174355 abstract reports membrane and cytoplasmic staining; the full localization assay was not recovered, so neither the narrower cytosol compartment nor transfer to CSF2RA is resolved. The saved source is EuropePMC JSON despite a historical .xml filename. The positive JAK-STAT regulatory inference remains supported by independent target experiments. Peptide-hormone binding is refined to cytokine binding without asserting that the categories are mutually exclusive or that one is an is_a child of the other. Exact GO:0017046 IBD is absent only from the captured current snapshot; the literal GOA assertion remains intact. All 35 cytokine-binding children were examined: GO:0042021 explicitly binds a GM-CSF complex and is not silently reinterpreted as simple GM-CSF ligand binding. PMID:16174355(https://pubmed.ncbi.nlm.nih.gov/16174355/); cytokine-binding definition.
InterPro IPR003532 validly supplies broad receptor and membrane terms; target experiments justify the narrower receptor and plasma-membrane replacements. ARBA00028236 branch 0 matches IPR013783, official PTHR23037 and Primates. ARBA00027801 currently has no matching branch among 686, with IPR052672 absent from the closest branch. The combined plasma-membrane assertion also has the independently valid SL-0039 source, so rule-version uncertainty is not turned into a localization rejection. Current source snapshots do not reconstruct historical curator sessions.
Three complete positive IntAct records link human CSF2RA and FATE1 in yeast two-hybrid formats. All 42 fields and six participant sequence checks are retained. The full original screen Methods/Results were read, but study-wide orthogonal validation of subsets is not assigned to this specific pair. The standing CLINGEN_MENDELIAN instruction retains supported generic binding as non-core when no informative specific replacement is established. No FATE1 receptor-regulatory or adaptor mechanism is inferred. PMID:25416956(https://pubmed.ncbi.nlm.nih.gov/25416956/).
All 26 annotated Reactome events have explicit component/member paths to P15509 at the plasma membrane (54 paths across 352 retrieved objects). This validates each original location assertion; associated kinase, phosphatase, adaptor and GEF activities are not transferred to CSF2RA. The surfactant-related event models are distinguished from the primary PAP experiments. Human deletion and G174R studies measure defective receptor expression, clearance and signaling, not purified CSF2RA–surfactant binding. G174R changes glycosylation/apparent mass; cached model wording about truncation is not adopted. The deletion also affects IL3RA. PMID:18955567(https://pubmed.ncbi.nlm.nih.gov/18955567/); PMID:18955570(https://pubmed.ncbi.nlm.nih.gov/18955570/), “GM-CSF-dependent functions in primary myeloid cells”.
The structured evidence index is a manually compiled provenance artifact, not a provider result or primary source. It separates literal source objects and records from review decisions, describes access and construct limits, and records the selected cache hashes. Existing source bytes are retained where present; genuine fetch variants remain separately archived. Default Falcon timed out and the configured fallback returned an authentication failure; no provider synthesis was fabricated. The review instead uses the explicitly recorded manual reads and attributed independent consultations.
Remaining questions concern physiological soluble-receptor effects, signaling competence of the lesser-characterized products and whether a defined intracellular CSF2RA pool supports the cytosol inference. Necessity in surfactant homeostasis is not used to invent a direct surfactant-binding activity or an additional process assertion.
PR #4980 review items 1–2 prompted a distinction between direct alpha-chain cytokine binding and its contribution to cooperative GM-CSF receptor activity. The existing human receptor expression, binding and mutagenesis evidence (PMID:2555171, PMID:1702217, PMID:27396825) supports both ligand recognition and productive receptor assembly. The alpha chain is not merely passive, and neither chain is assigned intrinsic kinase activity. The core uses cytokine binding plus contributes_to receptor activity; the external side of plasma membrane specifies the ligand-recognition site. Source qualifiers remain unchanged.
The cytosol IBA remains UNDECIDED. Its on-path IBD is real, but an intracellular pool is not evidence of activity there. The unresolved issue is the CSF2RA product and site of activity, not just access to the bovine GHR paper. The newly cached and PubMed-checked PMID:16174355 is donor context, with full text unavailable; ligand divergence alone does not prove a compartment was lost.
The peptide-hormone-binding and broad proliferation/location refinements reconcile individual source assertions to already retained terms; they add no NEW rows. Reviewer-access flags and cache-coverage flags describe different things. The existing source index includes original scan URLs and hashes for all five pages of each isoform paper and the independent primary-read records for the other originals; the reference notes now link those sections explicitly. A suggested question records the plain GM-CSF-binding ontology gap without inventing an identifier.