# HISTORY 18 Jan 2017: Saved by pgaudet using Paint v2.29 on 18 Jan 2017 using PANTHER version 14 Mar 2016: Updated by: TOUCHUP-v1.14 24 Mar 2016: Updated by: TOUCHUP-v1.15 # molecular_function 20150611: Bacteria _PTN000154760 has function aspartate ammonia-lyase activity (GO:0008797) 20150611: node_PTN000154674 has function argininosuccinate lyase activity (GO:0004056) 20150611: node_PTN000154581 has function (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate AMP-lyase (fumarate-forming) activity (GO:0070626) 20150611: node_PTN000154581 has function N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity (GO:0004018) 20170118: node_PTN000154499 has function fumarate hydratase activity (GO:0004333) 20170118: Bacteria _PTN000154760 has LOST/MODIFIED function fumarate hydratase activity (GO:0004333) # cellular_component 20150611: Bacteria _PTN000154760 is found in cytosol (GO:0005829) 20150611: Eukaryota_PTN000154501 is found in mitochondrion (GO:0005739) 20150611: node_PTN000154674 is found in cytosol (GO:0005829) 20170118: root_PTN000154498 is found in cytoplasm (GO:0005737) 20170118: Gammaproteobacteria_PTN000154671 is found in cytosol (GO:0005829) # biological_process 20150611: node_PTN000154499 participates in tricarboxylic acid cycle (GO:0006099) 20150611: node_PTN000154499 participates in fumarate metabolic process (GO:0006106) 20150611: node_PTN000154499 participates in malate metabolic process (GO:0006108) 20150611: Bacteria _PTN000154760 participates in aspartate metabolic process (GO:0006531) 20150611: Bacteria _PTN000154760 participates in cellular amino acid biosynthetic process (GO:0008652) 20150611: node_PTN000154674 participates in arginine biosynthetic process (GO:0006526) 20150611: Mammalia_PTN000154688 participates in urea cycle (GO:0000050) 20150611: node_PTN000154581 participates in purine nucleotide metabolic process (GO:0006163) 20150611: Bacteria _PTN000154760 does NOT participate in tricarboxylic acid cycle (GO:0006099) 20150611: Bacteria _PTN000154760 does NOT participate in fumarate metabolic process (GO:0006106) 20150611: Bacteria _PTN000154760 does NOT participate in malate metabolic process (GO:0006108) 20170118: node_PTN000154674 participates in arginine biosynthetic process via ornithine (GO:0042450) 20170118: node_PTN000154581 participates in purine nucleotide biosynthetic process (GO:0006164) 20170118: node_PTN000154581 participates in 'de novo' AMP biosynthetic process (GO:0044208) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES good review of mechanism of the whole superfamily: pmid:22551392 - fumarase II, adenylosuccinate lyase, argininosuccinate lyase, delta-crystallin, 3-Carboxy-cis,cis-muconate lactonizing enzymes (CMLEs) - "ADL converts 5-aminoimidazole(N-succinylocarboxamide) ribotide (SAICAR) into 5-aminoimidazole-4-carboxamide ribotide (AICAR) and fumarate. In the second reaction, ADL converts adenylosuccinate (ADS) into adenosine monophosphate (AMP) and fumarate" - they share common fold, all tetrameric enzymes - 3 conserved regions (ecFumC): * 137-147 (N141 - but this residue is not conserved in Adenylosuccinate lyases) * 185-195 (T187) * 317-331 (N326 for binding; K324 for catalysis, loop closing; S318 catalytic base)- SS loop * importance of S318 was confirmed by mutagenesis as well, in other species as well * H188 may be the general acid (with a relay system including E331), but it is not conserved in some of the aspirates and apparently the CMLEs * "these enzymes use a common catalytic strategy to process different succinyl-containing substrates. This strategy employs a common binding mode for the succinyl moiety of the substrate, uses general base-catalyzed formation of an enzyme-stabilized aci-carboxylate intermediate, and involves the participation of a highly flexible loop in substrate recruitment and catalysis. Remarkably, a serine residue, which is part of this flexible loop, acts as the catalytic base. The question remains, though, how this strictly conserved serine is activated to function as the catalytic base. An active site histidine is thought to act as the catalytic acid. However, the incomplete conservation of this residue and its dispensable role in some members of the superfamily suggest that the mechanism of elimination of the C? functional group of the substrate may be different for distinct members of the superfamily.? based on the above: - IscW_ISCW009296 is clearly not conserved - doesn?t show any homology - IscW_ISCW009296 and OJ1111_B11.22 are also clearly non-functional JD Reviewed PG 2017-01-08 # 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).