OLFML2A (olfactomedin-like protein 2A, photomedin-1) is a secreted, O-glycosylated glycoprotein of 652 residues with an N-terminal signal peptide, cysteine-rich CXCXCX9C motifs, a coiled-coil segment, a Ser/Thr-rich low-complexity linker and a C-terminal olfactomedin (OLF) domain. With its paralog OLFML2B (photomedin-2) it forms a distinct olfactomedin subfamily. The characterized mouse ortholog is secreted as a disulfide-linked homodimer that is proteolytically processed in the middle of the molecule after secretion, and it binds sulfated glycosaminoglycans, preferentially chondroitin sulfate E and heparin, so it is thought to associate with proteoglycan-rich extracellular matrix. It is expressed in retinal photoreceptors (mouse) and, in kidney, by podocytes, where it localizes to the major processes. No catalytic activity, receptor or specific signaling pathway has been established; cancer studies report AP-1-dependent expression and expression-prognosis associations rather than a molecular mechanism.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: OLFML2A is a secreted extracellular protein. Reason: The PAINT node PTN000573635 is the bilaterian root of the olfactomedin family, and extracellular localization is shared by its experimentally characterized members. OLFML2A sits within that clade (PANTHER PTHR23192:SF29), carries a signal peptide, and its mouse ortholog in the same subfamily was shown experimentally to be secreted. The family-level inference is consistent with the subfamily-specific evidence. Supporting Evidence: PMID:15836428 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 PMID:15836428 We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins file:human/OLFML2A/OLFML2A-uniprot.txt DR Pfam; PF02191; OLF; 1. file:human/OLFML2A/OLFML2A-uniprot.txt FT SIGNAL 1..27 |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: OLFML2A is a secreted extracellular protein. Reason: The UniProt "Secreted" subcellular location is curated by similarity to mouse Olfml2a (Q8BHP7, same PANTHER subfamily SF29), whose secretion was shown experimentally, and the human protein has a predicted signal peptide. Consistent with the IBA and ISS rows for the same term. Supporting Evidence: PMID:15836428 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 PMID:15836428 We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins file:human/OLFML2A/OLFML2A-uniprot.txt DR Pfam; PF02191; OLF; 1. file:human/OLFML2A/OLFML2A-uniprot.txt FT SIGNAL 1..27 |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | ACCEPT | Summary: OLFML2A is a secreted extracellular protein. Reason: Manual transfer from mouse Olfml2a (Q8BHP7), a one-to-one ortholog in the same PANTHER subfamily (PTHR23192:SF29), which was experimentally shown to be secreted as disulfide-linked dimers. Supporting Evidence: PMID:15836428 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 PMID:15836428 We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins file:human/OLFML2A/OLFML2A-uniprot.txt DR Pfam; PF02191; OLF; 1. file:human/OLFML2A/OLFML2A-uniprot.txt FT SIGNAL 1..27 |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | UNDECIDED | Summary: Family-root IBA for signal transduction; no OLFML2-subfamily evidence for or against it. Reason: The IBD was placed at PTN000573635, the bilaterian root of PTHR23192, from three donors, human myocilin (UniProtKB:Q99972) and two mouse genes, one of which (MGI:1202864) also seeds the myocilin-specific node PTN002754680, so the signaling evidence comes from outside the OLFML2 subfamily. OLFML2A is inside the clade that inherits the node, so the inference is formally valid, and there is no evidence of loss in the OLFML2 subfamily. Equally, no experiment on OLFML2A or OLFML2B connects them to a signal transduction mechanism; the only signaling data (AP-1 regulation of OLFML2A expression in breast cancer cells) place OLFML2A downstream of a transcription factor, not as a participant in signal transduction. The PAINT curators placed other myocilin-derived terms (Golgi, osteoblast differentiation) at the myocilin node only, so the root placement of this broad term was deliberate. Without subfamily evidence the claim can be neither confirmed nor refuted for OLFML2A. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000573635 UNRESOLVED Bilaterian root node of PTHR23192 carrying the signal transduction IBD; OLFML2A (SF29) descends from it. No evidence of loss in the OLFML2 subfamily, but no subfamily-level experimental support either. UniProtKB:Q99972 UNRESOLVED Human myocilin, a donor from a different subfamily; supports the ancestral placement but not specifically OLFML2A. Supporting Evidence: PMID:15836428 Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Photomedin-1 is an ECM-associated extracellular protein. Reason: Ensembl Compara transfer from mouse Olfml2a (same PANTHER subfamily SF29), which was identified in a screen for novel ECM proteins with recombinant expression and immunohistochemistry, and which binds proteoglycan glycosaminoglycan chains. ECM association is a reasonable location; it does not imply a structural matrix role. Supporting Evidence: PMID:15836428 We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins PMID:15836428 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 PMID:15836428 Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Photomedin-1 forms disulfide-linked homodimers. Reason: Mouse photomedin-1 is secreted as a disulfide-bonded dimer, and UniProt curates human OLFML2A as a homodimer by similarity. This is a real property of the assembly state, transferred within the SF29 subfamily, but it is an architectural feature rather than the protein's principal extracellular binding activity. Supporting Evidence: PMID:15836428 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 file:human/OLFML2A/OLFML2A-uniprot.txt CC -!- SUBUNIT: Homodimer. Binds to heparin and chondroitin sulfate E. |
| GO:0050840 extracellular matrix binding | IEA GO_REF:0000107 | ACCEPT | Summary: Photomedin-1 binds glycosaminoglycan components of the ECM. Reason: Ensembl Compara transfer of the MGI IDA from PMID:15836428 on the SF29 mouse ortholog. Among a panel of ECM components the photomedins bound chondroitin sulfate E and heparin. The glycosaminoglycan terms (heparin binding, chondroitin sulfate binding) are not is_a descendants of extracellular matrix binding, so this term is kept as a correct description and the specific ligands are proposed as separate NEW annotations. Supporting Evidence: PMID:15836428 Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. file:human/OLFML2A/OLFML2A-uniprot.txt CC -!- SUBUNIT: Homodimer. Binds to heparin and chondroitin sulfate E. |
| GO:0035374 chondroitin sulfate binding | ISS PMID:15836428 Identification and characterization of photomedins: novel ol... | NEW | Summary: Binds chondroitin sulfate E, its preferred glycosaminoglycan ligand. Reason: Mouse Olfml2a (Q8BHP7, PANTHER SF29 one-to-one ortholog) binds chondroitin sulfate E preferentially among tested ECM components; UniProt curates the human protein accordingly by similarity. This is the most specific ligand-binding activity known for the protein and is more informative than extracellular matrix binding. The OLF domain is conserved, and the human and mouse proteins are in the same subfamily. Supporting Evidence: PMID:15836428 Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. file:human/OLFML2A/OLFML2A-uniprot.txt CC -!- SUBUNIT: Homodimer. Binds to heparin and chondroitin sulfate E. |
| GO:0008201 heparin binding | ISS PMID:15836428 Identification and characterization of photomedins: novel ol... | NEW | Summary: Binds heparin. Reason: The same binding panel on the SF29 mouse ortholog showed heparin as the second preferred glycosaminoglycan ligand, and UniProt curates heparin binding for the human protein by similarity to Q8BHP7. Supporting Evidence: PMID:15836428 Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. file:human/OLFML2A/OLFML2A-uniprot.txt CC -!- SUBUNIT: Homodimer. Binds to heparin and chondroitin sulfate E. |
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Download this section (compressed HTML)Q: Does human OLFML2A bind chondroitin sulfate E and heparin with affinities comparable to the mouse protein, and which region (OLF domain or N-terminal cysteine-rich/coiled-coil region) mediates glycosaminoglycan binding?
Q: Is the family-root IBA for signal transduction (PTN000573635) justified for the OLFML2 subfamily, given that its donors derive from the myocilin subfamily?
Experiment: Quantitative binding (SPR or glycan microarray) of purified human OLFML2A and its post-secretion cleavage fragments to chondroitin sulfate E, heparin and other glycosaminoglycans.
Experiment: Identify native extracellular binding partners of OLFML2A in retina and kidney podocytes by proximity labeling or affinity purification-mass spectrometry.
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