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

# molecular_function
20110614: node_PTN000150817 has function adenosine deaminase activity (GO:0004000) 
20110614: Bilateria_PTN000150875 has function growth factor activity (GO:0008083) 

# cellular_component
20110614: Ascomycota_PTN000150994 is found in nucleus (GO:0005634) 
20110614: node_PTN000150817 is found in cytosol (GO:0005829) 
20110614: Bilateria_PTN000150875 is found in extracellular space (GO:0005615) 
20110614: Euteleostomi_PTN000150944 is found in external side of plasma membrane (GO:0009897) 
20110614: Eukaryota_PTN000150872 is NOT found in cytosol (GO:0005829) 
20110614: Eukaryota_PTN000150819 is NOT found in cytosol (GO:0005829) 

# biological_process
20110614: node_PTN000150817 participates in inosine biosynthetic process (GO:0046103) 
20110614: node_PTN000150817 participates in adenosine catabolic process (GO:0006154) 
20110614: node_PTN000150817 participates in hypoxanthine salvage (GO:0043103) 
20110614: Euteleostomi_PTN000150944 participates in T cell activation (GO:0042110) 
20110614: Euteleostomi_PTN000150944 participates in negative regulation of adenosine receptor signaling pathway (GO:0060169) 
20110614: Eukaryota_PTN000150819 does NOT participate in hypoxanthine salvage (GO:0043103) 

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

# NOTES
- Phylogeny: there are two major clades: an adenosine deaminase (add) and a smaller clade of adenine deaminases (in fungi at least).  The latter clade is small and may have arisen from horizontal transfer events (there also appears to be a potential bacterial contaminant in the Xenopus genome).  In the add clade there are three subclades in eukaryotes: ADA, ADAL, CECR1.  ADAL has no expt annotations, and fly genes in the CECR1 clade have experimental annotations as growth factors.
- Molecular function:
- annotate the MRCA of each of the major clades with add and adenine d, respectively.
- in the CECR1 clade, annotate the animal common ancestor with growth factor, because this activity appears to be present in humans as well as insects: PMID:20453107
- Cellular component:
- adenine d experimental annotations are to cytosol and nucleus; annotate cytosol to MRCA but nucleus only to fungal MRCA to be conservative
- add: annotated cytosol to MRCA of clade based on ADA annotations, but added NOTs to prevent propagation to CECR1 and ADAL clades.
- CECR1 clade: extracellular space is consistent with growth factor activity, and the annotation of fly Msi to membrane should also be extracellular based on the same publication PMID:10967093, so propagate to animal MRCA
- ADA clade: this is extracellular/cell surface in humans and rats, based on interactions with CD26.  Orthologs of CD26 appear across the tree of life, and have potential membrane spanning regions (based on the MSA) in opisthokonts, but based on the T-cell antigen annotation, I will only propagate to the vertebrate MRCA.
- Biological process:
- adenine d: annotate to processes directly related to MF
- add: ADA plus coli add annotations allow annotation of processes directly related to MF (adenosine->inosine)
- ADA: T-cell activation to vertebrate MRCA (see above, molecular target CD26 is known), neg regulation of adenosine receptor signaling pathway to vertebrate MRCA (this is phylogenetic range of Ade receptors, see PTHR24246, and operates directly on adenosine which activates receptor so very direct)
NOTE: allowed all ancient add functions/processes to propagate to ADAL since I verified that all zinc-binding, substrate binding and catalytically important residues annotated in the Swiss-Prot human ADA record are present in ADAL.
PDT, 14 June 2011

# 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).