id: A0A8C9H4D2 gene_symbol: OLFML2A product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:591936 label: Piliocolobus tephrosceles description: >- OLFML2A (olfactomedin-like 2A, photomedin-1) is a member of the olfactomedin domain protein family (PANTHER PTHR23192, subfamily SF29). The full-length protein is a secreted glycoprotein. It has a signal peptide, two tandem N-terminal CXCXCX9C cysteine motifs, a coiled coil and a C-terminal olfactomedin domain. In mouse it is secreted as a disulfide-linked dimer and binds the sulfated glycosaminoglycans chondroitin sulfate E and heparin. This accession (439 aa) is the short isoform of the Ugandan red colobus gene, corresponding to human isoform 3, which is transcribed from an alternative first exon. It keeps the complete olfactomedin domain but lacks the signal peptide, both cysteine motifs and the coiled coil. Whether this short product is made, and where it is located or what it does, has not been tested. The full-length product of the same gene is A0A8C9H9A8. existing_annotations: - term: id: GO:0005576 label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- Electronic mapping of a UniProt "Secreted" subcellular location, which was assigned to this record by an ARBA rule. Secretion is established for full-length photomedin-1. This accession is the short isoform and has no signal peptide. action: MARK_AS_OVER_ANNOTATED reason: >- The full-length OLFML2A product (A0A8C9H9A8 in this species, Q68BL7-1 in human) is a secreted protein, and extracellular region is correct for the gene. A0A8C9H4D2 starts at an alternative first exon and lacks residues equivalent to human 1-222, so it has no signal peptide. It would not be expected to enter the classical secretory pathway, and there is no evidence that it is released by any other route. The ARBA-derived secretion annotation was applied to this record without considering that the signal peptide is missing. The term should be kept on the full-length product, not on this short isoform. supported_by: - reference_id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-bioinformatics/RESULTS.md supporting_text: >- It retains the complete C-terminal olfactomedin domain but lacks the signal peptide, both CXCXCX9C motifs and the coiled coil. - reference_id: PMID:15836428 supporting_text: >- were secreted as disulphide-bonded dimers (photomedin-1) or oligomers/multimers (photomedin-2) with O-linked carbohydrate chains - term: id: GO:0007165 label: signal transduction evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: involved_in review: summary: >- TreeGrafter transfer of the PAINT signal-transduction placement for the olfactomedin family. The donors behind that node are myocilin and other olfactomedins, not OLFML2A. action: UNDECIDED reason: >- The PAINT IBD for GO:0007165 in PTHR23192 sits at PTN000573635 (Bilateria) and is seeded by MYOC (Q99972) and two mouse olfactomedins. This is a deliberate phylogenetic placement, and OLFML2A (SF29) falls within it. There is no OLFML2A-specific evidence that confirms or refutes inheritance of a signal-transduction role. The only experiments on OLFML2A show secretion, dimerization and glycosaminoglycan binding. The cancer cell-line studies show only correlation or perturbation effects on signaling. In addition, this short isoform lacks the signal peptide that an extracellular signaling role would require. I keep the same UNDECIDED judgment as the human OLFML2A IBA row rather than removing an inherited annotation without evidence against it. supported_by: - reference_id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-bioinformatics/RESULTS.md supporting_text: >- Whether this short transcript is translated, and where the product goes, has not been tested in any species - reference_id: PMID:15836428 supporting_text: >- Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. 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: - statement: >- Full-length mouse photomedin-1 (OLFML2A) has tandem N-terminal CXCXCX9C motifs, a coiled coil and a C-terminal olfactomedin domain. It is secreted as a disulfide-bonded dimer and binds chondroitin sulfate E and heparin. supporting_text: >- characterized by the presence of tandem CXCXCX9C motifs in the N-terminal region, a coiled-coil domain and an olfactomedin domain in the C-terminal region reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- The only direct experimental study of OLFML2A (mouse photomedin-1). The cached record is abstract only. It describes the full-length protein; the N-terminal regions it uses to define photomedins are absent from this short isoform. - id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-bioinformatics/RESULTS.md title: A0A8C9H4D2 gene-model comparison against human OLFML2A and the same-gene full-length product findings: - statement: >- A0A8C9H4D2 is the counterpart of human isoform 3 (Q68BL7-3) and matches it over its full length (97.3% identity). It lacks the region equivalent to human residues 1-222, which contains the signal peptide, both CXCXCX9C motifs and the coiled coil. The full-length product of the same gene is A0A8C9H9A8 (655 aa). supporting_text: >- A0A8C9H4D2 (XP_023072933.1, isoform X2) is the short alternative-first-exon isoform of Piliocolobus OLFML2A, the counterpart of human isoform 3. - id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-uniprot.txt title: UniProt record A0A8C9H4D2 findings: [] - id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-deep-research-falcon.md title: Falcon deep research for A0A8C9H4D2 (OLFML2A) findings: [] reference_review: relevance: LOW correctness: LOW_QUALITY review_notes: >- This is a gene-level literature summary built mainly from human cancer cell-line perturbation studies. It does not notice that this accession is the short isoform without a signal peptide. It was not used as support for any annotation decision. core_functions: - description: >- Retains the complete olfactomedin domain of photomedin-1. For the full-length secreted OLFML2A protein, the established activity is binding of sulfated extracellular glycosaminoglycans (chondroitin sulfate E, heparin). It is not known whether this short isoform, which lacks the signal peptide and the N-terminal dimerization-motif region, is made or has this activity. molecular_function: id: GO:0050840 label: extracellular matrix binding 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/A0A8C9H4D2/A0A8C9H4D2-uniprot.txt record_section: ["DR:PANTHER"] supporting_text: PANTHER; PTHR23192:SF29; OLFACTOMEDIN-LIKE PROTEIN 2A; 1. - reference_id: file:9PRIM/A0A8C9H4D2/A0A8C9H4D2-bioinformatics/RESULTS.md supporting_text: >- It retains the complete C-terminal olfactomedin domain but lacks the signal peptide, both CXCXCX9C motifs and the coiled coil. suggested_questions: - question: >- Is the short alternative-first-exon OLFML2A transcript (human isoform 3, Piliocolobus XP_023072933.1) translated? If so, where does the signal-peptide-less product go, and does its olfactomedin domain alone bind chondroitin sulfate E or heparin? - question: >- Should the ARBA "Secreted" rule exclude UniProt records that lack a predicted signal peptide, such as this N-terminally truncated isoform? suggested_experiments: - hypothesis: >- The olfactomedin domain alone, as encoded by the short isoform, is not secreted but keeps glycosaminoglycan-binding activity. description: >- Express tagged full-length and short-isoform OLFML2A in HEK293 cells. Compare intracellular and conditioned-medium fractions under non-reducing and reducing SDS-PAGE, and test purified olfactomedin-domain protein for binding to chondroitin sulfate E and heparin by solid-phase assay. experiment_type: biochemical localization and binding assay