[{"class":"Secondary Metabolism","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Mycosporines (mycosporine-like amino acids [MAAs]) are a diverse family of UV-absorbing secondary\r\nmetabolites that serve as screens against high doses of UV radiation (UVR).  They are found in cyanobacteria, some eukaryotic algae, corals, and fungi. MAAs are water soluble and colorless\r\nand share a 5-dihydroxy, 5-hydroxymethyl, cyclohex-1, 2-ene ring, with a methoxy group at C-2. This core structure is substituted in C-3 with an amino compound (usually an amino acid or amino alcohol) to form oxomycosporines. Ketone replacement with a second amino compound defines the iminomycosporine group. MAAs present typical UV absorption spectra with a single, narrow, and strongly absorbing band that has a maximum around 310 nm for oxomycosporines and around 330 nm for simple iminomycosporines. These compounds\r\nprotect the cell by absorbing UVR and dissipating the energy as heat without generating reactive oxygen species. MAAs have found pharmaceutical and cosmetic applications for their ability to protect skin from UV-mediated damage. \r\nMAA biosynthesis starts from sedoheptulose-7-phosphate (SHP) in the Calvin-Benson-Bassham cycle that is processed by demethyl 4-deoxygadusol (DDG) synthase and O-methyltransferase (O-MT), respectively, to form 4-deoxygadusol (4-DG), the core structure of mycosporines, followed by addition of glycine to 4-DG to form mycosporine-glycine and further condensation of serine to yield shinorine.\r\n \r\n","id":"00c2c133-a6a9-47d1-99c1-b6a451b65fd0","subsystem_id":"Mycosporine_synthesis_cluster","subsystem_name":"Mycosporine synthesis cluster","superclass":"Metabolism","role_name":["Demethyl 4-deoxygadusol synthase MysA","O-methyltransferase MysB","ATP-grasp ligase forming mycosporine-glycine, MysC","Predicted sodium/serine symporter MysT","D-alanine--D-alanine ligase (EC 6.3.2.4) MysD","Mycosporine-producing nonribosomal peptide synthetase"],"notes":["MycA = NpR5600 in N. punctiforme and its homologue Ava_3858 in Anabaena variabilis, encode demethyl 4-deoxygadusol (DDG) synthase, a sugar phosphate cyclase which acts on sedoheptulose 7-phosphate as a substrate. \r\nMycB = NpR5599 and its homologue Ava_3857 code for O-methyltransferases that catalyze the methylation of DDG, giving 4-deoxygadusol. \r\nMysC = product of NpR5598 can catalyze the condensation of glycine onto DG to produce mycosporine-glycine. \r\nMysD = NpF5597 belongs to the ATP-dependent carboxylate-amine-thiol ligase superfamily (ATP-grasp ligases). It most likely  phosphorylates mycosporine-glycine, as a means of activation to allow the addition of the L-serine to the activated cyclohexone core, with the concurrent formation of water, ADP, and Pi. This has to be regarded as a working hypothesis.\r\n\r\nMycT = co-ocures with MycABC and is predicted in this SS to be a sodium/serine symporter.\r\n\r\nWhile functionally analogous, Ava_3855 and NpF5597 are entirely distinct proteins in sequence, functional domain, and, likely, also in mechanism. The reaction catalyzed by Ava_3855 involves the activation of the serine carboxylate, adenylation, and loading by the adenylation domain, which activates the amino acid as aminoacyl-AMP. Subsequently, the activated amino acid is transferred to the 4-phosphopantetheine moiety of the thiolation domain (T-domain) or peptidyl carrier protein (PCP) domain with the release of AMP. Ava_3855 thus functionally belongs together with many nonribosomal\r\npeptide synthetases (NRPSs).\r\n"],"role_id":["Demethyl 4-deoxygadusol synthase MysA","O-methyltransferase MysB","ATP-grasp ligase forming mycosporine-glycine, MysC","Predicted sodium/serine symporter MysT","D-alanine--D-alanine ligase (EC 6.3.2.4) MysD","Mycosporine-producing nonribosomal peptide synthetase"],"pmid":["21963801","21890703"],"_version_":1809284005070110700},{"class":"Energy and Precursor Metabolites Generation","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Methane monooxygenase (MMO),takes a chemically inert hydrocarbon, methane, and converts it to a more active species, methanol. This is a classic monooxygenase reaction in which two reducing equivalents from NAD(P)H are utilized to split the O-O bond of O2. One atom is reduced to water by a 2 e- reduction and the second is incorporated into the substrate to yield methanol\r\n\r\nCH4 + O2 + NAD(P)H + H+ -> CH3OH + NAD(P)+ + H2O\r\nMMOs from different organisms can be of broad specificity and also hydroxylate cyclic alkanes and aromatic compounds.\r\n\r\nThere are two well-studied forms of MMO: the soluble form (sMMO) and the membrane-bound particulate form (pMMO). The active site in sMMO contains a di-iron center bridged by an oxygen atom (Fe-O-Fe), whereas the active site in pMMO utilizes copper, although some propose that pMMO also uses iron.\r\nThe soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath) is a multicomponent enzyme system required for the conversion of methane to methanol. It comprises a hydroxylase, a regulatory protein, and a reductase. The reductase contains two domains: an NADH-binding and FAD-containing flavin domain and a ferredoxin (Fd) domain carrying a [2Fe-2S] cofactor.\r\nIt was isolated from Methylococcus capsulatus (Bath) under methane stress conditions and high copper levels in the growth medium.\r\n","id":"022f782c-f34f-48b5-a79c-7b519fb0d501","subclass":"Central Metabolism","subsystem_id":"Particulate_methane_monooxygenase_(pMMO)","subsystem_name":"Particulate methane monooxygenase (pMMO)","superclass":"Energy","role_name":["Particulate methane monooxygenase A-subunit (EC 1.14.13.25)","Particulate methane monooxygenase B-subunit (EC 1.14.13.25)","Particulate methane monooxygenase C-subunit (EC 1.14.13.25)"],"notes":["\n"],"role_id":["Particulate methane monooxygenase A-subunit (EC 1.14.13.25)","Particulate methane monooxygenase B-subunit (EC 1.14.13.25)","Particulate methane monooxygenase C-subunit (EC 1.14.13.25)"],"pmid":["9525893"],"_version_":1809284005103665200},{"class":"RNA Processing","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"02d0333e-b658-435a-8493-6cd129d5d89c","subclass":"RNA processing and modification","subsystem_id":"N6-(dimethylallyl)adenosine","subsystem_name":"N6-(dimethylallyl)adenosine","superclass":"RNA Processing","role_name":["tRNA dimethylallyltransferase (EC 2.5.1.75)","tRNA-i(6)A37 methylthiotransferase (EC 2.8.4.3)","tRNA-(ms[2]io[6]A)-hydroxylase"],"notes":["\n"],"role_id":["tRNA dimethylallyltransferase (EC 2.5.1.75)","tRNA-i(6)A37 methylthiotransferase (EC 2.8.4.3)","tRNA-(ms[2]io[6]A)-hydroxylase"],"_version_":1809284005104713700},{"class":"Stress Response, Defense and Virulence","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"033f3f8a-6f58-496e-9d7a-07b1f4d08491","subclass":"Stress Response","subsystem_id":"Stress_response_and_cell_wall_lysis_cluster","subsystem_name":"Stress response and cell wall lysis cluster","superclass":"Stress Response, Defense, Virulence","role_name":["FIG016425: Soluble lytic murein transglycosylase and related regulatory proteins (some contain LysM/invasin domains)","FIG001385: N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28)","DnaJ-like protein DjlA","FIG00450637: Antifreeze protein, type I","Lyzozyme M1 (1,4-beta-N-acetylmuramidase) (EC 3.2.1.17)","FIG004335: Membrane-bound lytic murein transglycosylase B precursor (EC 3.2.1.-)","FIG040954: Transporter"],"notes":["\n"],"role_id":["FIG016425: Soluble lytic murein transglycosylase and related regulatory proteins (some contain LysM/invasin domains)","FIG001385: N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28)","DnaJ-like protein DjlA","FIG00450637: Antifreeze protein, type I","Lyzozyme M1 (1,4-beta-N-acetylmuramidase) (EC 3.2.1.17)","FIG004335: Membrane-bound lytic murein transglycosylase B precursor (EC 3.2.1.-)","FIG040954: Transporter"],"_version_":1809284005105762300},{"class":"Nucleosides and Nucleotides","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"03776d58-3cf7-496c-8bb2-a4dea5f2789d","subclass":"Purines","subsystem_id":"GMP_synthase","subsystem_name":"GMP synthase","superclass":"Metabolism","role_name":["GMP synthase [glutamine-hydrolyzing], ATP pyrophosphatase subunit (EC 6.3.5.2)","GMP synthase [glutamine-hydrolyzing], amidotransferase subunit (EC 6.3.5.2)","GMP synthase [glutamine-hydrolyzing] (EC 6.3.5.2)","Glutamine amidotransferase, class I","GMP synthase (EC 6.3.5.2)"],"notes":["\n"],"role_id":["GMP synthase [glutamine-hydrolyzing], ATP pyrophosphatase subunit (EC 6.3.5.2)","GMP synthase [glutamine-hydrolyzing], amidotransferase subunit (EC 6.3.5.2)","GMP synthase [glutamine-hydrolyzing] (EC 6.3.5.2)","Glutamine amidotransferase, class I","GMP synthase (EC 6.3.5.2)"],"_version_":1809284005106811000},{"class":"Carbohydrates","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Subsystem still under construction. It has been created by Andreas Weber, whose exquisite contribution we gratefully acknowledge; it is currently being curated by SvetaG.\r\n\r\nPhotorespiration (oxidative photosynthetic C2 cycle) is a salvage pathway for 2-phosphoglycolate (2-PG), the product of the oxygenase activity of ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), to the Calvin cycle intermediate phosphoglycerate. Photorespiration is a light-dependent process reminiscent of mitochondrial respiration regarding its gas exchange, because O2 is taken up and CO2 released (reviewed in Reumann and Weber, 2006).\r\n\r\nIn plants this pathway is highly compartmentalized and involves reactions in chloroplasts, peroxisomes, and mitochondria (see diagram). The H2O2-producing enzyme glycolate oxidase, catalase, and several aminotransferases of the photorespiratory cycle are located in peroxisomes, with catalase representing the major constituent of the peroxisomal matrix in photosynthetic tissues.  Identification of all the enzymes involved in this process has recently been completed, but very little is known still about the metabolite transporters for the exchange of photorespiratory intermediates between the organelles involved, and about the regulation of this pathway (Reumann and Weber, 2006).  In brief, the photorespiratory reactions first continue in the chloroplast stroma by dephosphorylation of 2-PG catalyzed by phosphoglycolate phosphatase (PGP).  Glycolate diffuses into the matrix of peroxisomes, where it is oxidized to glyoxylate by glycolate  oxidase (GOX) concomitant with the production of hydrogen peroxide (H2O2).  Glyoxylate is  transaminated by two aminotransferases, Ser:glyoxylate and Glu:glyoxylate aminotransferase (SGT and GGT), which ideally cooperate at a 1:1 stoichiometry.  The resulting Gly is the substrate of two mitochondrial  enzymes: Glycine decarboxylase (GDC) decomposes the  amino acid to CO2, NH3, and NADH and transfers a C1 unit  to 5,10-methylene tetrahydrofolate (THF). Serine hydroxymethyl transferase (SHMT) attaches this methylene unit to the  second Gly molecule to produce Ser. Serine diffuses back to leaf  peroxisomes, where the amino group is removed by SGT to  yield hydroxypyruvate, which is reduced by NADH provided  by peroxisomal malate dehydrogenase (pMDH) to form  glycerate.  Stromal glycerate kinase (GLYK) catalyzes the  final phosphorylation step of the photorespiratory cycle to  produce the Calvin cycle intermediate 3-PGA (from Reumann and Weber, 2006). \r\n\r\nAUXILIARY ROLES:  Gln synthase and Fd-dependent Glu synthase (GOGAT) are included in this SS due to their function in re-assimilation of photorespiratory ammonia generated by Glycine decarboxylase;  pMDH provides reducing equivalents, imported into leaf peroxisomes in the form of malate.\r\n\r\nIn cyanobacteria photorespiratory 2-phosphoglycolate metabolism is not yet clear, but it appears that in these organisms phosphoglycolate is metabolized by the cooperative action of plant-like C2 cycle and the bacterial-type glycerate pathway (Eisenhut et al., 2006).  SS under construction\r\n","id":"04c8a2b6-96aa-40c1-b256-758a01ec853b","subclass":"CO2 fixation","subsystem_id":"Photorespiration_(oxidative_C2_cycle)","subsystem_name":"Photorespiration (oxidative C2 cycle)","superclass":"Metabolism","role_name":["2-hydroxy-3-oxopropionate reductase (EC 1.1.1.60)","2-oxoglutarate/malate translocator","Aminomethyltransferase (glycine cleavage system T protein) (EC 2.1.2.10)","Catalase (EC 1.11.1.6)","D-Lactate dehydrogenase, cytochrome c-dependent (EC 1.1.2.4)","D-glycerate 3-kinase (EC 2.7.1.31), plant type","Dihydrolipoamide dehydrogenase (EC 1.8.1.4)","Expressed protein possibly involved in photorespiration","Glycerate kinase (EC 2.7.1.31)","Glycine cleavage system H protein","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P protein) (EC 1.4.4.2)","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P1 protein) (EC 1.4.4.2)","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P2 protein) (EC 1.4.4.2)","Glycolate dehydrogenase (EC 1.1.99.14), FAD-binding subunit GlcE","Glycolate dehydrogenase (EC 1.1.99.14), iron-sulfur subunit GlcF","Glycolate dehydrogenase (EC 1.1.99.14), subunit GlcD","Glycolate oxidase (EC 1.1.3.15)","Glycolate permease","Glyoxylate carboligase (EC 4.1.1.47)","Hydroxypyruvate reductase (EC 1.1.1.81)","L-alanine:glyoxylate aminotransferase (EC 2.6.1.44)","Malate synthase (EC 2.3.3.9)","Malate synthase G (EC 2.3.3.9)","Malyl-CoA lyase (EC 4.1.3.24)","Phosphoglycolate phosphatase (EC 3.1.3.18)","Ribulose bisphosphate carboxylase (EC 4.1.1.39)","Ribulose bisphosphate carboxylase large chain (EC 4.1.1.39)","Ribulose bisphosphate carboxylase small chain (EC 4.1.1.39)","Ribulose-1,5-bisphosphate carboxylase, Type III (EC 4.1.1.39)","Serine hydroxymethyltransferase (EC 2.1.2.1)","Serine--glyoxylate aminotransferase (EC 2.6.1.45)"],"notes":["References\r\n\r\n1. S. Reumann, Andreas P.M. Weber.  2006.  Plant peroxisomes respire in the light: Some gaps of the photorespiratory C2 cycle have become filled�Others remain. Biochimica et Biophysica Acta 1763 (2006) 1496 � 1510\r\n2. Eisenhut et al., M. Hagemann.  2006. The Plant-Like C2 Glycolate Cycle and the Bacterial-Like Glycerate Pathway Cooperate in Phosphoglycolate Metabolism in Cyanobacteria. Plant Physiology, 142:333�342\r\n3. Boldt R,   Edner C,   Kolukisaoglu U,   Hagemann M,   Weckwerth W,   Wienkoop S,   Morgenthal K,   Bauwe H.  2005.  D-glycerate 3-kinase, the last unknown enzyme in the photorespiratory cycle in Arabidopsis, belongs to a novel kinase family. Plant Cell, 17(8):2413-20. \r\n4. Igarashi D,  Miwa T,  Seki M,  Kobayashi M,  Kato T,  Tabata S,  Shinozaki K,  Ohsumi C.   2003.  Identification of photorespiratory glutamate:glyoxylate aminotransferase (GGAT) gene in Arabidopsis. Plant J, 33(6):975-87.\r\n5. Voll LM, Jamai A, Renne P, Voll H, McClung CR, Weber AP. 2006. The photorespiratory Arabidopsis shm1 mutant is deficient in SHM1. Plant Physiol, 140(1):59-66\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n"],"role_id":["2-hydroxy-3-oxopropionate reductase (EC 1.1.1.60)","2-oxoglutarate/malate translocator","Aminomethyltransferase (glycine cleavage system T protein) (EC 2.1.2.10)","Catalase (EC 1.11.1.6)","D-Lactate dehydrogenase, cytochrome c-dependent (EC 1.1.2.4)","D-glycerate 3-kinase (EC 2.7.1.31), plant type","Dihydrolipoamide dehydrogenase (EC 1.8.1.4)","Expressed protein possibly involved in photorespiration","Glycerate kinase (EC 2.7.1.31)","Glycine cleavage system H protein","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P protein) (EC 1.4.4.2)","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P1 protein) (EC 1.4.4.2)","Glycine dehydrogenase [decarboxylating] (glycine cleavage system P2 protein) (EC 1.4.4.2)","Glycolate dehydrogenase (EC 1.1.99.14), FAD-binding subunit GlcE","Glycolate dehydrogenase (EC 1.1.99.14), iron-sulfur subunit GlcF","Glycolate dehydrogenase (EC 1.1.99.14), subunit GlcD","Glycolate oxidase (EC 1.1.3.15)","Glycolate permease","Glyoxylate carboligase (EC 4.1.1.47)","Hydroxypyruvate reductase (EC 1.1.1.81)","L-alanine:glyoxylate aminotransferase (EC 2.6.1.44)","Malate synthase (EC 2.3.3.9)","Malate synthase G (EC 2.3.3.9)","Malyl-CoA lyase (EC 4.1.3.24)","Phosphoglycolate phosphatase (EC 3.1.3.18)","Ribulose bisphosphate carboxylase (EC 4.1.1.39)","Ribulose bisphosphate carboxylase large chain (EC 4.1.1.39)","Ribulose bisphosphate carboxylase small chain (EC 4.1.1.39)","Ribulose-1,5-bisphosphate carboxylase, Type III (EC 4.1.1.39)","Serine hydroxymethyltransferase (EC 2.1.2.1)","Serine--glyoxylate aminotransferase (EC 2.6.1.45)"],"_version_":1809284005107859500},{"class":"Amino Acids and Derivatives","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"067a2ff0-30f8-404f-95e7-868f1aeab42b","subclass":"Lysine, threonine, methionine, and cysteine","subsystem_id":"S-methylmethionine","subsystem_name":"S-methylmethionine","superclass":"Metabolism","role_name":["Homocysteine S-methyltransferase (EC 2.1.1.10)","S-methylmethionine permease"],"notes":["\n"],"role_id":["Homocysteine S-methyltransferase (EC 2.1.1.10)","S-methylmethionine permease"],"_version_":1809284005113102300},{"class":"Clustering-based subsystems","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"00111f89-eb07-4bdf-bebf-d3d832c55ea1","subclass":"Cell Division","subsystem_id":"Cell_division_related_cluster","subsystem_name":"Cell division related cluster","role_name":["Chromosome (plasmid) partitioning protein ParA","Chromosome (plasmid) partitioning protein ParB","FIG00649665: hypothetical protein","Signal peptidase I (EC 3.4.21.89)","FIG00496209: hypothetical protein","4-hydroxy-tetrahydrodipicolinate reductase (EC 1.17.1.8)"],"notes":["\n"],"role_id":["Chromosome (plasmid) partitioning protein ParA","Chromosome (plasmid) partitioning protein ParB","FIG00649665: hypothetical protein","Signal peptidase I (EC 3.4.21.89)","FIG00496209: hypothetical protein","4-hydroxy-tetrahydrodipicolinate reductase (EC 1.17.1.8)"],"_version_":1809284005113102300},{"class":"Secondary Metabolism","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0095a728-1c9e-4789-bbf8-72e3eeb67653","subclass":"Metabolism of Aromatic Compounds","subsystem_id":"Vanillate_and_syringate_utilization","subsystem_name":"Vanillate and syringate utilization","superclass":"Metabolism","role_name":["Transcriptional regulator LigR, LysR family","Protocatechuate 4,5-dioxygenase alpha chain (EC 1.13.11.8)","Protocatechuate 4,5-dioxygenase beta chain (EC 1.13.11.8)","4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase","2-pyrone-4,6-dicarboxylic acid hydrolase (EC 3.1.1.57)","4-oxalomesaconate hydratase (EC 4.2.1.83)","4-carboxy-4-hydroxy-2-oxoadipate aldolase (EC 4.1.3.17)","Oxaloacetate decarboxylase (EC 4.1.1.3)"],"notes":["\n"],"role_id":["Transcriptional regulator LigR, LysR family","Protocatechuate 4,5-dioxygenase alpha chain (EC 1.13.11.8)","Protocatechuate 4,5-dioxygenase beta chain (EC 1.13.11.8)","4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase","2-pyrone-4,6-dicarboxylic acid hydrolase (EC 3.1.1.57)","4-oxalomesaconate hydratase (EC 4.2.1.83)","4-carboxy-4-hydroxy-2-oxoadipate aldolase (EC 4.1.3.17)","Oxaloacetate decarboxylase (EC 4.1.1.3)"],"_version_":1809284005114151000},{"class":"Protein Synthesis","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"011ec1bf-f806-4f82-b52b-ec1346204546","subclass":"Aminoacyl-tRNA-synthetases","subsystem_id":"tRNA_aminoacylation,_Phe","subsystem_name":"tRNA aminoacylation, Phe","superclass":"Protein Processing","role_name":["Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20)","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20)","Phenylalanyl-tRNA synthetase (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20), chloroplast","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20), chloroplast","Protein with domain from phenylalanyl-tRNA synthetase alpha chain","Phenylalanyl-tRNA synthetase domain protein (Bsu YtpR)"],"notes":["Phe:\r\nThere is an unfortunate conflict between the use of alpha and beta subunit designations between bacteria and eukaryotes.  subunits in eukaryotes should probably be annotated as small (= bacterial alpha) and large (= bacterial beta) subunits, which avoids the conflict.  Unfortunately, UniProt does not help here.\r\n"],"role_id":["Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20)","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20)","Phenylalanyl-tRNA synthetase (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20), mitochondrial","Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20), chloroplast","Phenylalanyl-tRNA synthetase beta chain (EC 6.1.1.20), chloroplast","Protein with domain from phenylalanyl-tRNA synthetase alpha chain","Phenylalanyl-tRNA synthetase domain protein (Bsu YtpR)"],"_version_":1809284005115199500},{"class":"Cell Envelope, Capsule and Slime layer","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Pseudomonas aeroginosa forms biofilms, which are cellular aggregates encased in an extracellular matrix.  Two loci, pel and psl, have been identified and are involved in the production of carbohydrate-rich components of the biofilm matrix.  The pel gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14.  The psl gene cluster is involved in the production of a mannose-rich matrix material in P. aeruginosa strain ZK2870.  Either carbohydrate-rich matrix appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870.\r\n\r\nThese 12 adjacent genes named psl genes, are involved in the formation of the pellicle's extracellular matrix and are required for the formation of the solid surface-associated biofilms that encase the cells. The psl gene cluster is involved in the production of a mannose-rich matrix material in P. aeruginosa strain ZK2870. These biofilms aid in the survival in a variety of environments.\r\n\r\nReferences:\r\n\r\nFriedman L1, Kolter R. 2004 Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix. J Bacteriol. 2004 Jul;186(14):4457-65. PMID: 15231777 \r\n\r\nFranklin MJ1, Nivens DE, Weadge JT, Howell PL. 2011 Biosynthesis of the Pseudomonas aeruginosa Extracellular Polysaccharides, Alginate, Pel, and Psl. Front Microbiol. 2011 Aug 22;2:167. PMID: 21991261\r\n\r\n","id":"0962aea8-0669-4505-84a8-87e8272f094f","subclass":"Capsule and Slime layer","subsystem_id":"Extracellular_matrix_proteins_(PSL)_involved_in_mannose-rich_biofilm_formation_in_Pseudomonas","subsystem_name":"Extracellular matrix proteins (PSL) involved in mannose-rich biofilm formation in Pseudomonas","superclass":"Cell Envelope","role_name":["Pellicle/biofilm biosynthesis protein PslA, polyprenyl glycosylphosphotransferase","Pellicle/biofilm biosynthesis protein PslC, CAZy glycosyltransferase family 2","Pellicle/biofilm biosynthesis periplasmic/outer membrane lipoprotein PslD, Wza-like","Pellicle/biofilm biosynthesis polysaccharide copolymerase/tyrosine-kinase PslE, Wzc-like","Pellicle/biofilm biosynthesis protein PslF, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis protein PslG, CAZy glycosyltransferase family 39","Pellicle/biofilm biosynthesis protein PslH, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis protein PslI, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis inner membrane protein PslJ, possible O-antigen ligase","Pellicle/biofilm biosynthesis inner membrane protein PslK, MATE transporter family","Pellicle/biofilm biosynthesis inner membrane protein PslL, acetyltransferase"],"notes":["Quoted from PMID:21991261 -\r\n\r\n\"One strategy for bacterial adaptation is to self-encapsulate with matrix material, primarily composed of secreted extracellular polysaccharides. Pseudomonas aeruginosa  has the genetic capacity to produce at least three secreted polysaccharides; alginate, PSL, and PEL. These polysaccharides differ in chemical structure and in their biosynthetic mechanisms. Since alginate is often associated with chronic pulmonary infections, its biosynthetic pathway is the best characterized. However, alginate is only produced by a subset of P. aeruginosa strains. Most environmental and other clinical isolates are non-micoid and use either PEL or PSL as the primary matrix structural polysaccharide.  \r\n\r\nThe PEL gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14.  The PSL gene cluster is involved in the production of a mannose-rich matrix material in P. aeruginosa strain ZK2870.  Either carbohydrate-rich matrix appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870.  Limited information is available on the biosynthesis of these polysaccharides (reviewed in PMID:21991261, PMID:25438014, PMID:22176658).  It was predicted (in PMID:21991261) that alginate and PEL share certain features, while PSL biosynthesis resembles the EPS/CPS capsular biosynthesis pathway of Escherichia coli, where the PSL pentameric subunits are assembled in association with an isoprenoid lipid carrier\"\r\n"],"role_id":["Pellicle/biofilm biosynthesis protein PslA, polyprenyl glycosylphosphotransferase","Pellicle/biofilm biosynthesis protein PslC, CAZy glycosyltransferase family 2","Pellicle/biofilm biosynthesis periplasmic/outer membrane lipoprotein PslD, Wza-like","Pellicle/biofilm biosynthesis polysaccharide copolymerase/tyrosine-kinase PslE, Wzc-like","Pellicle/biofilm biosynthesis protein PslF, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis protein PslG, CAZy glycosyltransferase family 39","Pellicle/biofilm biosynthesis protein PslH, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis protein PslI, CAZy glycosyltransferase family 4","Pellicle/biofilm biosynthesis inner membrane protein PslJ, possible O-antigen ligase","Pellicle/biofilm biosynthesis inner membrane protein PslK, MATE transporter family","Pellicle/biofilm biosynthesis inner membrane protein PslL, acetyltransferase"],"pmid":["15231777","21991261"],"_version_":1809284005116248000},{"class":"Respiration","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0bd01700-816a-473c-b00d-9a9859621501","subclass":"Electron accepting reactions","subsystem_id":"Cytochrome_c_oxidase_EC_1.9.3.1","subsystem_name":"Cytochrome c oxidase EC 1.9.3.1","superclass":"Energy","role_name":["Cytochrome c oxidase (cbb3-type) subunit CcoN (EC 1.9.3.1)","Cytochrome c oxidase (cbb3-type) subunit CcoO (EC 1.9.3.1)","Cytochrome c oxidase (cbb3-type) subunit CcoP (EC 1.9.3.1)","Cytochrome oxidase biogenesis protein Sco1/SenC/PrrC, thiol-disulfide reductase involved in Cu(I) insertion into CoxII Cu(A) center","Cytochrome c oxidase associated membrane protein","Type cbb3 cytochrome oxidase biogenesis protein CcoG, involved in Cu oxidation","Type cbb3 cytochrome oxidase biogenesis protein CcoS, involved in heme b insertion","cytochrome cbb3 oxidase maturation protein CcoH","Cytochrome c oxidase (cbb3-type) subunit CcoQ (EC 1.9.3.1)"],"notes":["\n"],"role_id":["Cytochrome c oxidase (cbb3-type) subunit CcoN (EC 1.9.3.1)","Cytochrome c oxidase (cbb3-type) subunit CcoO (EC 1.9.3.1)","Cytochrome c oxidase (cbb3-type) subunit CcoP (EC 1.9.3.1)","Cytochrome oxidase biogenesis protein Sco1/SenC/PrrC, thiol-disulfide reductase involved in Cu(I) insertion into CoxII Cu(A) center","Cytochrome c oxidase associated membrane protein","Type cbb3 cytochrome oxidase biogenesis protein CcoG, involved in Cu oxidation","Type cbb3 cytochrome oxidase biogenesis protein CcoS, involved in heme b insertion","cytochrome cbb3 oxidase maturation protein CcoH","Cytochrome c oxidase (cbb3-type) subunit CcoQ (EC 1.9.3.1)"],"_version_":1809284005119393800},{"class":"Amino Acids and Derivatives","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"03e0cb72-7461-409d-8e81-9538f3c7aa54","subclass":"Lysine, threonine, methionine, and cysteine","subsystem_id":"Diaminopimelate_Synthesis_","subsystem_name":"Diaminopimelate Synthesis ","superclass":"Metabolism","role_name":["Aspartokinase (EC 2.7.2.4)","Aspartate-semialdehyde dehydrogenase (EC 1.2.1.11)","4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7)","4-hydroxy-tetrahydrodipicolinate reductase (EC 1.17.1.8)","2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (EC 2.3.1.117)","N-succinyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.17)","N-succinyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.17), type 2","N-succinyl-L,L-diaminopimelate desuccinylase (EC 3.5.1.18)","2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase (EC 2.3.1.89)","N-acetyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.-)","N-acetyl-L,L-diaminopimelate deacetylase (EC 3.5.1.47)","L,L-diaminopimelate aminotransferase (EC 2.6.1.83)","L,L-diaminopimelate aminotransferase (EC 2.6.1.83), methanococcal","L,L-diaminopimelate aminotransferase (EC 2.6.1.83), DapL2 type","Diaminopimelate epimerase (EC 5.1.1.7)","Meso-diaminopimelate D-dehydrogenase (EC 1.4.1.16)","Diaminopimelate decarboxylase (EC 4.1.1.20)"],"notes":["\n"],"role_id":["Aspartokinase (EC 2.7.2.4)","Aspartate-semialdehyde dehydrogenase (EC 1.2.1.11)","4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7)","4-hydroxy-tetrahydrodipicolinate reductase (EC 1.17.1.8)","2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (EC 2.3.1.117)","N-succinyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.17)","N-succinyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.17), type 2","N-succinyl-L,L-diaminopimelate desuccinylase (EC 3.5.1.18)","2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase (EC 2.3.1.89)","N-acetyl-L,L-diaminopimelate aminotransferase (EC 2.6.1.-)","N-acetyl-L,L-diaminopimelate deacetylase (EC 3.5.1.47)","L,L-diaminopimelate aminotransferase (EC 2.6.1.83)","L,L-diaminopimelate aminotransferase (EC 2.6.1.83), methanococcal","L,L-diaminopimelate aminotransferase (EC 2.6.1.83), DapL2 type","Diaminopimelate epimerase (EC 5.1.1.7)","Meso-diaminopimelate D-dehydrogenase (EC 1.4.1.16)","Diaminopimelate decarboxylase (EC 4.1.1.20)"],"_version_":1809284005120442400},{"class":"Stress Response, Defense and Virulence","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0406e9c8-0b68-4d25-8671-f55131afee4f","subclass":"Stress Response","subsystem_id":"Sugar-phosphate_stress_regulation","subsystem_name":"Sugar-phosphate stress regulation","superclass":"Stress Response, Defense, Virulence","role_name":["SgrR, sugar-phosphate stress, transcriptional activator of SgrS small RNA","Sugar-phosphate stress protein SgrT (embedded in SgrS)"],"notes":["\r\n"],"role_id":["SgrR, sugar-phosphate stress, transcriptional activator of SgrS small RNA","Sugar-phosphate stress protein SgrT (embedded in SgrS)"],"_version_":1809284005121491000},{"class":"Photosynthesis","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0dd6f099-2fef-465c-82df-60cc1718cf68","subclass":"Electron transport and photophosphorylation","subsystem_id":"Photosystem_I-type_photosynthetic_reaction_center","subsystem_name":"Photosystem I-type photosynthetic reaction center","superclass":"Energy","role_name":["Photosystem P840 reaction center large subunit PscA","Photosystem P840 reaction center iron-sulfur subunit PscB","Photosystem P840 reaction center subunit PscC, cytochrome c-551","Photosystem P840 reaction center subunit PscD"],"notes":["Variant codes:\r\n\r\n 1 = an organisms contains homodimeric PSI-like reaction center\r\n-1 = PSI-like reaction center of this type is not present in an organism\r\n u = an organisms contains homodimeric PSI-like reaction center, but it's genome is currently incomplete\r\n\r\nGreen sulfur bacteria and Heliobacteria contain homodimeric type I reaction centers, utilizing low-potential FeS clusters as electron acceptors. The RC complex consists of four subunits, PscA, PscB, PscC, and PscD  with an antenna size of about 30 bacteriochlorophyll (BChl)  molecules (whereas the heterodimeric photosystem I complex is  composed of 12 polypeptides with a much larger antenna size of  nearly 100 chlorophyll (Chl) molecules.\r\n\r\nHomodimeric type I RCs have not been successful targets for crystal structural analysis and mutagenic approach due to the obligate anaerobic and photoautotrophic nature of green sulfur bacteria and heliobacteria.  RC complexes isolated from them are very fragile when exposed to oxygen, and many RC-related genes are essential.  However, a study on the molecular level of the homodimeric RCs, which have a simple architecture and still retain the features of an ancestral RC, will offer valuable information to understand the mechanism and evolution of photosynthetic apparatuses (Tsukatani et al., 2004). \r\n\r\nReferences:\r\n\r\n1. Y. Tsukatani, R. Miyamoto, S. Itoh, and H. Oh-oka.  2004. Function of a PscD Subunit in a Homodimeric Reaction Center Complex of the Photosynthetic Green Sulfur Bacterium Chlorobium tepidum Studied by Insertional Gene Inactivation. Regulation of energy transfer and ferredoxin-mediated NADP+ reduction on the cytoplasmic side. J. Biol. Chem. 279(49), p.51122�51130 \r\n\r\n2. A. Ben-Shem, F. Frolow, and N. Nelson. 2004.  Evolution of photosystem I � from symmetry through pseudosymmetry to asymmetry.  FEBS Lett., 564(3):274-280\r\n\r\n3. Michael Biittner, Dian-Lin Xie, Hannah Nelson, Wilfried Pinther, Giinter Hauska, and Nathan Nelson.  1992.  The Photosystem I-like P840-reaction center of Green S-bacteria \r\nis a homodimer. Biochimica et Biophysica Acta, I101 (1992) 154-156\r\n\r\n4. Ben-Shem A,  Frolow F, Nelson N. 2004.  Evolution of photosystem I - from symmetry through pseudo-symmetry to asymmetry. FEBS Lett., 564(3):274-80.\r\n\r\n5. Itoh M, Seo D., Sakurai H, Setif P.  2002. Kinetics of electron transfer between soluble cytochrome c-554 and purified reaction center complex from the green sulfur bacterium Chlorobium tepidum. Photosynth Res. 2002;71(1-2):125-35.\r\n\r\n"],"role_id":["Photosystem P840 reaction center large subunit PscA","Photosystem P840 reaction center iron-sulfur subunit PscB","Photosystem P840 reaction center subunit PscC, cytochrome c-551","Photosystem P840 reaction center subunit PscD"],"_version_":1809284005122539500},{"class":"Sulfur Metabolism","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0411fea5-1318-4579-ae57-5ddfdd855d91","subsystem_id":"Sulfate_assimilation_related_cluster","subsystem_name":"Sulfate assimilation related cluster","superclass":"Metabolism","role_name":["Putative alkanesulfonate metabolism utilization regulator","Adenylylsulfate reductase alpha-subunit (EC 1.8.99.2)","Adenylylsulfate reductase beta-subunit (EC 1.8.99.2)","Organosulfonate ABC transporter substrate-binding protein","Organosulfonate ABC transporter permease protein","Organosulfonate ABC transporter ATP-binding protein","HEAT repeat-containing protein","FIG028220: hypothetical protein co-occurring with HEAT repeat protein"],"notes":["\n"],"role_id":["Putative alkanesulfonate metabolism utilization regulator","Adenylylsulfate reductase alpha-subunit (EC 1.8.99.2)","Adenylylsulfate reductase beta-subunit (EC 1.8.99.2)","Organosulfonate ABC transporter substrate-binding protein","Organosulfonate ABC transporter permease protein","Organosulfonate ABC transporter ATP-binding protein","HEAT repeat-containing protein","FIG028220: hypothetical protein co-occurring with HEAT repeat protein"],"_version_":1809284005124636700},{"class":"Regulation and Cell signaling","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0e515733-e17d-48af-8a77-d25b6bfe5f6d","subsystem_id":"Sigma54-dependent_transcription_related_gene_cluster","subsystem_name":"Sigma54-dependent transcription related gene cluster","superclass":"Regulation And Cell Signaling","role_name":["Suppressor of sigma54-dependent transcription, PspA-like","Hypothetical protein co-occurring with PspA-like suppressor"],"notes":["\n"],"role_id":["Suppressor of sigma54-dependent transcription, PspA-like","Hypothetical protein co-occurring with PspA-like suppressor"],"_version_":1809284005125685200},{"class":"Protein Fate (folding, modification, targeting, degradation)","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"0fa4d028-8f81-4afb-8c4b-f9b81d529f8e","subclass":"Protein targeting, sorting, translocation","subsystem_id":"Twin-arginine_translocation_system","subsystem_name":"Twin-arginine translocation system","superclass":"Protein Processing","role_name":["Twin-arginine translocation protein TatA","Twin-arginine translocation protein TatB","Twin-arginine translocation protein TatC","Twin-arginine translocation protein TatE","Twin-arginine translocation protein TatAd","Twin-arginine translocation protein TatCd","Twin-arginine translocation protein TatAy","Twin-arginine translocation protein TatCy"],"notes":["The Twin Arginine Transport system (TAT) is able to export folded proteins.  This is very important for\r\nsome proteins that have cofactors added in the cytoplasm.\r\n\r\nTatA, TatB and TatC are the most common combination of proteins.\r\nTatC defines the specificity of the proteins exported.\r\n\r\nVarient codes:\r\n  +1 for TatA\r\n  +2 for TatB\r\n  +4 for TatC\r\n\r\nThe TatD protein is seem to have no effect on the activity in vivo.\r\nIt has Mg-dependent DNase activity in vitro.\r\nIt is a member of a large famility of DNases.\r\n\"Putative deoxyribonuclease YcfH\" is very widely distributed, and is often clustered with translation associated genes.\r\nIt and other members of the family are collected in the YcfH subsystem.\r\n\r\n\r\n"],"role_id":["Twin-arginine translocation protein TatA","Twin-arginine translocation protein TatB","Twin-arginine translocation protein TatC","Twin-arginine translocation protein TatE","Twin-arginine translocation protein TatAd","Twin-arginine translocation protein TatCd","Twin-arginine translocation protein TatAy","Twin-arginine translocation protein TatCy"],"_version_":1809284005125685200},{"class":"Respiration","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"The cytochrome b-c1 complex of the respirator chain and the b6-f complex of OXYGENIC photosynthesis have long been known (Hauska et al., 1983) to be similar in (a) their redox prosthetic groups, which are present in the same stoichiometry, two b- and one c-type heme, one [2Fe-2S] cluster per unit; (b) use of quinol/semiquinol as electron and proton donor; and (c) their functions:\r\n(i) mediation of electron transfer between the major integral electron donor (dehydrogenases and photosystem II, respectively) an acceptor (cytochrome oxidase and photosystem I)   complexes\r\n(ii) electrogenic charge transfer and H+ translocation (Soriano et al., 1999). \r\n\r\nBut there are several important differences between b-c1 and b6-f (Soriano et al., 1999) as well:\r\n\r\n1. The cyt b (bc1) polypeptide with eight TM helices A-H is replaced in the b6 f complex by two smaller integral polypeptides (cyt b6 and subunit IV) consisting of helices A-D and E-G (Widger et al., 1984).  \r\n\r\n2. Cytochromes f and c1 are completely different in terms of both proteins sequence and structure, except for both being c-type cytochromes with the characteristic Cys-X-Y-Cys-His c-heme binding sequence motif.\r\n\r\n3.  While the four larger subunits of the b6 f complex have structural and/or functional similarity to that of bc1, the 3(4) small subunits are unique to the b6 f complex. \r\n\r\n4. There are one molecule each of chlorophyll a (Huang  et al., 1994) and beta-carotene (Zhang et al., 1999a) present in the b6 f complex (absent in bc1).\r\n\r\n5. Lipid content can be different, as there are 5 molecules per monomer of the unique lipid monogalactosyl-diacylglycerol present in the b6 f complex (Soriano et al., 1999).\r\n\r\nThe bc1 complex in plants is encoded in Subsystem: Respiratory complex III (cytochrome b-c1) in plants. Bacterial bc1 complexes are encodes in SS: Ubiquinone Menaquinone-cytochrome c reductase complexes\r\n\r\n==============================\r\nThis subsystem covers protein complexes involved in a single AraCyc reaction:\r\nplastoquinol�plastocyanin reductase: <a href=\"http://pmn.plantcyc.org/PLANT/NEW-IMAGE?type=REACTION&object=PLASTOQUINOL--PLASTOCYANIN-REDUCTASE-RXN\">PLASTOQUINOL--PLASTOCYANIN-REDUCTASE-RXN</a>\r\n==============================\r\n\r\nReferences:\r\n\r\n1. G.M. Soriano, M.V. Ponamarev, C.J. Carrell, D. Xia, J.L. Smith, and W.A. Cramer. 1999.  Comparison of the Cytochrome bc1 Complex with the Anticipated Structure of the Cytochrome b6 f Complex: De Plus Ca Change de Plus C�est la Meme Chose. Journal of Bioenergetics and Biomembranes, 31(3):201-213\r\n","id":"11260d57-d617-4af9-b478-3ae898bf1737","subclass":"Plastidial (cyanobacterial) electron transport system","subsystem_id":"Cytochrome_b6-f_complex_in_plants_(plastidial)_and_cyanobacteria","subsystem_name":"Cytochrome b6-f complex in plants (plastidial) and cyanobacteria","superclass":"Energy","role_name":["Cytochrome b6-f complex subunit V (PetG)","Cytochrome b6-f complex subunit VI (PetL)","Cytochrome b6-f complex subunit, apocytochrome f","Cytochrome b6-f complex iron-sulfur subunit PetC1 (Rieske iron sulfur protein EC 1.10.9.1)","Cytochrome b6-f complex alternative Rieske iron sulfur protein PetC2","Cytochrome b6-f complex alternative Rieske iron sulfur protein PetC3","Cytochrome b6-f complex subunit, cytochrome b6","Cytochrome b6-f complex subunit, cytochrome b6, putative","Cytochrome b6-f complex subunit IV (PetD)","Cytochrome b6-f complex subunit VII (PetM)","Cytochrome b6-f complex subunit VIII (PetN)"],"notes":["Observations, conjectures:\r\n\r\n1. Missing small subunits -\r\n Cytochrome b6-f complex of cyanobacteria is formed by four main relatively large subnits (PetA, PetB, PetC, and PetD) and several small hydrophobic 3.2-4.2 kDa polypeptides PetG, L, M, and N. In addition to these subunits, plant cyt b6/f complex contains PetH (PMID: 11483610). While orthologs of large conserved subunits are easily identifiable in a genome sequence, the small subunits are often overlooked during ORF calling due to their small size.  Hence, the absence of orthologs of small subunits in a genome does NOT imply nonfunctional cyt b6-f complex.\r\n\r\n2. PetC protein family -\r\nCyanobacteria come in two cytocrome b6-f flavors: some [variant code 1] contain a single Rieske iron sulfur protein (encoded by petC1 always cotranscribed with petA).  Others [variant code 2] contain from 2 to 4 additional Rieske proteins (encoded by genes petC2, petC3, etc., differing from petC1 to various degrees).  So far, association of PetC2 and PetC3 with functional cytocrome b6-f complex has been demonstrated formally only in Synechocystis PCC 6803, and merely inferred in other variant 2 species. \r\n\r\n3. A speculation/prediction:\r\nWhile biological significance of the presence of different Rieske proteins is not clear, I can�t help noting, that ALL �mono-PetC� species identified so far are strict photoautptrophs, while all (but one � see below) �multiple-PetC� species are capable of photoheterotrophic growth (inferior to photoautrophy in a life of a cyanobacterium).  Since cytochrome b6/f complex in cyanobacteria is an essential component of both the respiratory and photosynthetic electron transfer chain, can it be that substitution of the default �photoautotrophic� PetC1 Rieske protein for a different one in the cyt b6/f complex is a necessary requirement for activation of (photo)heterotrophic growth based solely on respiratory electron chain?  \r\n\r\nNostoc (Anabaena) sp. PCC 7120 � the only exception of this observation � is an interesting case in itself.  Comparative genomic analysis of central carbon metabolism in cyanobacteria (conducted earlier by Dr. Ivanova et al.) has detected consistent differences between obligate and facultative photoautotrophs in organization of glycolysis and TCA. Interestingly, Nostoc sp. PCC 7120 was an exception in that study as well: it was the only photoautotrophic cyanobacterium with �photoheterotrophic� type of its central carbon metabolism.  \r\n\tIf this observation happens to be true, the presence of PetC protein family in a newly sequenced cyanobacterial genome along with specific features of central carbon metabolism could be used for prediction of its growth capabilities.\r\n"],"role_id":["Cytochrome b6-f complex subunit V (PetG)","Cytochrome b6-f complex subunit VI (PetL)","Cytochrome b6-f complex subunit, apocytochrome f","Cytochrome b6-f complex iron-sulfur subunit PetC1 (Rieske iron sulfur protein EC 1.10.9.1)","Cytochrome b6-f complex alternative Rieske iron sulfur protein PetC2","Cytochrome b6-f complex alternative Rieske iron sulfur protein PetC3","Cytochrome b6-f complex subunit, cytochrome b6","Cytochrome b6-f complex subunit, cytochrome b6, putative","Cytochrome b6-f complex subunit IV (PetD)","Cytochrome b6-f complex subunit VII (PetM)","Cytochrome b6-f complex subunit VIII (PetN)"],"_version_":1809284005126733800},{"class":"Prophages, Transposable elements, Plasmids","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"076c822f-e519-44d4-9ee7-6c4365a1cdae","subclass":"Pathogenicity islands","subsystem_id":"Listeria_Pathogenicity_Island_LIPI-1_extended","subsystem_name":"Listeria Pathogenicity Island LIPI-1 extended","superclass":"Miscellaneous","role_name":["Virulence regulatory factor PrfA","Phosphatidylinositol-specific phospholipase C (EC 4.6.1.13)","Thiol-activated cytolysin","Zinc metalloproteinase aureolysin (EC 3.4.24.29)","Actin-assembly inducing protein ActA precursor","Broad-substrate range phospholipase C (EC 3.1.4.3)","Distant similarity with viral glycoprotein gp160 of HIV type 1","virulence cluster protein A VclA","virulence cluster protein B VclB"],"notes":["Listeria main pathogenicity island LIPI-1 comprises 7 ORFs from lmo0200 to lmo0206 and carries virulence genes essential for intracellular parasitism.  LIPI-1 is stably inserted at the same locus in genomes of pathogenic L. monocytogenes and L. ivanovii.  It is missing from genomes of nonpathogenic L. innocua and L. welshimeri (apparently due to a deletion), and is corrupt in L. seeligeri.  LIPI-1 has G+C composition similar to that of listerial core genome, lacks obvious traces of mobility factors, and its insertion locus is devoid of usual integration signals, such as tRNAs, repeats, etc (however, 2 small ORFs distantly related to viral proteins are located at its extreme right end).  LIPI-1 appears ancient, acquired by common Listeria ancestor.\r\n\r\nAn attempt to extend this subsystem in order to identify related virulence factors in other microbial pathogens has revealed orthologs for the majority of Listeria proteins located within LIPI-1 in several Gram(+) pathogens - with a notable exception of ActA, which has no prokaryotic homologs.  Surface protein ActA is necessary and sufficient for Listeria�s unique actin-based motility within the cytoplasm of an infected cell.  ActA causes polymerization of host actin filaments at one pole of the bacterium into long tails that propel the bacteria through the cytoplasm. (Listeria and Shigella flexneri are the only two unrelated facultative intracellular pathogens which spread from cell to cell by using this mode of intracellular movement.  However, IcsA (VirG) surface protein in S. flexneri required for this motility has no sequence similarity with ActA.)   Evolutionary origin of ActA is not clear, but it contains functional domains that mimic the natural role of the mammalian Arp2/3 complex-activating proteins of the WASP/Scar family, involved in dynamic remodeling of actin cytoskeleton. \r\n\r\nVariant codes:\r\n\r\n 1 = full length pathogenicity island LIPI-1 is present in a genome\r\n 9 = Listeria species with LIPI-1 completely or partially deleted\r\n 2 = homolog of one or more proteins from LIPI-1 can be asserted in an organism other than Listeria\r\n-1 = no homologs of any LIPI-1 proteins are evident in a genome\r\n\r\nReferences:\r\n1. Vazquez-Boland JA, Dominguez-Bernal G, Gonzalez-Zorn B, Kreft J, Goebel W. 2001. Pathogenicity islands and virulence evolution in Listeria. Microbes Infect. 3(7):571-584.  PMID: 11418331\r\n\r\n2. Glaser P, et al., and Cossart P.  2001. Comparative genomics of Listeria species.\r\nScience 294(5543):849-852.  PMID: 11679669\r\n\r\n3. A.A. Salyers and D.D. Whiott.  Bacterial Pathogenesis. 2002. ASM Press, Herndon, VA.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n"],"role_id":["Virulence regulatory factor PrfA","Phosphatidylinositol-specific phospholipase C (EC 4.6.1.13)","Thiol-activated cytolysin","Zinc metalloproteinase aureolysin (EC 3.4.24.29)","Actin-assembly inducing protein ActA precursor","Broad-substrate range phospholipase C (EC 3.1.4.3)","Distant similarity with viral glycoprotein gp160 of HIV type 1","virulence cluster protein A VclA","virulence cluster protein B VclB"],"_version_":1809284005130928000},{"class":"Membrane Transport","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"The major facilitator superfamily (MFS) is the largest known superfamily of secondary carriers found in the biosphere. It is ubiquitously distributed throughout virtually all currently recognized organismal phyla. This superfamily currently (2012) consists of 74 families, each of which is usually concerned with the transport of a certain type of substrate. Many of these families, defined phylogenetically, do not include even a single member that is functionally characterized. (PMID:22458847) \r\n\r\nE. coli K-12 contains 70 MFS transporters, 15 of which may be considered drug exporters, as they belong to families 2 and 3 (http://www.membranetransport.org/), which are composed of 12-TMS (transmembrane segment) and 14-TMS members, respectively, of drug/H+ antiporters (37, 130). Most of them, however, are free-standing transporters located in the IM and transport drugs from the cytosol to only the periplasm. Because most antimicrobial agents reach the cytosol usually by diffusion across the membrane bilayer, the pumped- out drug molecules have a good chance of reentering the cytosol through this free-diffusion process, and the transporters of this class are not expected to create high-level resistance (PMID: 25788514).\r\n\r\nFor this reason this Subsystem encodes only those MFS pumps, which (i) occur with their own periplasmic adaptor proteins and with OM channels (such as TolC) and presumably produce an efficient tripartite efflux system (PMID: 25788514) and (ii) are still uncharacterized.  Several characterized tripartite efflux systems of MFS family are encoded in separate Subsystems, for example, see: SS: \"Tripartite multidrug efflux systems (of MSF type) EmrKY-TolC and EmrAB-TolC\"\r\n\r\nTripartite efflux systems in Gram-negative bacteria are composed of:\r\n- an outer membrane factor (OMF) \r\n- and a periplasmic accessory protein (often called a membrane fusion protein)\r\n- an inner membrance pump (which can belong to one of several protein families: MFS, RND, or ABC).  \r\n\r\nNote, that ONLY tripartite efflux systems with inner membrance pumps of the MFS family are encoded in this SS.  The tripartite systems with inner membrance pumps of other types are encoded separately, for example, see the following Subsystems:\r\n\r\n- \"Tripartite multidrug efflux systems (of RND type) AcrAB-TolC and related transporters\"\r\n- \"Tripartite multidrug efflux systems (of RND type) MdtABC-TolC\"\r\n- \"Macrolide MacAB-TolC efflux pump transporter (of ABC type)\"\r\n- etc\r\n\r\n","id":"0797a059-f65e-4e30-9f04-624d68698722","subclass":"Multidrug efflux systems","subsystem_id":"Tripartite_multidrug_efflux_systems_(of_MFS_type)_in_Gram-negative_bacteria","subsystem_name":"Tripartite multidrug efflux systems (of MFS type) in Gram-negative bacteria","superclass":"Membrane Transport","role_name":["Efflux pump transporter (MSF type) of tripartite multidrug efflux system in Aquificae","Efflux transport system, outer membrane factor (OMF) in Aquificae","Membrane fusion component of MSF-type tripartite multidrug efflux system","Inner-membrane proton/drug antiporter (MSF type) of tripartite multidrug efflux system","Efflux transport system, outer membrane factor (OMF) in Bacteroidetes/Chlorobi","Outer membrane component of tripartite multidrug resistance system","Inner membrane component of tripartite multidrug resistance system","Membrane fusion component of tripartite multidrug resistance system"],"notes":["References\r\n\r\nLi XZ, Plesiat P, Nikaido H. 2015. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev. 2015 Apr;28(2):337-418. PMID: 25788514\r\n\r\nReddy VS1, Shlykov MA, Castillo R, Sun EI, Saier MH Jr. 2012. The major facilitator superfamily (MFS) revisited. FEBS J. 2012 Jun;279(11):2022-35. PMID: 22458847 (this study used SEED)\r\n\r\nZgurskaya HI1, Krishnamoorthy G, Tikhonova EB, Lau SY, Stratton KL. 2003. Mechanism of antibiotic efflux in Gram-negative bacteria. Front Biosci, 8:s862-73. PMID: 12957812\r\n\r\nBorges-Walmsley MI1, McKeegan KS, Walmsley AR. 2003. Structure and function of efflux pumps that confer resistance to drugs. Biochem J. 2003 Dec 1;376(Pt 2):313-38.  PMID:  13678421\r\n\r\nNishino K1, Yamaguchi A.  2001.  Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol. 2001 Oct;183(20):5803-12.  PMID:11566977\r\n\r\n"],"role_id":["Efflux pump transporter (MSF type) of tripartite multidrug efflux system in Aquificae","Efflux transport system, outer membrane factor (OMF) in Aquificae","Membrane fusion component of MSF-type tripartite multidrug efflux system","Inner-membrane proton/drug antiporter (MSF type) of tripartite multidrug efflux system","Efflux transport system, outer membrane factor (OMF) in Bacteroidetes/Chlorobi","Outer membrane component of tripartite multidrug resistance system","Inner membrane component of tripartite multidrug resistance system","Membrane fusion component of tripartite multidrug resistance system"],"_version_":1809284005133025300},{"class":"Cofactors, Vitamins, Prosthetic Groups","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Tetrapyrroles and their derivatives play an essential role in all living organisms. They are involved in many metabolic processes, such as energy transfer, catalysis, and signal transduction.  In eukaryotes, the synthesis of tetrapyrroles is restricted to heme, siroheme, chlorophyll and bilins.  Prokaryotes additionally form most complicated tetrapyrroles, such as corrinoids, heme d1 and coenzyme F430.  An abundant and ubiquitous representative of this group of compounds is heme, a cyclic tetrapyrrole that contains a centrally chelated Fe.\r\n\r\nReferences:\r\n\r\n1. Dailey HA, Gerdes S, Dailey TA, Burch JS, Phillips JD. 2015. Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. PNAS, 112(7):2210-5. PMID:25646457\r\n\r\n2. Bali S, Palmer DJ, Schroeder S, Ferguson SJ, Warren MJ. 2014. Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1.\r\nCell Mol Life Sci, 71(15):2837-63. PMID:24515122\r\n\r\n3. N. Frankenberg, J. Moser, and D. Jahn. 2003.  Bacterial heme biosynthesis and its biotechnological application. Appl Microbiol Biotechnol 63: 115�127.\r\n\r\n4. H. A. Dailey. 2002.  Terminal steps of haem biosynthesis. Biochemical Society Transactions 30: 590-595.\r\n\r\n5. D.V. Vavilin and W.F.J. Vermaas. 2002.  Regulation of the tetrapyrrole biosynthetic pathway leading to heme and chlorophyll in plants and cyanobacteria. Physiologia Plantarum 115: 9�24. \r\n\r\n6. M.M. Kolko, L.A. Kapetanovich, and J.G. Lawrence. 2001. Alternative Pathways for Siroheme Synthesis in Klebsiella aerogenes. J. Bact 183: 328�335\r\n","id":"148d7bb9-bb46-408d-adb2-ac42aa9d3de3","subclass":"Tetrapyrroles","subsystem_id":"Heme_Biosynthesis:_protoporphyrin-,_coproporphyrin-_and_siroheme-dependent_pathways","subsystem_name":"Heme Biosynthesis: protoporphyrin-, coproporphyrin- and siroheme-dependent pathways","superclass":"Metabolism","role_name":["Glutamyl-tRNA synthetase (EC 6.1.1.17)","Glutamyl-tRNA reductase (EC 1.2.1.70)","Glutamate-1-semialdehyde 2,1-aminomutase (EC 5.4.3.8)","5-aminolevulinate synthase (EC 2.3.1.37)","Porphobilinogen synthase (EC 4.2.1.24)","Porphobilinogen deaminase (EC 2.5.1.61)","Uroporphyrinogen-III synthase (EC 4.2.1.75)","Uroporphyrinogen-III synthase in Bacteroidetes, divergent, putative (EC 4.2.1.75)","Uroporphyrinogen-III synthase in Rickettsia, divergent, putative (EC 4.2.1.75)","Putative uroporphyrinogen-III synthase (EC 4.2.1.75), related to YjjA (in BS)","Uroporphyrinogen-III methyltransferase (EC 2.1.1.107)","Precorrin-2 oxidase (EC 1.3.1.76)","Sirohydrochlorin ferrochelatase activity of CysG (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase SirB (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase activity of CbiK (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase CbiX, alphaprotobacterial (EC 4.99.1.4)","Uroporphyrinogen III decarboxylase (EC 4.1.1.37)","Coproporphyrinogen III oxidase, aerobic (EC 1.3.3.3)","Coproporphyrinogen III oxidase, oxygen-independent (EC 1.3.99.22)","Protoporphyrinogen IX oxidase, oxygen-independent, HemG (EC 1.3.-.-)","Protoporphyrinogen IX oxidase, novel form, HemJ (EC 1.3.-.-)","Ferrochelatase, protoheme ferro-lyase (EC 4.99.1.1)","Coproheme decarboxylase HemQ (no EC)","putative monooxygenase domain","Protoporphyrinogen IX oxidase, aerobic, HemY (EC 1.3.3.4)","Coproporphyrin ferrochelatase (EC 4.99.1.-)","Siroheme decarboxylase AhbA, alternate heme biosynthesis pathway","Siroheme decarboxylase AhbB, alternate heme biosynthesis pathway","Radical SAM heme biosynthesis protein AhbC, 12,18-didecarboxysirohaem deacetylase","Radical SAM heme biosynthesis protein AhbD, Fe-coproporphyrin III decarboxylase","Nitrite reductase (EC 1.7.2.1)","Heme d1 biosynthesis protein NirJ","Heme d1 biosynthesis protein NirF","Heme d1 biosynthesis protein NirD","Heme d1 biosynthesis protein NirG","Heme d1 biosynthesis protein NirL","Heme d1 biosynthesis protein NirH"],"role_id":["Glutamyl-tRNA synthetase (EC 6.1.1.17)","Glutamyl-tRNA reductase (EC 1.2.1.70)","Glutamate-1-semialdehyde 2,1-aminomutase (EC 5.4.3.8)","5-aminolevulinate synthase (EC 2.3.1.37)","Porphobilinogen synthase (EC 4.2.1.24)","Porphobilinogen deaminase (EC 2.5.1.61)","Uroporphyrinogen-III synthase (EC 4.2.1.75)","Uroporphyrinogen-III synthase in Bacteroidetes, divergent, putative (EC 4.2.1.75)","Uroporphyrinogen-III synthase in Rickettsia, divergent, putative (EC 4.2.1.75)","Putative uroporphyrinogen-III synthase (EC 4.2.1.75), related to YjjA (in BS)","Uroporphyrinogen-III methyltransferase (EC 2.1.1.107)","Precorrin-2 oxidase (EC 1.3.1.76)","Sirohydrochlorin ferrochelatase activity of CysG (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase SirB (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase activity of CbiK (EC 4.99.1.4)","Sirohydrochlorin ferrochelatase CbiX, alphaprotobacterial (EC 4.99.1.4)","Uroporphyrinogen III decarboxylase (EC 4.1.1.37)","Coproporphyrinogen III oxidase, aerobic (EC 1.3.3.3)","Coproporphyrinogen III oxidase, oxygen-independent (EC 1.3.99.22)","Protoporphyrinogen IX oxidase, oxygen-independent, HemG (EC 1.3.-.-)","Protoporphyrinogen IX oxidase, novel form, HemJ (EC 1.3.-.-)","Ferrochelatase, protoheme ferro-lyase (EC 4.99.1.1)","Coproheme decarboxylase HemQ (no EC)","putative monooxygenase domain","Protoporphyrinogen IX oxidase, aerobic, HemY (EC 1.3.3.4)","Coproporphyrin ferrochelatase (EC 4.99.1.-)","Siroheme decarboxylase AhbA, alternate heme biosynthesis pathway","Siroheme decarboxylase AhbB, alternate heme biosynthesis pathway","Radical SAM heme biosynthesis protein AhbC, 12,18-didecarboxysirohaem deacetylase","Radical SAM heme biosynthesis protein AhbD, Fe-coproporphyrin III decarboxylase","Nitrite reductase (EC 1.7.2.1)","Heme d1 biosynthesis protein NirJ","Heme d1 biosynthesis protein NirF","Heme d1 biosynthesis protein NirD","Heme d1 biosynthesis protein NirG","Heme d1 biosynthesis protein NirL","Heme d1 biosynthesis protein NirH"],"_version_":1809284005136171000,"notes":["See below (Under \"Variants\") the descriptions of the current variant codes.\r\nOld detailed variant codes were as follows:\r\n\r\nA. The first  digits in a variant code reflect the type of 5-aminolevulinic acid biosynthesis present in an organism:\r\n1***: 5-aminolevulinic acid biosynthesis via C5-pathway\r\n2***: 5-aminolevulinic acid biosynthesis via Shemin pathway\r\n3***: both pathways are present in the organism\r\n8***: both pathways are absent in the organism\r\n\r\nThe common precursor of all marcocyclic and linear tetrapyrroles, 5-aminolevulinic acid (ALA), is synthesized by two alternative unrelated routes called the C5-pathway (Beale and Castelfranco 1973; Jahn et al. 1992) and the Shemin pathway (Shemin and Russell 1953).  The C5 pathway, which is found in most bacteria, archaea and plants, starts from the C5-skeleton of glutamate, ligated to tRNAGlu. Some alpha-proteobacteria, fungi, and animals synthesize 5-aminolevulinate via Shemin pathway by condensation of succinyl-CoA with glycine.  Coexistence of both pathways in a single organism is very rare.\r\n\r\n\r\nB. Universal steps in biosynthesis of tetrapyrroles: condensation of 8 molecules of 5-aminolevulinic acid to form Uroporphyrinogen III.   No variants detected so far -- hence, no representation in variant codes. However, HemD homologs are missing in quite a few species, including Synechococcus elongatus PCC 7942, Caulobacter crescentus CB15, Rickettsiae, Leptospira interrogans, Acinetobacter sp. ADP1, Cytophaga hutchinsonii, etc.\r\n\r\nUroporphyrinogen III (UroIII) is the first cyclic tetrapyrrole intermediate in the pathway and is a precursor both to oxidized tetrapyrroles, such as haem and chlorophylls, and to reduced tetrapyrroles, such as sirohaem, vitamin B12 and haem d1.  \r\n\r\nC. Terminal steps of protoheme biosynthesis: Uroporphyrinogen III to Protoheme.\r\n\r\nVariations within these steps are encoded in the 2d and 3d digits of variant codes. The second digit  describes the type of coproporphyrinogen III oxidase present in a genome:\r\n*1**: CPOae,  oxygen-dependent coproporphyrinogen III oxidase (EC 1.3.3.3, HemF) catalyzes oxidative   decarboxylation of coproporphyrinogen III to protoporphyrinogen IX with oxygen as the electron acceptor, \r\n*2**: CPOan, oxygen-independent coproporphyrinogen III oxidase (HemN or/and HemZ),\r\n*3**: Both forms of coproporphyrinogen III oxidase (aerobic and anaerobic) are present in an organism.\r\n*9**: Both forms of coproporphyrinogen III oxidase (aerobic and anaerobic) are missing.\r\n\r\nNoteworthy: CPOan homologs seem to be present in many genomes where all other porphyrin biosynthetic genes are absent.\r\n\r\nThe 3d digit reflects the type of protoporphyrinogen oxidase (PPO), catalyzing the penultimate step in heme biosynthsis:\r\n**1*: Organisms containing oxygen-dependent protoporphyrinogen oxidase (PPOae)\r\n**2*: Organisms containing oxygen-independent protoporphyrinogen oxidase (PPOan)\r\n**3*: Both forms of PPO, aerobic and anaerobic, are present in an organism (uncommon)\r\n**9*: Both known genes for protoporphyrinogen oxidase are missing\r\n\r\nAs with CPO, two forms of PPO exist: one oxygen-dependent and one oxygen-independent.  In bacteria where these two PPOs have been identified, the gene for the oxygen dependent form is hemY, and that for the oxygen-independent form is called hemG.  Unlike with CPO HemN and HemF, only a single form of PPO is generally found in a given cell.  Facultative organisms such as E. coli possess only HemG. HemG protein interacts with the cell�s respiratory chain to eliminate the reducing equivalents acquired by protoporphyrinogen oxidation. The oxygen-independent protoporphyrinogen oxidase (PPOan) present in many Gram-positive species (including Bacillus subtilis) is similar to the eukaryotic enzyme. HemY contains a flavin cofactor and utilizes molecular oxygen as a terminal electron acceptor (Hansson and Hederstedt 1994). \r\nHowever, hemG or hemY genes are not found in all heme-synthesizing prokaryotes. A recognizable PPO gene (hemG or hemY) is missing in roughly half of heme-synthesizing microorganisms.\r\n\r\nNote:  to further complicate things, an E. coli gene located within hem operon has also been named hemY.  However, it has no homology with B. subtilis hemY and its function is unknown.  Since it's homologs are clustered with hem genes in many genomes, the corresponding protein has been included in this Subsystem (abbreviated as EcHemY).\r\n\r\n\r\nD: The fourth digit shows the presence or absence of Siroheme Biosynthetic genes in a genome:\r\n\r\n***1:  all the necessary genes of siroheme biosynthesis are present in a genome\r\n***9:  all known genes of siroheme biosynthesis are absent\r\n***8:  siroheme biosynthesis can be asserted tentatively, but at least one of the required enzymes could not be detected, most often Precorrin-2 oxidase (missing gene??) \r\n\r\nBiosynthesis of siroheme  (branching off the heme biosynthetic pathway at the level of Uroporphyrinogen-III) has been included in this Subsystem because genes encoding it are often clustered with genes of heme biosynthesis.  Furthermore, UroIII methyltransferase (EC 2.1.1.107) catalyzing the first step in siroheme biosynthesis is often fused with UroIII synthase (EC 4.2.1.75) � one of the enzymes of heme biosynthetic pathway (its universal steps).  Interestingly, while in many Gram-Positive bacteria (Bacillus, Clostridia, Listeria, Fusobacteria, and other genera) the order of the two domains in fused protein is as follows: methyltransferase/synthase, but the order is reversed in Burkholderiaceae, indicating that this fusion has occurred independently at least twice in evolution. \r\n\r\nFurthermore, all the three steps of sirohaem biosynthesis  (methylation, oxidation, Fe-chelation) are catalyzed by a single protein, siroheme synthase, the product of the cysG gene (fusion again!) in most Siroheme-containing organisms.   Interestingly, in some Gram-Positive groups (Bacillus, Clostridia, Listeria) a \"short version\" of siroheme synthase is present, which contains  Precorrin-2 oxidase (EC 1.3.1.76) and Ferrochelatase (EC 4.99.1.4) domeins, but not the C-terminal UroIII methyltransferase (EC 2.1.1.107) domein.  The reason for the strong tendency of all siroheme biosynthetic genes to be fused together is intriguing (see Forum posting for some ideas).  \r\n\r\nAnother puzzle:  the first step in synthesis of sirohaem, (as well as vitamin B12 and haem d1) is an S-adenosylmethionine-dependent methylation of UroIII to form precorrin-2.  Surprisingly, UroIII methyltransferase is often present in organisms that lack any known genes encoding downstream steps in biosynthesis of these tertapyrroles.  \r\n\r\nThe iron-chelating siroheme is required for the six-electron transfer reactions during assimilatory nitrite or sulfite reduction (Raux et al. 2003) and CysG is often co-localizes with genes encoding nitrite or sulfite reductases.\r\n\r\nArchaea have NOT been looked into in detail yet - sorry.\r\n\r\nThis SS is further discussed in the Supplementary materials for the paper (Overbeek et al., 2005) at \r\nhttp://www.theseed.org/SubsystemStories/index.html\r\n\r\n"]},{"class":"Phosphate Metabolism","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"1679bde5-76d1-40bd-9524-5b368f37af8d","subclass":"Phosphonate and phosphinate","subsystem_id":"Phosphonate_(phosphite)_dehydrogenase","subsystem_name":"Phosphonate (phosphite) dehydrogenase","superclass":"Metabolism","role_name":["LysR-family transcriptional regulator PtxE, associated with phosphonate utilization","Phosphonate ABC transporter ATP-binding protein PtxA (TC 3.A.1.9.1)","Phosphonate ABC transporter substrate-binding protein PtxB (TC 3.A.1.9.1)","Phosphonate ABC transporter permease protein PtxC (TC 3.A.1.9.1)","Phosphonate dehydrogenase (EC 1.20.1.1)"],"notes":["\n"],"role_id":["LysR-family transcriptional regulator PtxE, associated with phosphonate utilization","Phosphonate ABC transporter ATP-binding protein PtxA (TC 3.A.1.9.1)","Phosphonate ABC transporter substrate-binding protein PtxB (TC 3.A.1.9.1)","Phosphonate ABC transporter permease protein PtxC (TC 3.A.1.9.1)","Phosphonate dehydrogenase (EC 1.20.1.1)"],"_version_":1809284005141414000},{"class":"Prophages, Transposable elements, Plasmids","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"Remarkably, nearly all bacterial toxins associated with specific clinical conditions (toxinoses) are encoded by mobile genetic elements. Examples are the toxins responsible for diphtheria, anthrax, tetanus, botulism, cholera, toxic shock,  scarlet fever, exfoliative dermatitis, food poisoning, travelers diarrhea, shigella dysentery, necrotizing pneumonia, and  others. An interesting example of this phenomenon is the family of related staphylococcal pathogenicity islands (SaPI) encoding superantigens (SAgs). These are 15�20 kb elements that occupy constant positions in the chromosomes of toxigenic strains, and are characterized by certain phage-related features, namely genes encoding integrases, helicases,  and terminases, and the presence of flanking direct repeats (Novick, 2003).  The majority carry endotoxin genes, but some seem to harbor other genes potentially conferring selective advantage, e.g. SaGIm encodes a homolog of a ferrichrome-binding subunit (FhuD) of an ABC transporter (Kuroda et al., 2001).  The prototype element for the entire group, SaPI1 of Staphylococcus aureus RN4282, located near tyrB, encodes Toxic shock syndrome toxin (TSST-1) plus two other SAgs, SEK and SEL (Ruzin et al., 2001).  Some members of the family are capable of specific interactions with certain phages leading to excision, amplification, and encapsidation.  Notably, some copies are located in the proximity of prophages.  \r\n\r\nWith these elements being very variable, we relied mostly on their specific integration sites (att) in the S. aureus genome for classification (see Table 1 - access via green \"Illustrations\" tab on top of this page).  For the published elements we tried to keep the names suggested in the original publication, for all others - names were projected in accordance with their att sites. \r\nNote, that if you view Subsystem spreadsheet with �show clusters� activated, the clustering of the first gene of each element (Integrase, columns 6,7) with one of the possible integration sites (columns 1-5) will reveal the element type.   There can be more than one element present per genome.   Also, in several strains only a degenerated integrase gene is be present at the att site (a scar from previous integration events??)\r\n","id":"0a5d1938-2915-46a5-90dd-0892fffe3d5f","subclass":"Pathogenicity islands","subsystem_id":"Staphylococcal_pathogenicity_islands_SaPI","subsystem_name":"Staphylococcal pathogenicity islands SaPI","superclass":"Miscellaneous","role_name":["CI-like repressor, superantigen-encoding pathogenicity islands SaPI","Cro-like repressor, superantigen-encoding pathogenicity islands SaPI","Degenerate integrase, superantigen-encoding pathogenicity islands SaPI","Ferrichrome-binding periplasmic protein precursor in superantigen-encoding pathogenicity islands SaPI","GMP synthase [glutamine-hydrolyzing] (EC 6.3.5.2)","Heat shock protein 60 kDa family chaperone GroEL","Hypothetical MW0753 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical MW0754 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0365 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0369 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0371 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0372 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0385 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0786 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0787 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0788 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0793 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0794 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0795 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0796 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0797 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0798 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0799 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0801 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0808 homolog, near pathogenicity islands SaPI att-site","Hypothetical SAV2026 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV2027 homolog in superantigen-encoding pathogenicity islands SaPI","Integrase, superantigen-encoding pathogenicity islands SaPI","Methionine ABC transporter substrate-binding protein","Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI","Putative primase, superantigen-encoding pathogenicity islands SaPI","Putative terminase, superantigen-encoding pathogenicity islands SaPI","SSU ribosomal protein S18p","Secreted protein Ear, superantigen-encoding pathogenicity islands SaPI","Superantigen enterotoxin SEB","Superantigen enterotoxin SEK","Superantigen enterotoxin SEL","Toxic shock syndrome toxin 1 (TSST-1)","tmRNA-binding protein SmpB"],"notes":["References\r\n\r\n1. Fitzgerald, J.R., Monday, S.R., Foster, T.J., Bohach, G.A., Hartigan, P.J., Meaney, W.J., Smyth, C.J., 2001. Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens. J. Bacteriol. 183, 63�70. \r\n\r\n2. Holden MT, Feil EJ, Lindsay JA, et al., and Parkhill J.  2004. Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A. 101(26):9786-91.\r\n\r\n3. Kuroda M, Ohta T, Uchiyama I, et al., Ogasawara N, Hayashi H, Hiramatsu K.  2001. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet, 357(9264):1225-40.\r\n\r\n4. Novick RP. 2003.  Mobile genetic elements and bacterial toxinoses: the superantigen-encoding pathogenicity islands of Staphylococcus aureus. Plasmid 49(2):93-105.\r\n\r\n5. Ruzin, A., Lindsay, J., Novick, R.P., 2001. Molecular genetics of SaPI1�a mobile pathogenicity island in Staphylococcus aureus. Mol. Microbiol. 41, 365�377. \r\n\r\n6. Yarwood J.M., J.K. McCormick, M. L. Paustian, P.M. Orwin, V. Kapur, and P. M. Schlievert.  2002.  Characterization and expression analysis of Staphylococcus aureus pathogenicity island 3.  Implications for the evolution of staphylococcal pathogenicity islands. J. Biol. Chem. 277(15):13138-13147\r\n\r\n"],"role_id":["CI-like repressor, superantigen-encoding pathogenicity islands SaPI","Cro-like repressor, superantigen-encoding pathogenicity islands SaPI","Degenerate integrase, superantigen-encoding pathogenicity islands SaPI","Ferrichrome-binding periplasmic protein precursor in superantigen-encoding pathogenicity islands SaPI","GMP synthase [glutamine-hydrolyzing] (EC 6.3.5.2)","Heat shock protein 60 kDa family chaperone GroEL","Hypothetical MW0753 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical MW0754 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0365 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0369 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0371 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0372 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAR0385 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0786 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0787 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0788 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0793 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0794 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0795 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0796 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0797 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0798 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0799 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0801 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV0808 homolog, near pathogenicity islands SaPI att-site","Hypothetical SAV2026 homolog in superantigen-encoding pathogenicity islands SaPI","Hypothetical SAV2027 homolog in superantigen-encoding pathogenicity islands SaPI","Integrase, superantigen-encoding pathogenicity islands SaPI","Methionine ABC transporter substrate-binding protein","Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI","Putative primase, superantigen-encoding pathogenicity islands SaPI","Putative terminase, superantigen-encoding pathogenicity islands SaPI","SSU ribosomal protein S18p","Secreted protein Ear, superantigen-encoding pathogenicity islands SaPI","Superantigen enterotoxin SEB","Superantigen enterotoxin SEK","Superantigen enterotoxin SEL","Toxic shock syndrome toxin 1 (TSST-1)","tmRNA-binding protein SmpB"],"_version_":1809284005142462500},{"class":"Nitrogen Metabolism","date_inserted":"2018-03-21T18:40:25.135Z","date_modified":"2018-03-21T18:40:25.135Z","description":"\n","id":"1981aa26-22c1-483e-afd2-a6300261e676","subsystem_id":"Nitrogen_regulation_orphans","subsystem_name":"Nitrogen regulation orphans","superclass":"Metabolism","role_name":["[Protein-PII] uridylyltransferase (EC 2.7.7.59)","[Protein-PII]-UMP uridylyl-removing enzyme","Ammonium transporter","Nitrogen regulatory protein P-II, GlnK","Nitrogen regulatory protein P-II","Putative regulatory protein, P-II family","Nitrogen regulation protein NtrB (EC 2.7.13.3)","Nitrogen regulation protein NR(I), GlnG (=NtrC)","Glutamine synthetase adenylyl-L-tyrosine phosphorylase (EC 2.7.7.89)","Glutamate-ammonia-ligase adenylyltransferase (EC 2.7.7.42)","Glutamine synthetase type I (EC 6.3.1.2)","Glutamine synthetase type II, eukaryotic (EC 6.3.1.2)","Glutamine synthetase type III, GlnN (EC 6.3.1.2)","Glutamine synthetase type III (EC 6.3.1.2)","Glutamine synthetase, clostridia type (EC 6.3.1.2)","Putative glutamine synthetase, Rickettsiales type (EC 6.3.1.2)","Assimilatory nitrate reductase large subunit (EC 1.7.99.4)","Nitrite reductase [NAD(P)H] large subunit (EC 1.7.1.4)","Nitrite reductase [NAD(P)H] small subunit (EC 1.7.1.4)","Nitrogenase (molybdenum-iron) alpha chain (EC 1.18.6.1)","Nitrogenase (vanadium-iron) alpha chain (EC 1.18.6.1)","Nitrogenase (iron-iron) alpha chain (EC 1.18.6.1)","Nitrogen regulatory protein P-II, nitrogen-fixation associated, subunit A","Nitrogen regulatory protein P-II, nitrogen-fixation associated, subunit B","Putative regulatory protein clustered with metal efflux genes, P-II family","Nitrogen regulatory protein GltF"],"notes":["P-II indirectly controls the transcription of the glutamine synthetase gene (glnA). P-II prevents NR-II-catalyzed conversion of NR-I to NR-I-phosphate, the transcriptional activator of GlnA. When P-II is uridylylated to P-II-UMP, these events are reversed. When the ratio of Gln to 2-ketoglutarate decreases, P-II is uridylylated to P-II-UMP, which causes the deadenylation of glutamine synthetase by GlnE, so activating the enzyme.\n"],"role_id":["[Protein-PII] uridylyltransferase (EC 2.7.7.59)","[Protein-PII]-UMP uridylyl-removing enzyme","Ammonium transporter","Nitrogen regulatory protein P-II, GlnK","Nitrogen regulatory protein P-II","Putative regulatory protein, P-II family","Nitrogen regulation protein NtrB (EC 2.7.13.3)","Nitrogen regulation protein NR(I), GlnG (=NtrC)","Glutamine synthetase adenylyl-L-tyrosine phosphorylase (EC 2.7.7.89)","Glutamate-ammonia-ligase adenylyltransferase (EC 2.7.7.42)","Glutamine synthetase type I (EC 6.3.1.2)","Glutamine synthetase type II, eukaryotic (EC 6.3.1.2)","Glutamine synthetase type III, GlnN (EC 6.3.1.2)","Glutamine synthetase type III (EC 6.3.1.2)","Glutamine synthetase, clostridia type (EC 6.3.1.2)","Putative glutamine synthetase, Rickettsiales type (EC 6.3.1.2)","Assimilatory nitrate reductase large subunit (EC 1.7.99.4)","Nitrite reductase [NAD(P)H] large subunit (EC 1.7.1.4)","Nitrite reductase [NAD(P)H] small subunit (EC 1.7.1.4)","Nitrogenase (molybdenum-iron) alpha chain (EC 1.18.6.1)","Nitrogenase (vanadium-iron) alpha chain (EC 1.18.6.1)","Nitrogenase (iron-iron) alpha chain (EC 1.18.6.1)","Nitrogen regulatory protein P-II, nitrogen-fixation associated, subunit A","Nitrogen regulatory protein P-II, nitrogen-fixation associated, subunit B","Putative regulatory protein clustered with metal efflux genes, P-II family","Nitrogen regulatory protein GltF"],"_version_":1809284005146656800}]