OLFML2A

DOMAIN ARCHITECTURE MISMATCH

Review rationale: Extracellular matrix is correct for full-length OLFML2A: mouse photomedin-1 (Q8BHP7, same PANTHER subfamily PTHR23192:SF29) is experimentally secreted and binds chondroitin sulphate-E and heparin (PMID:15836428), and the review of the full-length red colobus product A0A8C9H9A8 proposes this location. This accession, however, is the short isoform that starts at an alternative first exon and lacks the region carrying the signal peptide, both CXCXCX9C motifs and the coiled coil. Without a signal peptide it is not expected to enter the classical secretory pathway, and there is no evidence of release by another route. The gene review marks the parent location, extracellular region (GO:0005576, an ancestor of GO:0031012 by OLS4), as over-annotated on this product for that reason, which equally refutes the more specific matrix location. The prediction transfers a full-length-protein property to a product lacking the required targeting segment. The term is absent from GOA for both products of the gene, so it would have been novel.

Review rationale: This accession is the 439-residue short isoform that starts at an alternative first exon (counterpart of human isoform 3). Its residues 9-439 align to residues 225-655 of the full-length product of the same gene, A0A8C9H9A8, which carries a SignalP signal peptide at 1-27; A0A8C9H4D2 has no counterpart of that region and so lacks the signal peptide, both CXCXCX9C motifs and the coiled coil, and is not expected to enter the classical secretory pathway. That absence does not settle the process term, because no mechanism of OLFML2A participation in extracellular matrix organization has been demonstrated, so it cannot be shown that the missing segment accounts for that participation, and no experiment refutes a contribution by this product. The only experimental basis is an MGI IDA annotation of mouse Olfml2a (Q8BHP7, PTHR23192:SF29) with the acts_upstream_of_or_within qualifier, from a systematic screen of candidate secreted proteins for matrix-assembling activities (PMID:18757743), which the mouse review leaves UNDECIDED because the Olfml2a-specific result is not visible. Secretion and glycosaminoglycan binding of full-length photomedin-1 (PMID:15836428) make a matrix role plausible for the full-length product, but no assembly result exists for any ortholog. Whether this short product is translated or released has not been tested. The prediction can be neither validated nor refuted. Neither product of the gene carries the term in GOA.