# HISTORY
23 Mar 2016: Updated by: TOUCHUP-v1.15
14 Mar 2016: Updated by: TOUCHUP-v1.12

# molecular_function
20110106: Eukaryota_PTN000006939 has function GTPase activator activity (GO:0005096) 

# cellular_component
20140506: Eukaryota_PTN000006939 is found in cytoplasm (GO:0005737) 
20110106: Opisthokonta_PTN000006942 is found in TSC1-TSC2 complex (GO:0033596) 

# biological_process
20110614: Opisthokonta_PTN000006942 participates in negative regulation of TOR signaling (GO:0032007) 
20110615: Bilateria_PTN000006943 participates in regulation of cell cycle (GO:0051726) 
20140506: Bilateria_PTN000006943 participates in negative regulation of protein kinase B signaling (GO:0051898) 
20140506: Bilateria_PTN000006943 participates in negative regulation of insulin receptor signaling pathway (GO:0046627) 
20110614: Bilateria_PTN000006943 participates in negative regulation of Wnt signaling pathway (GO:0030178) 
20140506: Deuterostomia_PTN000006983 participates in activation of GTPase activity (GO:0090630) 

# WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED

# NOTES
Phylogeny
The family spans Tetrahymena to humans, with a duplication at the metazoans giving rise to 2 main clades: TSC2 (Tuberin, Eukaryota_PTN000006939) and some Ran/RapGAP-like proteins.  Actually, the TSC2 clade contains pombe tsc2 and 2 other fungal proteins.  The Tetrahymena and Dicty outgroups are all Ras or Ran/RapGAP-like proteins.  There is an additional duplication among the quadrupeds (PTN001296139), splitting the GAP proteins into an/Rap-like and akt-substrate-like clades.
MF
-Propagate GO:0005096 "GTPase activator activity" to root based on widespread primary annotations.
CC
- Did not annotate to nucleus based on PMID:17114346 that claims that tuberin is mostly cytoplasmic.
- Made annotation to cytoplasm to cover other potential localizations.
BP
-Propagate GO:0007165 "positive regulation of GTPase activity" to root.
-Propagate GO:0032007 "negative regulation of TOR signaling cascade" to entire TSC2 clade (mTOR orthologs found in all opisthokonts, including tor2 in pombe).
-Propagate GO:0046627 "negative regulation of insulin receptor signaling pathway" to Bilateria_PTN000006943 TSC2 (also see PMID:15249583), this annotation is also in Drosophila.
-Propagate GO:0030178 "negative regulation of Wnt receptor signaling pathway" to animal to Bilateria_PTN000006943.
-Propagate cell cycle to Bilateria_PTN000006943 clade, since this is consistent with negative regulation of insulin signaling.
- Do not propagate cell proliferation or regulation of cell size as those are downstream effects of the cell cycle regulation role.
-Do not Propagate GO:0014065 "neg regulation phosphoinositide 3-kinase cascade" as it is indirect.
-Do not Propagate GO:0045449 "regulation of transcription" to AN48 (see Caution in Swiss-Prot record for mouse Garnl1)
-Most remaining terms are developmental.
Fast-pass curation, MSL, 6 Jan 2011
PDT, 14 June 2011
Reviewed PG, 6 May 2014

# 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).