# 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 20140729: node_PTN000472945 has function uroporphyrin-III C-methyltransferase activity (GO:0004851) 20140729: node_PTN000472797 has function uroporphyrinogen decarboxylase activity (GO:0004853) 20140729: node_PTN000472667 has function methylenetetrahydrofolate reductase (NAD(P)H) activity (GO:0004489) 20140729: node_PTN000473081 has function S-adenosylmethionine-homocysteine S-methyltransferase activity (GO:0008898) 20140729: Eumetazoa_PTN001078759 has function betaine-homocysteine S-methyltransferase activity (GO:0047150) 20140729: node_PTN001464934 has function methionine synthase activity (GO:0008705) # cellular_component 20140729: node_PTN000472797 is found in cytosol (GO:0005829) 20140729: node_PTN000472667 is found in cytosol (GO:0005829) 20140729: node_PTN000473081 is found in cytosol (GO:0005829) 20140729: node_PTN001464934 is found in cytosol (GO:0005829) # biological_process 20140729: node_PTN000472945 participates in siroheme biosynthetic process (GO:0019354) 20140729: Bacteria _PTN000473043 participates in enzyme-directed rRNA 2'-O-methylation (GO:0000453) 20140729: node_PTN000472797 participates in heme biosynthetic process (GO:0006783) 20140729: Gammaproteobacteria_PTN000472942 participates in protoporphyrinogen IX biosynthetic process from glutamate (GO:0019353) 20140729: node_PTN000472667 participates in one-carbon metabolic process (GO:0006730) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES Many different clades, will treat each one separately: MTHFR MF: propagate enzymatic function only as others are part of this function; one divergent bacterial subclade with neofunctionalization after duplication CC: propagate only cytosol, as other annotations are high-throughput so not good evidence BP: propagated only one-carbon metabolism, as this is the most precise; technically this reaction is upstream of the SAM cycle and so is upstream of SAM and methionine biosynthesis steps; divergent bacterial subclade with neofunctionalization-- propagated only most precise term mmuM/BHMT clade MF: same reaction (methyltransferase) but different substrate specificities. SAM ancestrally, with duplication resulting in animal BHMT (betaine specificity, note outlier plant sequence that is clearly a misplaced fragment that will disappear with the new trees), and further duplication to get BHMT2 with SMM specificity. Can't annotate loss of ancestral SAM or betaine specificity, as there is of course residual activity that was experimentally noted in PMID 18230605, and annotated, which I have now challenged. CC: only propagated cytosol as only low-throughput experiment was for rat BHMT BP: only propagated SAM cycle, as all of these feed directly into this cycle as methyl donors; all other processes are covered by this one rmsl clade MF: propagated only to bacterial clade following duplication archaeal and eukaryotic members have no EXP annotations and have a range of annotations from SwissProt, so do not assume a more ancient ancestor for this MF did not propagate BP because it is same as MF hemE clade note that E. coli protein of same name appears in MTHFR clade, could be an error MF: propagated to root due to clear conservation outside of EXP annotated range CC: propagated only cytosol because other annotations are HT BP: propagated heme biosynth as other processes are covered by this and MF MET1/cysG clade N-terminal domain is not shared among all members MF: EcoCyc states that the C-terminal domain is responsible for only one function, and this is consistent with EXP annotations in other homologs, so that is the only one propagated CC: all EXPs are HT BP: propagate direct process (cofactor biosynthesis), do not propagate methionine biosynthesis as this is indirect phenotype, siroheme is a cofactor for sulfite reductase which itself is required for Met biosynthesis MET8 clade MF, BP: propagate only as far as duplication in euk/archae ancestor, as domain structures vary in other members of clade this appears to be the protein that is fused with a MET1 like domain in E. coli cysG and several other bacterial genes BP: do not propagate sulfur assimilation as this is a cofactor biosynthesis metH/MTR clade MF: do not propagate SAM methyltransferase activity as this is part of met synthase activity BP: no propagations as need annotation to SAM cycle and others are covered by MF # 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).