Proteoglycan 3 (eosinophil major basic protein 2, MBP-2), paralog of PRG2/MBP-1, encoded by adjacent gene on chromosome 11q12. Similar structure to PRG2: highly cationic mature protein preceded by acidic glycosylated prosegment. Like PRG2, synthesized as proteoglycan precursor with heavily glycosylated acidic N-terminal domain that neutralizes toxicity during biosynthesis, cleaved to yield active cationic protein. Stored in eosinophil secondary granules. Primary function is antiparasitic and antimicrobial effector via membrane disruption through cationic interactions. Binds heparin and sulfated polysaccharides. Released during eosinophil degranulation in response to helminth infection or allergic inflammation. Cytotoxic to parasites, bacteria, and host cells via membrane permeabilization. Lower expression than PRG2 in eosinophils but similar biological activities. Also triggers mast cell/basophil degranulation and histamine release. Implicated in allergic diseases and asthma pathophysiology. Functions extracellularly after secretion from eosinophil granules. Contributes to host defense against parasitic worms and pathogenic microbes, but also mediates tissue damage in chronic eosinophilic inflammation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006955 immune response | IEA GO_REF:0000002 | ACCEPT | Summary: Immune response - PRG3 is eosinophil immune effector. Reason: Core immune function. Supporting Evidence: file:human/PRG3/PRG3-deep-research-perplexity.md See deep research file for comprehensive analysis file:human/PRG3/PRG3-deep-research-falcon.md PRG3 encodes major basic protein 2 (MBP2), a member of the MBP family of eosinophil granule proteins that adopt a C-type lectin-like fold (lectin-like structural homology rather than canonical Ca2+-dependent lectin activity). The MBP family is best understood as cationic secretory/granule effector proteins that can damage membranes and stimulate immune and stromal cells. |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Carbohydrate binding from UniProt keywords. Per PR #767 review feedback and the falcon deep research, PRG3/MBP2 has lectin-like structural homology rather than canonical Ca2+-dependent lectin activity. Heparin binding is captured by the more specific GO:0008201 elsewhere in this review. Downgraded ACCEPT → MARK_AS_OVER_ANNOTATED. Reason: The lectin-like fold confers structural homology but PRG3 lacks canonical Ca2+-dependent lectin activity; the specific heparin-binding function is already captured by GO:0008201 (heparin binding). |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | REMOVE | Summary: ECM structural constituent - not structural ECM component. Reason: Over-annotation. Supporting Evidence: PMID:28344315 Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | REMOVE | Summary: Extracellular matrix - not ECM structural protein. Reason: Not ECM component. Supporting Evidence: PMID:28344315 Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | REMOVE | Summary: ECM structural constituent - not structural ECM component. Reason: Over-annotation. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | REMOVE | Summary: Extracellular matrix - not ECM structural protein. Reason: Not ECM component. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798745 | ACCEPT | Summary: Extracellular region - PRG3 secreted and functions extracellularly. Reason: Core localization after eosinophil degranulation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798749 | ACCEPT | Summary: Extracellular region - PRG3 secreted and functions extracellularly. Reason: Core localization after eosinophil degranulation. |
| GO:0035580 specific granule lumen | TAS Reactome:R-HSA-6798749 | ACCEPT | Summary: Specific granule lumen - eosinophil secondary granule storage. Reason: Core granule localization. Supporting Evidence: file:human/PRG3/PRG3-deep-research-falcon.md PRG3/MBP2 is localized to the eosinophil secondary (specific) granule, supported by biochemical identification in granule lysates and immunologic localization assays discussed in the foundational characterization/review. |
| GO:1904724 tertiary granule lumen | TAS Reactome:R-HSA-6798745 | REMOVE | Summary: Tertiary granule lumen - eosinophils contain specific/secondary granules, not tertiary granules (neutrophil-specific). Reason: Incorrect granule type. Supporting Evidence: file:human/PRG3/PRG3-deep-research-falcon.md PRG3/MBP2 is localized to the eosinophil secondary (specific) granule, supported by biochemical identification in granule lysates and immunologic localization assays discussed in the foundational characterization/review. |
| GO:0001694 histamine biosynthetic process | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | REMOVE | Summary: Histamine biosynthetic process - MBP2 triggers histamine release from *basophils* (not mast cells) but does not synthesize histamine. Per PR #767 reviewer feedback, the prior MODIFY → GO:0002553 (histamine secretion by mast cell) was the wrong cell type; the basophil-stimulating activity is already captured by the ACCEPTed GO:0045575 (basophil activation) elsewhere in this review. Downgraded to REMOVE. Reason: MBP2 does not biosynthesize histamine; the documented activity is triggering histamine release from basophils, which is fully captured by GO:0045575 (basophil activation) already accepted in this review. No basophil-specific histamine-secretion GO term currently exists, and GO:0002553 (histamine secretion by mast cell) was the wrong cell type. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0017148 negative regulation of translation | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | REMOVE | Summary: Negative regulation of translation - not a documented function of MBP2. Reason: No supporting evidence. Supporting Evidence: PMID:10318872 Analyses of the biological activities showed that hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. file:human/PRG3/PRG3-deep-research-falcon.md No enzymatic activity has been assigned to MBP1 or MBP2, supporting classification as a non-enzymatic effector protein. |
| GO:0019370 leukotriene biosynthetic process | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | REMOVE | Summary: Leukotriene biosynthetic process - MBP2 triggers leukotriene C4 release from basophils but does not synthesize leukotrienes. Parallel to the GO:0001694 (histamine biosynthetic process) fix in the round-2 review: the basophil-triggered LTC4 release is fully captured by GO:0045575 (basophil activation), already ACCEPTed elsewhere in this review. Per round-3 review feedback, action changed MODIFY → REMOVE for consistency. Reason: MBP2 does not biosynthesize leukotrienes; the documented activity is triggering LTC4 release from basophils, which is captured by GO:0045575 (basophil activation) already ACCEPTed in this review. The prior proposed replacement GO:0050729 (positive regulation of inflammatory response) was overly broad. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | ACCEPT | Summary: Positive regulation of interleukin-8 production - stimulates neutrophils to secrete IL-8. Reason: Neutrophil activation effect. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0042119 neutrophil activation | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | ACCEPT | Summary: Neutrophil activation - triggers superoxide production and IL-8 release. Reason: Core immunomodulatory function. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0042554 superoxide anion generation | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | REMOVE | Summary: Superoxide anion generation - PRG3/MBP2 stimulates neutrophils to undergo a respiratory burst (superoxide anion production) but does not itself generate superoxide. Per PR #767 round-4 review feedback, this is the same evidence-mismatch pattern as the round-2/round-3 fixes for GO:0001694 (histamine biosynthetic process) and GO:0019370 (leukotriene biosynthetic process): the stimulation-assay evidence supports a regulator role, not a generator role. Action changed ACCEPT → REMOVE for consistency; the activity is fully captured by GO:0042119 (neutrophil activation), already ACCEPTed in this review. Reason: MBP2 does not itself generate superoxide; the documented activity is triggering neutrophil respiratory burst, which is captured by GO:0042119 (neutrophil activation) already ACCEPTed. Parallel reasoning to the round-2/3 fixes for GO:0001694 and GO:0019370. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0045575 basophil activation | IDA PMID:10318872 A novel and highly divergent homolog of human eosinophil gra... | ACCEPT | Summary: Basophil activation - induces degranulation with histamine and LTC4 release. Reason: Core immunomodulatory function. Supporting Evidence: PMID:10318872 hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. |
| GO:0008201 heparin binding | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: file:human/PRG3/PRG3-uniprot.txt PRG3 is eosinophil granule protein with antimicrobial and antiparasitic activity, similar to PRG2. file:human/PRG3/PRG3-deep-research-falcon.md MBP family proteins interact with heparin/heparan sulfate glycosaminoglycans (GAGs) and may bind cell surfaces via heparan sulfate proteoglycans; these properties are described for MBP/proMBP and used to explain cytotoxic/cytostimulatory mechanisms and receptor engagement. |
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