# HISTORY 26 Mar 2016: Updated by: TOUCHUP-v1.15 16 Mar 2016: Updated by: TOUCHUP-v1.14 # molecular_function 20140825: Eukaryota_PTN000466746 has function patched binding (GO:0005113) 20140825: Eukaryota_PTN000466746 has function smoothened binding (GO:0005119) # cellular_component 20140825: Eukaryota_PTN000466746 is found in BBSome (GO:0034464) 20140825: Eukaryota_PTN000466746 is found in axoneme (GO:0005930) 20140825: Eukaryota_PTN000466746 is found in centrosome (GO:0005813) 20140825: Eukaryota_PTN000466746 is found in ciliary basal body (GO:0036064) # biological_process 20140825: Eukaryota_PTN000466746 participates in protein localization to cilium (GO:0061512) 20140825: Eukaryota_PTN000466746 participates in cilium assembly (GO:0042384) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES This family contains the BBS1 subunit of the highly conserved seven-member BBSome complex, a membrane coat complex that traffics membrane proteins to the primary cilium (PMID:19575670, PMID:20697559, PMID:20603001). Whether this trafficking occurs by a vesicular mechanism or as a planar patch that moves laterally within the membrane is not yet clear as of August 2014. The BBSome also appears to be an adaptor for some retrograde intraflagellar traffic (IFT) within the cilium (PMID:20697559). Comments on the tree & sequences ---------------------------- This tree looks very straightforward. Both duplication nodes look like sequence issues rather than true duplications: - The two sequences for Macaca mulatta (MACMU_LOC720059 and MACMU_EGK)05964) look like two sequence fragments of the same coding sequence where the former encodes the N-terminal third and the latter encodes the C-terminal two thirds of the protein, with a small gap from about 365 to 400 of the overall alignment. - The three sequences for Pristionchus pacificus (H3E7Q2_PRIPA, H3E7Q3_PRIPA, and H3E7Q4_PRIPA) look like sequence fragments of the same coding sequence. All three are unreviewed Trembl entries. Comments on annotations and propagations ----------------------------------- - I decided not to propagate the MF annotation of the human BBS1 to "RNA polymerse II repressing transcription factor binding (GO:0001103 from PMID:22302990) because this was done by yeast two-hybrid with isolated subunits of the BBSome complex against the RNF2 transcription factor and multiple subunits showed the same effect, suggesting that the interaction might be at the level of the BBSome complex, rather than an individual subunit. In addition, they say that they "have shown recently that depletion of BBS4 results in defective proteasome-mediated protein clearance, leading to the accumulation of β-catenin in BBS4 knockdown cells (Gerdes et al., 2007).", and show similar accumulation of RNF2 protein in BBS knockdown cells. Basically, this seems somewhat preliminary and potentially indirect, so I have not chosen to propagate this annotation. - I decided not to propagate the BP annotation of the human BBS21 to "Golgi to plasma membrane protein transport" from PMID:19150989 because while the authors said "most likely between the Golgi and the ciliary and/or plasma membrane" and thus did not seem certain exactly which membrane is the target of BBSome mediated trafficking. - I did not propagate a large number of BP annotations based on developmental phenotypes because they are all downstream of the primary defect in trafficking to the cilium and the resulting defect in cilary function. # REFERENCE Annotation inferences using phylogenetic trees The goal of the GO Reference Genome Project, described in PMID 19578431, is to provide accurate, complete and consistent GO annotations for all genes in twelve model organism genomes. To this end, GO curators are annotating evolutionary trees from the PANTHER database with GO terms describing molecular function, biological process and cellular component. GO terms based on experimental data from the scientific literature are used to annotate ancestral genes in the phylogenetic tree by sequence similarity (ISS), and unannotated descendants of these ancestral genes are inferred to have inherited these same GO annotations by descent. The annotations are done using a tool called PAINT (Phylogenetic Annotation and INference Tool).