id: A0A8C9H9A8 gene_symbol: OLFML2A product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:591936 label: Piliocolobus tephrosceles description: OLFML2A (olfactomedin-like 2A, photomedin-1) of the Ugandan red colobus is a predicted secreted glycoprotein of 655 residues with an N-terminal signal peptide, two N-terminal CXCXCX9C cysteine motifs, a central low-complexity region and a C-terminal olfactomedin domain. It is the ortholog of human OLFML2A and mouse photomedin-1 (PANTHER subfamily PTHR23192:SF29). The mouse ortholog is secreted as a disulfide-linked homodimer and binds the sulfated glycosaminoglycans chondroitin sulfate E and heparin, consistent with an extracellular protein that associates with proteoglycan-containing matrix. No experiment has been performed on the red colobus protein; its functions are inferred from these orthologs, and a specific matrix-organizing or signaling role has not been established for any OLFML2A ortholog. existing_annotations: - term: id: GO:0005576 label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0243 review: summary: OLFML2A is a secreted extracellular protein; the red colobus sequence carries a predicted signal peptide and is the SF29 ortholog of experimentally secreted mouse photomedin-1. action: ACCEPT reason: The UniProt "Secreted" subcellular location on this entry is an ARBA rule prediction and is not used as support. Independent support comes from the SignalP signal peptide (1..27) on the target and from the experimental secretion of the mouse ortholog photomedin-1, which shares PANTHER subfamily PTHR23192:SF29 and 84% identity over 99% of the target. The PAINT extracellular-region IBD at PTN000573635 also includes mouse Olfml2a among its experimental seeds. This is the right level of specificity for a located_in assertion; a more specific matrix location is proposed separately. supported_by: - reference_id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-uniprot.txt record_section: ["FT:SIGNAL"] supporting_text: SIGNAL 1..27 - reference_id: PMID:15836428 supporting_text: These proteins, named photomedin-1 and photomedin-2, were secreted as disulphide-bonded dimers (photomedin-1) or oligomers/multimers (photomedin-2) with O-linked carbohydrate chains - reference_id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-bioinformatics/RESULTS.md supporting_text: All four proteins are classified in the same PANTHER subfamily, PTHR23192:SF29 - term: id: GO:0007165 label: signal transduction evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: involved_in supporting_entities: - PANTHER:PTN000573918 review: summary: TreeGrafter transfer of a family-level signaling assertion; no OLFML2A ortholog has evidence for a signaling mechanism. action: UNDECIDED reason: This annotation descends from the PAINT IBD for GO:0007165 at the bilaterian node PTN000573635, whose experimental seeds are MGI:1202864, MGI:1860437 and myocilin (UniProtKB:Q99972); mouse Olfml2a (MGI:2444741) is a seed for the extracellular-region IBD at the same node but not for signal transduction. The experiments on the mouse ortholog establish secretion, dimerization and glycosaminoglycan binding, not participation in a signaling pathway. There is equally no evidence that OLFML2A lost the ancestral property, so the node placement cannot be refuted here. Retained as UNDECIDED, consistent with the human OLFML2A review, pending evidence that an OLFML2A ortholog acts in a defined signaling mechanism. supported_by: - reference_id: PMID:15836428 supporting_text: Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. - term: id: GO:0050840 label: extracellular matrix binding evidence_type: ISS original_reference_id: PMID:15836428 qualifier: enables review: summary: Proposed by ortholog inference from mouse photomedin-1, which binds chondroitin sulfate E and heparin. action: NEW reason: Mouse photomedin-1 (Q8BHP7) was tested against a panel of ECM components and bound chondroitin sulfate E and heparin; MGI annotates it to extracellular matrix binding by IDA. The red colobus protein is in the same PANTHER subfamily (PTHR23192:SF29), 84% identical to mouse and 97.5% to human OLFML2A over essentially its full length, and conserves the olfactomedin-domain cysteines and the N-terminal CXCXCX9C motifs, so this is an ortholog-level inference, not an experimental result in this species. The human ortholog carries the same term by Ensembl Compara transfer. PAINT did not propagate this term to the deep family node, which is a judgement about the olfactomedin family as a whole rather than about the OLFML2A subfamily. More specific glycosaminoglycan-binding terms (heparin binding, chondroitin sulfate binding) could be considered once the binding has been examined beyond the original screen. supported_by: - reference_id: PMID:15836428 supporting_text: Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. - reference_id: PMID:15836428 supporting_text: photomedins are novel olfactomedin-domain-containing extracellular proteins capable of binding to proteoglycans containing these glycosaminoglycan chains - reference_id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-bioinformatics/RESULTS.md supporting_text: All four proteins are classified in the same PANTHER subfamily, PTHR23192:SF29 - term: id: GO:0031012 label: extracellular matrix evidence_type: ISS original_reference_id: PMID:15836428 qualifier: located_in review: summary: Proposed by ortholog inference; mouse photomedin-1 was identified in a screen for ECM proteins and binds matrix glycosaminoglycans. action: NEW reason: MGI annotates mouse Olfml2a as located in extracellular matrix by IDA from the photomedin study and the follow-on ECM screen. Together with the glycosaminoglycan binding and secretion data this supports matrix association of the red colobus ortholog, inferred through SF29 orthology. The location claim does not imply a structural or matrix-assembling activity. supported_by: - reference_id: PMID:15836428 supporting_text: We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins - reference_id: PMID:15836428 supporting_text: photomedins are novel olfactomedin-domain-containing extracellular proteins capable of binding to proteoglycans containing these glycosaminoglycan chains references: - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000118 title: TreeGrafter-generated GO annotations findings: [] - id: PMID:15836428 title: 'Identification and characterization of photomedins: novel olfactomedin-domain-containing proteins with chondroitin sulphate-E-binding activity.' full_text_unavailable: true findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Primary characterization of mouse photomedin-1 (Olfml2a, Q8BHP7); abstract cached. Source of the MGI IDA/IPI annotations for the mouse ortholog (QuickGO, checked 2026-10-21). Experimental organism is mouse, not red colobus. - id: PMID:18757743 title: Transcriptome-based systematic identification of extracellular matrix proteins. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Mouse ECM screen cited by MGI for Olfml2a ECM location and ECM organization; the cached abstract does not name Olfml2a, so it is not used as direct support here. - id: PMID:22913984 title: Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Shows Olfml2a expression in podocyte major processes (expression/localization only); not used to support a function. - id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-uniprot.txt title: 9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-uniprot.txt findings: [] - id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-bioinformatics/RESULTS.md title: 'OLFML2A (Piliocolobus tephrosceles, A0A8C9H9A8): ortholog comparison' findings: [] core_functions: - description: Secreted olfactomedin-domain protein that binds sulfated glycosaminoglycans (chondroitin sulfate E, heparin) of the extracellular matrix, inferred from the experimentally characterized mouse ortholog photomedin-1 within PANTHER subfamily PTHR23192:SF29; not tested in this species, and the downstream matrix-organizing consequence is unknown. molecular_function: id: GO:0050840 label: extracellular matrix binding locations: - id: GO:0031012 label: extracellular matrix supported_by: - reference_id: PMID:15836428 supporting_text: Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. - reference_id: file:9PRIM/OLFML2A__A0A8C9H9A8/OLFML2A__A0A8C9H9A8-bioinformatics/RESULTS.md supporting_text: All four proteins are classified in the same PANTHER subfamily, PTHR23192:SF29 suggested_questions: - question: Does OLFML2A participate in any defined signaling mechanism, as implied by the family-level PAINT signal transduction assertion seeded from noelins and myocilin, or is its role limited to glycosaminoglycan/matrix binding? - question: Which proteoglycans carry the chondroitin sulfate E and heparan/heparin chains that OLFML2A binds in vivo (for example in retinal photoreceptor outer segments or podocyte major processes)? suggested_experiments: - description: Express recombinant red colobus or human OLFML2A, confirm secretion and disulfide-linked dimerization, and measure binding affinity to chondroitin sulfate E, heparin and heparan sulfate by surface plasmon resonance, with the olfactomedin domain and N-terminal CXCXCX9C region tested separately.