# HISTORY
07 May 2016: Updated by: TOUCHUP-v1.18
16 Mar 2016: Updated by: TOUCHUP-v1.14
26 Mar 2016: Updated by: TOUCHUP-v1.15

# molecular_function
20121213: Eukaryota_PTN000454116 has function [methionine synthase] reductase activity (GO:0030586) 
20121213: Opisthokonta_PTN000453822 has function NADPH-hemoprotein reductase activity (GO:0003958) 
20121213: Eumetazoa_PTN001066032 has function nitric-oxide synthase activity (GO:0004517) 

# cellular_component

# biological_process
20121213: Eumetazoa_PTN001066032 participates in nitric oxide mediated signal transduction (GO:0007263) 
20121213: Eumetazoa_PTN001066032 participates in positive regulation of guanylate cyclase activity (GO:0031284) 
20121213: Deuterostomia_PTN000453988 participates in positive regulation of vasodilation (GO:0045909) 
20121213: Deuterostomia_PTN000453988 participates in negative regulation of blood pressure (GO:0045776) 
20121213: Euteleostomi_PTN000453991 participates in inflammatory response (GO:0006954) 
20121213: Euteleostomi_PTN000453991 participates in defense response to bacterium (GO:0042742) 

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

# NOTES
MF
- Propagate NO synthase activity to PTN000453987 (parent of NOS1, NOS2, NOS3)
- Propagate "oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH as one donor, and incorporation of one atom of oxygen" to the root
- Propagate "NADPH-hemoprotein reductase activity" to the root, since most clades have the activity. Used NOT for PTN000454116 (MTRR clade) since this family uses cobalamin rather than a heme as an acceptor.
- Propagate "[methionine synthase] reductase activity" to PTN000454116 (MTRR clade)
- Sulfite reductase activity (Sp Sir1): not enough information to propagate.
CC
- Propagate cytoplasm to PTHR000453764, as some baterial proteins may be in the periplasmic space
BP
- PTN0001066032 (parent of NOS1, NOS2, NOS3): nitric oxide signaling, positive regulation of GC activity
- PTN000453988 (NOS1, NOS2, NOS3 clade - restricted to Deuterostomia): propagate regulation of blood pressure
- NOS1: muscle contraction (mammalia)
- NOS2: defense response to bacteria
inflmmatory response
Ontology question:
peptidyl-cysteine S-nitrosylation - is a spontaneous reaction ? anyhow - the NOS does not directly transfer the NO group ?
Annotation ssues:
Disagree with annotation to 'cAMP-dependent protein kinase regulator activity' (F1LSH9 - RGD)
Human MTRR needs to be annotated to NADPH-hemoprotein reductase activity (see PMID: 10625700). This will allow to annotate PTN000453911.
NOS2: disagree with arginine catabolic process - it's a substrate
NCPR rat: disagree with carnitine metabolic process& most other 'response to' annotations
NOS2 mouse, F1LSH9 rat, others: cellular response to LPS should be TLR4 signaling ?
- PTN000454116 (MTRR clade): Human methionine synthase reductase (MSR) is a 78 kDa flavoprotein that regenerates the active form of cobalamin-dependent methionine synthase  (PMID:17892308) - therefore: should it be annotated to methionine metabolism ?

# 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).