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

# molecular_function
20150515: node_PTN000597373 has function acetylglutamate kinase activity (GO:0003991) 
20150515: node_PTN000597373 has function arginine binding (GO:0034618) 
20150515: Eukaryota_PTN000597386 has function acetyl-CoA:L-glutamate N-acetyltransferase activity (GO:0004042) 
20150515: Eukaryota_PTN000597386 has LOST/MODIFIED function acetylglutamate kinase activity (GO:0003991) 

# cellular_component

# biological_process
20150515: node_PTN000597373 participates in arginine biosynthetic process (GO:0006526) 
20150515: Mammalia_PTN001516023 participates in glutamate metabolic process (GO:0006536) 

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

# NOTES
the 2 proteins have very different functions, but they show clear homology
ARG5,6 has 2 functions:
N-acetyl-L-glutamate kinase (NAGK) (1aa-520aa)
N-acetyl-gamma-glutamyl-phosphate reductase (NAGSA) (530aa-)
ARG2: glutamate N-acetyltransferase
pmid: 22529931 (yeast NAGK structure)
ARG2 and ARG5,6 form a complex (metabolon)
the complex is in the mitochondria
2 ARG5,6 dimers associate to form the active enzyme
"all the residues considered important for ATP binding and for catalysis are conserved as, for example, glycines 106, 137, 274 and 305, catalytic lysines 103 and 309, and the intervening aspartate 251, which correspond to EcNAGK glycines 11, 45, 184 and 213, lysines 8 and 217, and aspartate 162, respectively"
alignment:
unikonts apparently gained an additional domain, DUF619 - the ancestral nodes don?t have this domain
the NAGSA function is present only in node PTN000597375 (apparently in unikonts, there was a duplication with one copy gaining extra sequence for this functionality); the other node without this functionality is PTN000597386
in plants and cyanobacteria, the ancestral version of the enzyme (without DUF619 and NAGSA) is present in chloroplasts - PTN001516035
PTN000597386 doesn?t have G106, G137, G305, catalytic K309, D274 (only sporadic), so clearly, it has a different function
pmid:23894642 (human NAGS structure):
"In bacteria NAGS is feedback inhibited by L-arginine. Conversely, in mammals, L-arginine enhances the NAGS activity?
"In microorganisms and plants, NAG is further converted to NAG phosphate by NAG kinase to continue the L-arginine biosynthetic pathway. However, in mammals, NAG has an entirely different role as the essential cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle"
"N-terminal amino acid kinase (AAK) domain and a C-terminal N-acetyltransferase (NAT) domain huNAT: 377aa?534aa? (this is the same as DUF619 above)
"The AAK domain has a structure similar to NAGKs, but it is devoid of NAGK activity. It also has an L-arginine binding site similar to NAGK structures?
active site and NAG binding residues "are either invariant (Phe399, Leu442, Asp443, Lys444, Phe445, Arg474, Arg476, Asn479, Trp498) or conservatively substituted (Lys401 and Phe525) in vertebrate-like NAGS. However, in contrast to bacterial-like NAGS such as Neisseria gonorrhoeae NAGS [5], hNAGS uses different residues to bind NAG, supporting the hypothesis
that the NAT domains of vertebrate-like and bacterial- like NAGS evolved from different ancestors.?
The above residues in huNAGS are well conserved in PTN000597386, so maybe the whole clade can have the same activity

# 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).