As text, or see rules and steps
# Arginine utilization in GapMind is based on MetaCyc pathways # L-arginine degradation I via arginase (metacyc:ARGASEDEG-PWY); # II via arginine succinyltransferase (metacyc:AST-PWY), # III via arginine decarboxylase and agmatinase (metacyc:PWY0-823), # IV via arginine decarboxylase and agmatine deiminase (metacyc:ARGDEG-III-PWY), # V via arginine deiminase (metacyc:ARGDEGRAD-PWY), # VI (arginase 2, metacyc:ARG-PRO-PWY), # VII (arginase 3, metacyc:ARG-GLU-PWY), # VIII via arginase oxidase (metacyc:ARGDEG-IV-PWY), # IX via arginine:pyruvate transaminase (metacyc:PWY-5742), # X via arginine monooxygenase (metacyc:ARGDEG-V-PWY), # XIII via proline (metacyc:PWY-8187), # and XIV via D-ornithine (metacyc:PWY-6344). # Common intermediates are L-ornithine or L-proline. # GapMind does not include pathways XI (metacyc:PWY-5024), which is poorly understood, # or XII (metacyc:PWY-7523), which is not reported in prokaryotes. # Many ABC transporters are known for arginine, including # E. coli artJQMP (which is specific for arginine) and E. coli hisQPM-argT (also transports lysine, ornithine) # These systems are generally homologous, but the two permease components also similar to each other. # To simplify the analysis, these were clustered at 40% identity instead of the usual 30% identity. # Distantly related proteins from Chlamydia (uniprot:ARTJ_CHLTR, uniprot:ARTJ_CHLPN) are annotated as artJ but # are not actually characterized, and the other components of this # system seem to be absent. So Chlamydial "artJ" were not included. # Ignore hisJ (CH_018185) from Salmonella and the P. fluorescens lysine transporter (AO356_09900), which # has a subtle defect on arginine and may well transport it, and close homologs in other Pseudomonas. # In Marinobacter adhaerens, the SBP (HP15_3031, E4PNW5) is somewhat diverged, but fitness data # confirms it is involved. artJ L-arginine ABC transporter, periplasmic substrate-binding component ArtJ/HisJ/ArtI/AotJ/ArgT curated:reanno::pseudo3_N2E3:AO353_03055 curated:CharProtDB::CH_002541 curated:CharProtDB::CH_003045 curated:CharProtDB::CH_014295 curated:SwissProt::P30859 curated:TCDB::O50181 curated:TCDB::P09551 curated:TCDB::Q9HU31 curated:reanno::BFirm:BPHYT_RS07735 curated:reanno::WCS417:GFF4245 curated:reanno::pseudo1_N1B4:Pf1N1B4_3431 curated:reanno::pseudo5_N2C3_1:AO356_18700 curated:reanno::pseudo6_N2E2:Pf6N2E2_5660 ignore:CharProtDB::CH_018185 ignore:reanno::pseudo5_N2C3_1:AO356_09900 ignore:reanno::pseudo6_N2E2:Pf6N2E2_2958 ignore:reanno::pseudo5_N2C3_1:AO356_05495 uniprot:E4PNW5 # ArtM and HisM are distantly related and were combined. # TC 1.B.6.2.7 / F9GZA7 is annotated as ArtM but seems more likely to be an outer membrane porin, # so it is not included. # Ignore closely related lysine transporters from P. fluorescens (which may well transport arginine; # AO356_09910 has a subtle defect in arginine utilization). artM L-arginine ABC transporter, permease component 1 (ArtM/HisM/AotM) curated:SwissProt::P0A2I7 curated:SwissProt::P0AEU3 curated:TCDB::O50183 curated:TCDB::Q9HU29 curated:reanno::BFirm:BPHYT_RS07680 curated:reanno::WCS417:GFF4243 curated:reanno::pseudo1_N1B4:Pf1N1B4_3433 curated:reanno::pseudo3_N2E3:AO353_03045 curated:reanno::pseudo5_N2C3_1:AO356_18710 curated:reanno::pseudo6_N2E2:Pf6N2E2_5662 curated:SwissProt::P0AE30 ignore:reanno::pseudo5_N2C3_1:AO356_09910 ignore:reanno::pseudo6_N2E2:Pf6N2E2_2960 ignore:reanno::pseudo5_N2C3_1:AO356_05505 # Ignore closely related lysine transporters from P. fluorescens (which may well transport arginine; # AO356_09895 has a subtle defect in arginine utilization) artP L-arginine ABC transporter, ATPase component ArtP/HisP/AotP/BgtA curated:CharProtDB::CH_003210 curated:SwissProt::P02915 curated:SwissProt::P0AAF6 curated:SwissProt::P54537 curated:TCDB::O30506 curated:TCDB::P73721 curated:TCDB::Q9HU32 curated:reanno::BFirm:BPHYT_RS07685 curated:reanno::pseudo1_N1B4:Pf1N1B4_3435 curated:reanno::pseudo3_N2E3:AO353_03040 curated:reanno::pseudo5_N2C3_1:AO356_18715 curated:reanno::pseudo6_N2E2:Pf6N2E2_5663 ignore:reanno::pseudo5_N2C3_1:AO356_09895 ignore:reanno::pseudo5_N2C3_1:AO356_05515 ignore:reanno::pseudo6_N2E2:Pf6N2E2_2962 # Ignore closely related lysine transporters in P. fluorescens (which may well transport arginine; # AO356_09905 has a subtle defect in arginine utilization) artQ L-arginine ABC transporter, permease component 2 (ArtQ/HisQ/AotQ) curated:TCDB::Q9HU30 curated:CharProtDB::CH_107317 curated:SwissProt::P0A2I9 curated:SwissProt::P0AE34 curated:SwissProt::P52094 curated:reanno::BFirm:BPHYT_RS07675 curated:reanno::WCS417:GFF4244 curated:reanno::pseudo1_N1B4:Pf1N1B4_3432 curated:reanno::pseudo3_N2E3:AO353_03050 curated:reanno::pseudo5_N2C3_1:AO356_18705 curated:reanno::pseudo6_N2E2:Pf6N2E2_5661 ignore:reanno::pseudo5_N2C3_1:AO356_09905 ignore:reanno::pseudo6_N2E2:Pf6N2E2_2959 ignore:reanno::pseudo5_N2C3_1:AO356_05500 # Transporters were identified using: # query: transporter:arginine:L-arginine:arg. arginine-transport: artJ artM artP artQ # In a artJMPQ-like system from Synechocystis, there is just one permease component fused to the # substrate-binding component. The fusion protein is known as BgtB or BgtAB. # (BgtA is the ATPase component and is included in the definition of ArtP.) bgtB L-arginine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB) curated:TCDB::P73544 curated:TCDB::Q8YSA2 arginine-transport: bgtB artP # braCDEFG from Rhizobium leguminosarum is described in glutamate.steps import glutamate.steps:braC braD braE braF braG arginine-transport: braC braD braE braF braG # Homomeric transporters rocE L-arginine permease curated:CharProtDB::CH_091412 curated:CharProtDB::CH_091699 curated:SwissProt::A0A1D8PPG4 curated:SwissProt::A0A1D8PPI5 curated:SwissProt::P39137 curated:SwissProt::Q59WB3 curated:SwissProt::Q59WU0 curated:SwissProt::Q5AG77 curated:TCDB::P43059 arginine-transport: rocE AAP3 L-arginine transporter AAP3 curated:BRENDA::Q86G79 arginine-transport: AAP3 CAT1 L-arginine transporter CAT1 curated:CharProtDB::CH_091324 arginine-transport: CAT1 Can1 L-arginine transporter Can1 curated:CharProtDB::CH_124821 arginine-transport: Can1 # Arginine/ornithine antiporters were ignored, as if ornithine is secreted during # growth on arginine then CO2 would be the effective carbon source. # Similarly, arginine/agmatine antiporters were ignored. # Arginine and lysine exporters (argO/yggA/lysE) were ignored # Eukaryotic ornithine carrier proteins were ignored, as these export ornithine/arginine # Vacuolar and lysosomal amino acid transporters were ignored # Outer membrane porins (oprD2 and "artM", TC 1.B.6.2.7) were ignored # A family of metazoan amino acid transporters (TC 2.A.3.8) was ignored # putrescine and GABA (gamma-aminobutyrate) are common intermediates. # MetaCyc does not list putrescine catabolism with glutamylated intermediates # (puuABCD) as a pathway for arginine (or citrulline) utilization, but it is logical that # arginine and citrulline can be converted to putrescine and catabolized this way. # Fitness data suggests that puuA is involved in arginine utilization # in Pseudomonas fluorescens FW300-N2E3 and in Pseudomonas simiae WCS417. import putrescine.steps:putrescine-degradation GABA-degradation # Proline is an intermediate import leucine.steps:atoB # acetyl-CoA acetyltransferase is part of glutaryl-CoA degradation import phenylacetate.steps:glutaryl-CoA-degradation # glutaryl-CoA is part of 5-aminovalerate degradation import lysine.steps:5-aminovalerate-degradation # 5-aminovalerate-degradation is part of proline degradation import proline.steps:proline-degradation # Pseudomonas aeruginsa has a heteromeric succinyltransferase (AruFG) that # is active on both arginine and ornithine (PMID:7523119, PMID:9393691). aruF ornithine/arginine N-succinyltransferase subunit AruAI (AruF) curated:CharProtDB::CH_107315 aruG ornithine/arginine N-succinyltransferase subunit AruAII (AruG) curated:BRENDA::P80358 arginine-succinyltransferase: aruF aruG # The other known arginine N-succinyltransferases have just one subunit # and are not known to be active on ornithine. astA arginine N-succinyltransferase EC:2.3.1.109 ignore:CharProtDB::CH_107315 ignore:BRENDA::P80358 arginine-succinyltransferase: astA # Marinobacter adhaerens HP15_3042 (GFF3099) is important for arginine biosynthesis # as well as catabolism, suggesting it is succinylornithine transaminase and # acetylornithine transaminase (similar to P. aeruginosa aruC) astC succinylornithine transaminase EC:2.6.1.81 curated:reanno::Marino:GFF3099 astD succinylglutamate semialdehyde dehydrogenase EC:1.2.1.71 astE succinylglutamate desuccinylase EC:3.5.1.96 # Ornithine is a common intermediate. It can be succinylated by aruFG and then # catabolized by the later steps of the arginine succinyltransferase pathway, via # aminotransferase, dehydrogenase, and desuccinylase reactions (see # PMC179677 and PMID:7523119). ornithine-degradation: aruF aruG astC astD astE rocD ornithine aminotransferase EC:2.6.1.13 rocA 1-pyrroline-5-carboxylate dehydrogenase EC:1.2.1.88 # Or as part of L-arginine degradation I, the # aminotransferase rocD converts ornithine to glutamate 5-semialdehyde, # which spontaneously converts to 1-pyrroline-5-carboxylate. A # dehydrogenase converts this to glutamate. ornithine-degradation: rocD rocA PRO3 pyrroline-5-carboxylate reductase EC:1.5.1.2 # Or 1-pyrroline-5-carboxylate can be reduced to proline by PRO3, as in L-arginine degradation VI. ornithine-degradation: rocD PRO3 proline-degradation ocd ornithine cyclodeaminase EC:4.3.1.12 # Alternatively, ornithine can be converted directly to proline # by ornithine cyclodeaminase (ocd). ornithine-degradation: ocd proline-degradation odc L-ornithine decarboxylase EC:4.1.1.17 # Or ornithine can be decarboxylated to putrescine by odc (metacyc:ORNDEG-PWY). ornithine-degradation: odc putrescine-degradation orr ornithine racemase EC:5.1.1.12 # D-ornithine aminomutase (5.4.3.5) is heteromeric oraS D-ornithine 4,5-aminomutase, alpha (S) subunit curated:SwissProt::E3PY96 ignore_other:5.4.3.5 oraE D-ornithine 4,5-aminomutase, beta (E) subunit curated:SwissProt::E3PY95 ignore_other:5.4.3.5 ord 2,4-diaminopentanoate dehydrogenase EC:1.4.1.12 # 2-amino-4-oxopentanoate thiolase (2.3.1.263) is heteromeric ortA 2-amino-4-oxopentanoate thiolase, alpha subunit curated:SwissProt::C1FW06 curated:SwissProt::E3PY98 ignore_other:2.3.1.263 ortB 2-amino-4-oxopentanoate thiolase, beta subunit curated:SwissProt::C1FW07 curated:SwissProt::E3PY97 ignore_other:2.3.1.263 # Or ornithine can be catabolized via D-ornithine, as in L-arginine # degradation XIV. A racemase converts L-ornithine to D-ornithine; an # aminomutase forms (2R,4S) 2,4-diaminopentanoate; a dehydrogenase # forms (2R)-2-amino-4-oxopentanoate, and a thiolase cleaves it to # D-alanine and acetyl-CoA. D-alanine could be oxidized to pyruvate or # perhaps secreted; this is not described here. ornithine-degradation: orr oraS oraE ord ortA ortB rocF arginase EC:3.5.3.1 # Pathways I, VI, or VII begin with rocF (arginase), which forms ornithine and urea. (The urea might not be utilized, so urease is not described here.) They differ in how the ornithine is catabolized. all: arginine-transport rocF ornithine-degradation astB N-succinylarginine dihydrolase EC:3.5.3.23 # Pathway II begins with arginine succinyltransferase and ends with succinate and glutamate. # The succinate would then be activated to # succinyl-CoA to restart the cycle, or the glutamate # might be oxidized to succinyl-CoA; these # steps are not included here. all: arginine-transport arginine-succinyltransferase astB astC astD astE # Q5R145 is misannotated in BRENDA. adiA arginine decarboxylase (AdiA/SpeA) EC:4.1.1.19 ignore:BRENDA::Q5R145 speB agmatinase EC:3.5.3.11 # Pathway III begins with decarboxylation to agmatine by adiA, followed by hydrolysis to putrescine and urea. all: arginine-transport adiA speB putrescine-degradation # Q89413 is misannotated in BRENDA aguA agmatine deiminase EC:3.5.3.12 ignore:BRENDA::Q89413 aguB N-carbamoylputrescine hydrolase EC:3.5.1.53 ignore:BRENDA::Q89413 # Pathway IV begins with adiA and agmatine deiminase (aguA), which yields # N-carbamoylputrescine; this is hydrolyzed to putrescine and urea. all: arginine-transport adiA aguA aguB putrescine-degradation # Some diverged members of this family had been reannotated as arginine deiminases, # putatively involved in citrulline catabolism by the reverse reaction. # However, the reverse reaction is thermodynamically quite unfavorable; more likely, # these proteins have a different function arcA arginine deiminase EC:3.5.3.6 ignore:reanno::Phaeo:GFF1616 ignore:reanno::WCS417:GFF3434 ignore:reanno::pseudo3_N2E3:AO353_25635 # arcB forms carbamoyl-phosphate and ornithine arcB ornithine carbamoyltransferase EC:2.1.3.3 # arcC from P. aeruginosa (P13982) was studied both biochemically and genetically # and linked to sequence by PMID:2537202 arcC carbamate kinase EC:2.7.2.2 uniprot:P13982 # Pathway V begins with arginine deiminase (arcA), forming citrulline, and # and a carbamoyltransferase # forms carbamoyl-phosphate and ornithine. # The carbamoyl-phosphate is consumed by carbamate kinase (in reverse, # forming ammonia and CO2 and ATP). all: arginine-transport arcA arcB arcC ornithine-degradation aroD L-arginine oxidase EC:1.4.3.25 aruI 2-ketoarginine decarboxylase EC:4.1.1.75 kauB 4-guanidinobutyraldehyde dehydrogenase EC:1.2.1.54 gbuA guanidinobutyrase EC:3.5.3.7 # Pathway VIII begins with arginine oxidase aroD, which forms 5-guanidino-2-oxopentanoate (2-ketoarginine); # this is converted to gamma-aminobutyrate (GABA). all: arginine-transport aroD aruI kauB gbuA GABA-degradation aruH L-arginine:pyruvate transaminase EC:2.6.1.84 # Pathway IX is similar to pathway VIII but the transaminase aruH forms the 5-guanidino-2-oxopentanoate. all: arginine-transport aruH aruI kauB gbuA GABA-degradation # arginine monooxygenase (EC 1.13.12.1) was linked to sequence by PMID:24218293, # but does not appear in any of the curated databases. # They showed that STRVN_2699 and STRVN_6565 are arginine monooxygenases; # these correspond to SMALA_2699 (A0A291SPZ4) and SMALA_6565 (A0A291T0Y3) arg-monooxygenase arginine 2-monooxygenase uniprot:A0A291SPZ4 uniprot:A0A291T0Y3 # This enzyme is not linked to sequence in MetaCyc (which gives it the # EC 3.5.1.4, for broad-specificity amidases). PMID:24218293 showed # that STRVN_6564 (SMALA_6564,A0A291T0X0) and _7510 (A0A291T3M3) # perform this reaction. And PMID:24752846 showed that A0A088BHP3 # (azl13, see genbank KF772886.1) performs this reaction. (It is # annotated in BRENDA as an amidase.) gbamidase guanidinobutyramidase uniprot:A0A291T0X0 uniprot:A0A291T3M3 curated:BRENDA::A0A088BHP3 # Pathway X involves # arginine 2-monooxygenase (decarboxylating), forming 4-guanidinobutyramide, # and an amidase, forming 4-guanidinobutyrate, which is consumed as # in pathway VIII or IX. all: arginine-transport arg-monooxygenase gbamidase kauB gbuA GABA-degradation
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
Otherwise, a candidate is "medium confidence" if either:
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory