| Aspect | OLFML2A-specific evidence | Inference from related olfactomedin family members | Evidence strength / interpretation |
|---|---|---|---|
| Verified identity | Target protein is annotated in UniProt as **OLFML2A** from *Piliocolobus tephrosceles* and contains **Olfactomedin-like / OLF domains**; human literature also uses the same symbol/name “olfactomedin-like 2A” in breast cancer and disease-association studies (pqac-00000000, pqac-00000009) | OLFML proteins are recognized as a subfamily within the broader olfactomedin family that includes OLFML1/2A/2B/3 (pqac-00000008) | High confidence that the queried protein belongs to the OLFML2A/olfactomedin-like family; species-specific functional data for *P. tephrosceles* are lacking |
| Protein family / structural domains | OLFML2A is identified as an **olfactomedin-domain-containing** protein in Chiari malformation genetics work (pqac-00000009) | OLFML3 is described as a glycoprotein with an **N-terminal coiled-coil region** and **C-terminal OLF-like domain**; OLFML family proteins are glycoproteins within the OLF family, whose members share a conserved C-terminal olfactomedin domain (pqac-00000004, pqac-00000008) | Moderate confidence for domain architecture by homology; direct structural characterization for OLFML2A itself was not found |
| Molecular class | OLFML2A is treated in functional cancer studies as a **regulatory protein** affecting proliferation, apoptosis, migration, invasion, and EMT rather than as an enzyme or transporter (pqac-00000000, pqac-00000002) | Reviews of matricellular proteins describe extracellular regulatory proteins that bind matrix proteins, receptors, cytokines, or proteases; olfactomedin-like proteins are discussed in this extracellular/matricellular context, and OLFM2 is explicitly called a **pleiotropic glycoprotein** and scaffold-like mediator (pqac-00000007, pqac-00000006) | Best current interpretation: **non-enzymatic glycoprotein / likely matricellular regulator** rather than catalyst; no substrate-specific enzymatic activity reported |
| Enzymatic activity / substrate specificity | No evidence in the OLFML2A papers for catalytic activity, reaction chemistry, or substrate transport; studies focus on transcriptional regulation and cell phenotypes after knockdown (pqac-00000000, pqac-00000002) | Related family literature likewise emphasizes signaling, adhesion, migration, immune modulation, and protein-protein interactions rather than enzyme function (pqac-00000004, pqac-00000006, pqac-00000007) | High confidence that OLFML2A is **not currently known as an enzyme**; substrate specificity is **not established** |
| Subcellular localization | Direct localization for OLFML2A was not experimentally established in the retrieved OLFML2A papers; supplemental material points to Human Protein Atlas expression resources for protein distribution (pqac-00000002) | Matricellular proteins are **secreted into the extracellular matrix**; surfaceome-focused screening included extracellular/plasma-membrane-associated proteins, and OLFML3 was identified in that framework; OLFML family proteins are described as extracellular or cell-surface-associated glycoproteins (pqac-00000007, pqac-00000010, pqac-00000008) | Moderate confidence that OLFML2A is **secreted/extracellular ECM-associated** by family-level inference, but direct localization evidence for this specific protein remains limited |
| Primary biological role | In triple-negative breast cancer (TNBC), OLFML2A is required for robust **cell proliferation, migration, invasion, and survival**; its silencing induces **apoptosis**, **cell-cycle arrest**, and suppresses **EMT** (pqac-00000000, pqac-00000002) | Related OLF proteins regulate cell proliferation/migration and tissue remodeling: OLFML3 controls macrophage migration/phagocytosis and mitochondrial immune function, while OLFM2 regulates adipocyte differentiation and focal adhesion-related programs (pqac-00000004, pqac-00000006) | Strongest evidence supports a role as a **context-dependent extracellular/signaling regulator of cell behavior** rather than a structural scaffold alone |
| Cell adhesion / ECM-linked functions | OLFML2A knockdown in TNBC altered pathways including **integrin signaling**, cytoskeleton, cell movement, and EMT-associated programs (pqac-00000002) | Matricellular proteins act through matrix and receptor interactions; olfactomedin family proteins are broadly linked to **cell adhesion** and ECM-mediated signaling; OLFM2 modulates **focal adhesion** pathways (pqac-00000007, pqac-00000006) | Moderate-to-strong evidence for ECM/adhesion-linked regulatory function |
| EMT / invasion | OLFML2A silencing decreases EMT progression and reduces migration/invasion in TNBC cells (pqac-00000000, pqac-00000002) | OLFML2B is associated with EMT, metastasis, immune-suppressive tumor microenvironment, and poor prognosis in lung cancer (pqac-00000008) | Strong cancer-context evidence that OLFML2A-family proteins can promote invasive phenotypes |
| Cell proliferation / survival | OLFML2A knockdown suppresses TNBC proliferation and promotes apoptosis; GeneChip analysis highlighted effects on DNA synthesis, chromosome alignment, microtubules, cytoskeleton, and checkpoint pathways (pqac-00000002) | OLFM2 deficiency impairs adipocyte differentiation and downregulates cell-cycle genes; OLFML3 affects inflammatory survival phenotypes in vivo (pqac-00000006, pqac-00000004) | Strong for growth/survival regulation, especially in transformed cells |
| Signaling pathways: AP-1 | OLFML2A was identified as a **key regulatory protein downstream of AP-1** in TNBC and is required for the anti-tumor effect of the AP-1 inhibitor **T-5224** (pqac-00000000) | AP-1/Fra-1 is a major driver of EMT and metastasis in cancer broadly, fitting the OLFML2A-TNBC phenotype (pqac-00000000) | Strong direct evidence for AP-1-linked regulation in breast cancer |
| Signaling pathways: p53 / DNA damage checkpoint / HGF / NGF / integrin | OLFML2A knockdown was reported to activate **G2/M DNA damage checkpoint regulation** and **p53 signaling** while inhibiting **integrin**, **HGF**, **NGF**, and other tumor-promoting pathways in TNBC cells (pqac-00000002) | Related family members also connect to inflammation, migration, and extracellular communication pathways (pqac-00000004, pqac-00000008) | Moderate-to-strong evidence, but mainly from one transcriptomic perturbation study |
| Signaling pathways: TGF-beta | No direct OLFML2A-TGF-beta mechanistic paper was retrieved here | Related literature summarized in an ophthalmic review states that **OLFML2A is a novel TGF-beta regulator that induces smooth muscle differentiation**; OLFML3 is a direct TGF-beta target gene in microglia (pqac-00000005) | Low-to-moderate confidence for OLFML2A-TGF-beta involvement within this evidence set because the direct primary study was not retrieved |
| Disease / phenotype associations | High OLFML2A expression is associated with **poor prognosis in TNBC**; independent genetic association studies implicate **OLFML2A variants** in **Chiari malformation type I**; cattle GWAS nominate **OLFML2A** as a candidate gene for **milk fat yield** (pqac-00000000, pqac-00000009, pqac-00000003) | Related family members are implicated in lung cancer (OLFML2B), antiviral immunity and acute lung injury (OLFML3), and obesity/adipocyte dysfunction (OLFM2) (pqac-00000008, pqac-00000004, pqac-00000006) | Human disease association is strongest for cancer; non-cancer traits currently remain association-based rather than mechanistically resolved |
| Real-world / current applications | OLFML2A is being discussed as a **potential therapeutic target** and prognostic biomarker in TNBC, especially in AP-1-high disease contexts (pqac-00000000, pqac-00000002) | Family-level applications include biomarker/prognostic studies for OLFML2B in lung cancer and mechanistic targeting concepts for olfactomedin proteins in inflammation and metabolism (pqac-00000008, pqac-00000004, pqac-00000006) | Translational potential is emerging, but no established clinical assay or approved therapy targeting OLFML2A was identified |
| Key caveat for annotation of the Ugandan red colobus protein | No publication directly characterizes **A0A8C9H4D2 OLFML2A in *Piliocolobus tephrosceles***; therefore, functional annotation must rely primarily on conserved domain architecture and mammalian ortholog data (pqac-00000000, pqac-00000009) | Family evidence consistently supports a secreted/extracellular, non-enzymatic regulatory role for OLFML proteins (pqac-00000004, pqac-00000007, pqac-00000008) | Most defensible annotation: **secreted/extracellular olfactomedin-like glycoprotein involved in ECM/cell-signaling regulation, with likely roles in adhesion, migration, and proliferation** |


*Table: This table summarizes the best-supported characteristics of OLFML2A, combining direct evidence for OLFML2A with carefully marked family-based inferences from related olfactomedin proteins. It is useful for functional annotation because species-specific data for the Ugandan red colobus protein are limited.*