# HISTORY 07 May 2016: Updated by: TOUCHUP-v1.18 24 Mar 2016: Updated by: TOUCHUP-v1.15 14 Mar 2016: Updated by: TOUCHUP-v1.12 07 May 2016: Updated by: TOUCHUP-v1.18 # molecular_function 20110125: Eukaryota_PTN000026392 has function GTPase activity (GO:0003924) 20110125: Eukaryota_PTN000026392 has function G-protein coupled receptor binding (GO:0001664) 20110125: Eukaryota_PTN000026392 has function signal transducer activity (GO:0004871) 20110125: Eukaryota_PTN000026392 has function G-protein beta/gamma-subunit complex binding (GO:0031683) 20110125: Euteleostomi_PTN000026625 has function G-protein coupled serotonin receptor binding (GO:0031821) 20110125: Bilateria_PTN000026689 has function D5 dopamine receptor binding (GO:0031752) 20110125: Euteleostomi_PTN000026718 has function type 1 angiotensin receptor binding (GO:0031702) 20110125: Deuterostomia_PTN000026844 has function G-protein coupled serotonin receptor binding (GO:0031821) 20140530: Euteleostomi_PTN000026867 has function mu-type opioid receptor binding (GO:0031852) 20140530: Euteleostomi_PTN000026867 has function corticotropin-releasing hormone receptor 1 binding (GO:0051430) 20140530: Euteleostomi_PTN000026793 has function insulin-like growth factor receptor binding (GO:0005159) 20110125: Euteleostomi_PTN000026793 has function ionotropic glutamate receptor binding (GO:0035255) 20140530: Euteleostomi_PTN000026793 has function corticotropin-releasing hormone receptor 1 binding (GO:0051430) 20140530: Euteleostomi_PTN000026793 has function beta-2 adrenergic receptor binding (GO:0031698) 20140530: Euteleostomi_PTN000026793 has function D1 dopamine receptor binding (GO:0031748) 20110125: Euteleostomi_PTN000026793 has function mu-type opioid receptor binding (GO:0031852) 20140530: Tetrapoda_PTN000026401 has function type 2A serotonin receptor binding (GO:0031826) 20110125: Tetrapoda_PTN000026458 has function GTPase activator activity (GO:0005096) 20140530: Tetrapoda_PTN000026458 has function type 2A serotonin receptor binding (GO:0031826) 20110125: Magnoliophyta_PTN000027014 has function GTPase inhibitor activity (GO:0005095) 20110125: Magnoliophyta_PTN000027014 has function channel regulator activity (GO:0016247) # cellular_component 20110125: Eukaryota_PTN000026392 is found in heterotrimeric G-protein complex (GO:0005834) 20110125: Euteleostomi_PTN000026521 is found in photoreceptor outer segment (GO:0001750) 20110125: Euteleostomi_PTN000026521 is found in photoreceptor inner segment (GO:0001917) 20110125: Bilateria_PTN000026689 is found in brush border membrane (GO:0031526) # biological_process 20110125: Eukaryota_PTN000026392 participates in adenylate cyclase-modulating G-protein coupled receptor signaling pathway (GO:0007188) 20110125: Euteleostomi_PTN000026590 participates in adenosine receptor signaling pathway (GO:0001973) 20110125: Euteleostomi_PTN000026590 participates in gamma-aminobutyric acid signaling pathway (GO:0007214) 20110125: Euteleostomi_PTN000026590 participates in adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway (GO:0007193) 20110125: Amniota_PTN000026546 participates in sensory perception of sweet taste (GO:0050916) 20110125: Tetrapoda_PTN000026544 participates in sensory perception of umami taste (GO:0050917) 20110125: Euteleostomi_PTN000026521 participates in detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580) 20110125: Bilateria_PTN000026689 participates in Rho protein signal transduction (GO:0007266) 20110125: Euteleostomi_PTN000026718 participates in adenylate cyclase-activating G-protein coupled receptor signaling pathway (GO:0007189) 20110125: Euteleostomi_PTN000026718 participates in activation of phospholipase D activity (GO:0031584) 20110125: Euteleostomi_PTN000026867 participates in dopamine receptor signaling pathway (GO:0007212) 20110125: Bilateria_PTN000026754 participates in adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191) 20110125: Bilateria_PTN000026754 participates in sensory perception of chemical stimulus (GO:0007606) 20110125: Euteleostomi_PTN000026758 participates in sensory perception of smell (GO:0007608) 20110125: Bilateria_PTN000026396 participates in phospholipase C-activating dopamine receptor signaling pathway (GO:0060158) 20110125: Tetrapoda_PTN000026401 participates in action potential (GO:0001508) 20110125: Tetrapoda_PTN000026458 participates in glutamate receptor signaling pathway (GO:0007215) 20110125: Tetrapoda_PTN000026458 participates in adenylate cyclase-activating G-protein coupled receptor signaling pathway (GO:0007189) 20110125: Tetrapoda_PTN000026458 participates in action potential (GO:0001508) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES . Fast pass curation of PTHR10218 (GTP-BINDING PROTEIN ALPHA SUBUNIT family) Description of phylogeny This is a relatively large family with 342 proteins, ~115 of which are RefGEnome proteins. Fast pass curation will miss some clade-specific details, to be discerned later. The family has 3 successive outgroups: plant, dicty, and fungal G-protein alpha subunits (all numbered). Then, AN3 is a 5-way metazoan polytomy: AN4, AN125, AN297, AN362, and AN437. These are all G-protein alpha subunits. We will crawl these clades for more specific detail later. MF -There are no NOT annotations. -There are widespread annotations to GO:0003924 "GTPase activity" all the way out to plants. There are very few annotations to children of GO:0030695 "GTPase regulator activity." Propagate 3924 to AN0 -Child terms: propagate the following within clade: GO:0005085 "guanyl-nucleotide exchange factor activity" to AN454 GO:0005096 "GTPase activator activity" to AN66 GO:0005095 "GTPase inhibitor activity" to AN622 -Propagate GO:0004016 "adenylate cyclase activity" to AN366. -Propagate GO:0016247 "channel regulator activity" to AN622. -Propagate GO:0004871 "signal transducer activity" to AN0 because these are G protein subunits. There will probably be more informative BP annotations, though. Moving on to binding terms -Propagate GO:0031683 "G-protein beta/gamma-subunit binding" and GO:0001664 "G-protein-coupled receptor binding" to AN0, even though these will probably be handled better by a CC annotation. Technically, 1664 and children should probably have contributes_to modifiers. -Children of 1664: Propagate the following within clade: GO:0031702 "type 1 angiotensin receptor binding" to AN326 GO:0031752 "D5 dopamine receptor binding" to AN297 based on annotations in both rat paralogs Gna12 and Gna13. GO:0031821 "metabotropic serotonin receptor binding" to AN233 based on annotations in both rat paralogs Gnai1 and Gnai3. Also to AN452 based on annotations to both rat paralogs Gnaz and Gnao1. GO:0031852 "mu-type opioid receptor binding" to AN401. -Propagate GO:0035255 "ionotropic glutamate receptor binding" to AN401. CC -Propagate GO:0005834 "heterotrimeric G-protein complex" to AN0. -Propagate GO:0031234 "extrinsic to internal side of plasma membrane" to AN0 pending resolution of ontology question. (Question is: Should 5834 be a child of 31234?) Do not propagate the following related annotations for now: GO:0005938 "cell cortex," GO:0016324 "apical plasma membrane," and GO:0045179 "apical cortex." Also wait to propagate GO:0045121 "membrane raft" and its child GO:0005901 "caveola." -Propagate GO:0031526 "brush border membrane" to AN297 based on annotations to both rat paralogs Gna12 and Gna13 and the MF annotation "type 1 angiotensin receptor binding" on AN326. These are all kidney-related. -Propagate GO:0001750 "photoreceptor outer segment" and GO:0001917 "photoreceptor inner segment" to AN129 based on multiple annotations in GNAT1, 2, and 3 clades. Note that these are children of AN130, but the AN129 outgroup is still vertebrate, and the branch length to it is short. For now, do not propagate GO:0032391 "photoreceptor connecting cilium." -Do not address the following terms remaining: GO:0005634 nucleus GO:0005829 cytosol GO:0031982 vesicle GO:0005768 endosome GO:0043005 neuron projection GO:0030424 axon GO:0043025 neuronal cell body GO:0032153 cell division site GO:0005816 spindle pole body GO:0001669 acrosomal vesicle GO:0042588 zymogen granule BP Start with pathway terms, first with tautological annotations: -Propagate GO:0007188 "G-protein signaling, coupled to cAMP nucleotide second messenger" to AN0 based on multiple annotations. Next with G-protein related annotations: -Propagate GO:0007266 "Rho protein signal transduction" to AN297 based on 4 annotations. Possibly, this should be propagated more broadly. -Do not propagate GO:0046578 "regulation of Ras protein signal transduction," which is only observed in 1 dicty protein in a 13-way polytomy with long branch lengths. -Propagate GO:0007189 "activation of adenylate cyclase activity by G-protein signaling pathway" to AN66 and AN326 based on mouse. Also propagate to AN362 based on annotation to both mouse paralogs Gnal and Gnas. Also propagate to fungal outgroup AN569. -Propagate GO:0007193 "inhibition of adenylate cyclase activity by G-protein signaling pathway" narrowly to Gnai1, -2, and -3 clades (AN198 and AN233) because it is a direct child of 7188). Continue with other important pathways: -Propagate GO:0001973 "adenosine receptor signaling pathway" to AN198. -Propagate GO:0060158 "activation of phospholipase C activity by dopamine receptor signaling pathway" to AN4 based on direct annotations to mouse Gna11 and Gnaq and additional annotations to the parent term GO:0007200 "activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger" on mouse Gna15 and rat Gnaq. Although these annotations only span AN8, the short branch length back to AN4 justifies expanding to the rest of the clade. Also note the annotation to GO:0007212 "dopamine receptor signaling pathway" on worm egl-30. -Propagate GO:0007191 "activation of adenylate cyclase activity by dopamine receptor signaling pathway" to AN362 based on annotations in both mouse paralogs Gnai and Gnas. -Propagate GO:0007212 "dopamine receptor signaling pathway" conservatively to AN475 based on mouse Gnao1, but note the annotation to the worm outgroup protein goa-1. -Propagate GO:0007215 "glutamate signaling pathway" to AN66 based on mouse. -Propagate GO:0007214 "gamma-aminobutyric acid signaling pathway" to AN198 based on rat. Other molecular processes: -Do not propagate GO:0031684 "heterotrimeric G-protein complex cycle" pending resolution of question about its meaning. -Propagate GO:0031584 "activation of phospholipase D activity" from rat to AN326. Taste and smell: -Propagate the parental term GO:0007606 "sensory perception of chemical stimulus" to AN129 and AN362. -Propagate GO:0007608 "sensory perception of smell" to AN366. -Propagate GO:0050909 "sensory perception of taste" to AN129 based on 4 annotations. -Propagate GO:0050913 "sensory perception of bitter taste" to AN129 based on 3 annotations. Propagate GO:0001580 "detection of chemical stimulus involved in sensory perception of bitter taste" to AN129 based on rat Gnat1 and -2. -Propagate GO:0050916 "sensory perception of sweet taste" to AN154 from mouse. -Propagate GO:0050917 "sensory perception of umami taste" to AN152 based on annotations in both mouse paralogs Gnat1 and Gnat3. Sight/rhodopsin: -Propagate GO:0007601 "visual perception" to AN129 based on 6 annotations. -Propagate GO:0007602 "phototransduction" to AN129 based on 3 annotations. -Replace both with the grandchild term GO:0009586 "rhodopsin mediated phototransduction" from rat Gnat1. Other responses to stimuli: Normally, I would ignore most of these as microarray experiments, but G proteins are known for being involved in signal transduction in response to stimuli. After briefly reviewing annotations to GO:0042221 "response to chemical stimulus" and its children and ignoring IEPs and most IMPs, I can see no direct involvement in any response pathways for any member of this family. Misc: -Propagate GO:0051927 "negative regulation of calcium ion transport via voltage-gated calcium channel activity" to AN198 from rat. -Propagate GO:0001508 "regulation of action potential" to AN9 and AN66 from 1 mouse gene each. =Questions for ontology curators= ==Cellular Component== *'''Question: '''Should GO:0005834 "heterotrimeric G-protein complex" be moved down one level, from being a child of GO:0019897 "extrinsic to plasma membrane" to being a child of GO:0031234 "extrinsic to internal side of plasma membrane"? (SF # 3220764) **'''Curator comment: '''I'd say yes, the G protein complex interacts with the cytpoplasmic loops and cytoplasmic end of the transmembrane bundle, never the extracellular loops, so it is more accurate to use the suggested term. **'''Result''': term moved as suggested. ==Biological Process== *'''Question: '''Is the term GO:0031684 "heterotrimeric G-protein complex cycle," defined as "The series of molecular events that generate a signal through the activation of G-protein subunits and recycling of these subunits," intended to refer to the G protein complexes that are cycled or to any external proteins that help them get cycled? **'''Curator answer: '''Insert answer here. MSL 11 Feb 2011 Revised 26 Aug 2011: Questions from wiki added # 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).