Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Method for transferring manual annotations to an entry based on a curator's judgment of its similarity to a putative ortholog which has annotations with experimental evidence. Annotations are created when a curator judges that the sequence of a protein shows high similarity to another protein that has annotation(s) supported by experimental evidence (IDA, IGI, IMP, IPI or IEP). Annotations resulting from the transfer of GO terms display the 'ISS' evidence code and include an accession for the protein from which the annotation was projected in the 'with' field (column 8). This field can contain either a UniProtKB Accession or an IPI (International Protein Index) identifier. Only annotations with an experimental evidence code and which do not have the 'NOT' qualifier are transferred. Orthologs/homologs are chosen following a protein MPsrch (http://www.ebi.ac.uk/MPsrch) or BLAST, where the aligned sequences show a high degree of similarity over their entire lengths, making it reasonable to infer that the two proteins have a common function. It must be emphasized that curators must check each alignment and use their experience to assess whether similarity is considered to be strong enough to project annotations. While there is no fixed cut-off point in percentage sequence similarity, generally proteins which have greater than 60% identity that covers greater than 80% of the length of both proteins are examined further. For mammalian proteins this cut-off tends to be higher, with an average of 80% identity over 90% of the length of both proteins. Additional tools, such as the HCOP orthology tool (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/hcop.pl ), are used when possible. Strict orthologs are desirable but not essential. When there is evidence of paralogs, annotations are transferred only to the most similar protein in each species. Further detailed information on this procedure, including how ISS annotations are made to protein isoforms, can be found at: http://www.ebi.ac.uk/GOA/ISS_method.html.