Definition of L-arginine catabolism
As rules and steps, or see full text
Rules
Overview: Arginine utilization in GapMind is based on MetaCyc pathways L-arginine degradation I via arginase (link); II via arginine succinyltransferase (link), III via arginine decarboxylase and agmatinase (link), IV via arginine decarboxylase and agmatine deiminase (link), V via arginine deiminase (link), VI (arginase 2, link), VII (arginase 3, link), VIII via arginase oxidase (link), IX via arginine:pyruvate transaminase (link), X via arginine monooxygenase (link), XIII via proline (link), and XIV via D-ornithine (link). Common intermediates are L-ornithine or L-proline. GapMind does not include pathways XI (link), which is poorly understood, or XII (link), which is not reported in prokaryotes.
- all:
- arginine-transport, rocF and ornithine-degradation
- or arginine-transport, arginine-succinyltransferase, astB, astC, astD and astE
- or arginine-transport, adiA, speB and putrescine-degradation
- or arginine-transport, adiA, aguA, aguB and putrescine-degradation
- or arginine-transport, arcA, arcB, arcC and ornithine-degradation
- or arginine-transport, aroD, aruI, kauB, gbuA and GABA-degradation
- or arginine-transport, aruH, aruI, kauB, gbuA and GABA-degradation
- or arginine-transport, arg-monooxygenase, gbamidase, kauB, gbuA and GABA-degradation
- Comment: 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. 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. Pathway III begins with decarboxylation to agmatine by adiA, followed by hydrolysis to putrescine and urea. Pathway IV begins with adiA and agmatine deiminase (aguA), which yields N-carbamoylputrescine; this is hydrolyzed to putrescine and urea. 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). Pathway VIII begins with arginine oxidase aroD, which forms 5-guanidino-2-oxopentanoate (2-ketoarginine); this is converted to gamma-aminobutyrate (GABA). Pathway IX is similar to pathway VIII but the transaminase aruH forms the 5-guanidino-2-oxopentanoate. 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.
- ornithine-degradation:
- aruF, aruG, astC, astD and astE
- or rocD and rocA
- or rocD, PRO3 and proline-degradation
- or ocd and proline-degradation
- or odc and putrescine-degradation
- or orr, oraS, oraE, ord, ortA and ortB
- Comment: 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). 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. Or 1-pyrroline-5-carboxylate can be reduced to proline by PRO3, as in L-arginine degradation VI. Alternatively, ornithine can be converted directly to proline by ornithine cyclodeaminase (ocd). Or ornithine can be decarboxylated to putrescine by odc (link). 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.
- arginine-succinyltransferase:
- proline-degradation:
- put1 and putA
- or prdF, D-proline-reductase and 5-aminovalerate-degradation
- Comment: In pathway I, proline dehydrogenase (put1) forms (S)-1-pyrroline-5-carboxylate, which spontaneously hydrates to L-glutamate 5-semialdehyde, and a dehydrogenase (putA) to glutamate. Glutamate can be transaminated to 2-oxoglutarate, which is an intermediate in central metabolism (not represented). In pathway II, proline racemase (prdF) forms D-proline, and a reductase forms 5-aminovalerate.
- D-proline-reductase: prdA, prdB and prdC
- Comment: D-proline reductase includes components PrdA and PrdB and electron transfer protein PrdC
- 5-aminovalerate-degradation: davT, davD and glutarate-degradation
- Comment: 5-aminovalerate is an intermediate in L-lysine degradation (link, link). It is transaminated to glutarate semialdehyde and oxidized to glutarate. (A fermentative pathway via 5-hydroxyvalerate has also been reported, but does not seem to be fully linked to sequence; see pathway 5 of PMID:11759672.)
- glutarate-degradation:
- glaH and lhgD
- or gcdG and glutaryl-CoA-degradation
- Comment: Glutarate is an intermediate in L-lysine degradation. As part of MetaCyc pathway L-lysine degradation I (link), gluratate is hydroxylated to L-2-hydroxyglutarate (also known as (S)-2-hydroxyglutarate) by a 2-oxoglutarate-dependent oxidase. This reaction releases succinate (a TCA cycle intermediate) and CO2. A dehydrogenase then oxidizes to L-2-hydroxyglutarate to regenerate 2-oxoglutarate. Alternatively, as part of pathway IV (link), glutarate can be activated to glutaryl-CoA by a CoA-transferase. Glutaryl-CoA degradation (link) involves glutaryl-CoA dehydrogenase (decarboxylating) to crotonyl-CoA (trans-but-2-enoyl-CoA), hydration to (S)-hydroxybutanoyl-CoA, oxidization to acetoacetyl-CoA, and cleavage by a C-acetyltransferase to two acetyl-CoA.
- glutaryl-CoA-degradation: gcdH, ech, fadB and atoB
- Comment: In MetaCyc pathway glutaryl-CoA degradation (link), glutaryl-CoA is oxidized to (E)-glutaconyl-CoA and oxidatively decarboxylated to crotonyl-CoA (both by the same enzyme), hydrated to 3-hydroxybutanoyl-CoA, oxidized to acetoacetyl-CoA, and cleaved to two acetyl-CoA.
- GABA-degradation: gabT and gabD
- Comment: GABA (4-aminobutanoate) is consumed by an aminotransferase (known as gabT or puuE), which forms succinate semialdehyde, and dehydrogenase gabD, which forms succinate.
- putrescine-degradation: putrescine-to-GABA and GABA-degradation
- Comment: Gamma-aminobutyrate is a common intermediate.
- putrescine-to-GABA:
- patA and patD
- or puuA, puuB, puuC and puuD
- or puo and patD
- Comment: In pathway I or pathway V, putrescine aminotransferase (patA or spuC) forms 4-aminobutanal, and dehydrogenase patD forms GABA. In pathway II, putrescine is converted to GABA with glutamylated intermedates: puuA forms gamma-glutamyl-putrescine, an oxidase forms 4-(gamma-glutaminylamino)butanal, a dehydrogenase forms 4-(gamma-glutamylamino)butanoate, and a hydrolase releases glutamate and GABA. As part of pathway IV, putrescine oxidase (puo) forms 4-aminobutanal, which is probably converted to GABA by dehydrogenase patD.
- arginine-transport:
Steps
artJ: L-arginine ABC transporter, periplasmic substrate-binding component ArtJ/HisJ/ArtI/AotJ/ArgT
- Curated sequence AO353_03055: ABC transporter for L-Arginine and L-Citrulline, periplasmic substrate-binding component
- Curated sequence CH_002541: arginine ABC transporter, periplasmic arginine-binding protein ArtJ. ABC transporter arginine-binding protein 1. ArtJ aka B0860, component of Arginine porter. L-arginine ABC transporter periplasmic binding protein (EC 7.4.2.1). L-arginine ABC transporter periplasmic binding protein (EC 7.4.2.1)
- Curated sequence CH_003045: lysine/arginine/ornithine ABC transporter, periplasmic lysine/arginine/ornithine-binding protein ArgT. Lysine/arginine/ornithine-binding periplasmic protein; LAO-binding protein
- Curated sequence CH_014295: histidine ABC transporter, periplasmic histidine-binding protein HisJ. Histidine-binding periplasmic protein, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. histidine ABC transporter periplasmic binding protein (EC 7.4.2.1)
- Curated sequence P30859: Putative ABC transporter arginine-binding protein 2. ArtI aka B0863, component of Arginine porter
- Curated sequence O50181: AotJ aka PA0888, component of Arginine/ornithine (but not lysine) porter
- Curated sequence P09551: ArgT aka B2310, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter periplasmic binding protein (EC 7.4.2.1)
- Curated sequence Q9HU31: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter periplasmic binding protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
- Curated sequence BPHYT_RS07735: ABC transporter for L-Arginine, periplasmic substrate-binding component
- Curated sequence GFF4245: ABC transporter for L-Arginine, substrate-binding component
- Curated sequence Pf1N1B4_3431: ABC transporter for L-Arginine and L-Citrulline, periplasmic substrate-binding component
- Curated sequence AO356_18700: L-Arginine ABC transporter, periplasmic substrate-binding component
- Curated sequence Pf6N2E2_5660: L-Arginine ABC transporter, periplasmic substrate-binding component
- Ignore hits to CH_018185 when looking for 'other' hits (histidine ABC transporter, periplasmic histidine-binding protein HisJ. Histidine-binding periplasmic protein; HBP)
- Ignore hits to AO356_09900 when looking for 'other' hits (ABC transporter for L-Lysine, periplasmic substrate-binding component)
- Ignore hits to Pf6N2E2_2958 when looking for 'other' hits (ABC transporter for L-Lysine, periplasmic substrate-binding component)
- Ignore hits to AO356_05495 when looking for 'other' hits (ABC transporter for L-Lysine, periplasmic substrate-binding component)
- UniProt sequence E4PNW5: SubName: Full=Extracellular solute-binding protein, family 3 {ECO:0000313|EMBL:ADP98795.1};
- Comment: 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 (ARTJ_CHLTR, 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.
- Total: 14 characterized proteins
artM: L-arginine ABC transporter, permease component 1 (ArtM/HisM/AotM)
- Curated sequence P0A2I7: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM aka STM2352, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
- Curated sequence P0AEU3: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisM (EC 7.4.2.1)
- Curated sequence O50183: AotP aka AotM aka PA0890, component of Arginine/ornithine (but not lysine) porter
- Curated sequence Q9HU29: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter membrane protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
- Curated sequence BPHYT_RS07680: ABC transporter for L-Arginine, permease component 1
- Curated sequence GFF4243: ABC transporter for L-Arginine, permease component 2
- Curated sequence Pf1N1B4_3433: ABC transporter for L-Arginine and L-Citrulline, permease component 2
- Curated sequence AO353_03045: ABC transporter for L-Arginine and L-Citrulline, permease component 1
- Curated sequence AO356_18710: L-Arginine ABC transporter, permease component 1
- Curated sequence Pf6N2E2_5662: L-Arginine ABC transporter, permease protein AotM
- Curated sequence P0AE30: Arginine ABC transporter permease protein ArtM. Arginine transport system permease protein ArtM aka B0861, component of Arginine porter. L-arginine ABC transporter membrane subunit ArtM (EC 7.4.2.1). L-arginine ABC transporter membrane subunit ArtM (EC 7.4.2.1)
- Ignore hits to AO356_09910 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 2)
- Ignore hits to Pf6N2E2_2960 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 2)
- Ignore hits to AO356_05505 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 2)
- Comment: 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).
- Total: 11 characterized proteins
artP: L-arginine ABC transporter, ATPase component ArtP/HisP/AotP/BgtA
- Curated sequence CH_003210: histidine transport ATP-binding protein hisP. Histidine transport ATP-binding protein HisP, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, ATP binding subunit (EC 7.4.2.1)
- Curated sequence P02915: Histidine transport ATP-binding protein HisP. histidine transport atp-binding protein hisp. HisP aka STM2351, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
- Curated sequence P0AAF6: Arginine transport ATP-binding protein ArtP; EC 7.4.2.-. Arginine transport ATP-binding protein ArtP aka B0864, component of Arginine porter. L-arginine ABC transporter ATP binding subunit (EC 7.4.2.1). L-arginine ABC transporter ATP binding subunit (EC 7.4.2.1)
- Curated sequence P54537: Arginine transport ATP-binding protein ArtM
- Curated sequence O30506: AotP aka PA0892, component of Arginine/ornithine (but not lysine) porter
- Curated sequence P73721: BgtA aka SLR1735, component of Arginine/lysine/histidine/glutamine porter
- Curated sequence Q9HU32: Probable ATP-binding component of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
- Curated sequence BPHYT_RS07685: ABC transporter for L-Arginine, putative ATPase component
- Curated sequence Pf1N1B4_3435: ABC transporter for L-Arginine and L-Citrulline, ATPase component
- Curated sequence AO353_03040: ABC transporter for L-Arginine and L-Citrulline, ATPase component
- Curated sequence AO356_18715: L-Arginine ABC transporter, ATPase component
- Curated sequence Pf6N2E2_5663: L-Arginine ABC transporter, ATPase component
- Ignore hits to AO356_09895 when looking for 'other' hits (ABC transporter for L-Lysine, ATPase component)
- Ignore hits to AO356_05515 when looking for 'other' hits (ABC transporter for L-Lysine, ATPase component)
- Ignore hits to Pf6N2E2_2962 when looking for 'other' hits (ABC transporter for L-Lysine, ATPase component)
- Comment: Ignore closely related lysine transporters from P. fluorescens (which may well transport arginine; AO356_09895 has a subtle defect in arginine utilization)
- Total: 12 characterized proteins
artQ: L-arginine ABC transporter, permease component 2 (ArtQ/HisQ/AotQ)
- Curated sequence Q9HU30: Probable permease of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
- Curated sequence CH_107317: arginine/ornithine transport protein. AotQ, component of Arginine/ornithine (but not lysine) porter
- Curated sequence P0A2I9: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ aka STM2353, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
- Curated sequence P0AE34: Arginine ABC transporter permease protein ArtQ. Arginine transport system permease protein ArtQ aka B0862, component of Arginine porter. L-arginine ABC transporter membrane subunit ArtQ (EC 7.4.2.1). L-arginine ABC transporter membrane subunit ArtQ (EC 7.4.2.1)
- Curated sequence P52094: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisQ (EC 7.4.2.1)
- Curated sequence BPHYT_RS07675: ABC transporter for L-Arginine, permease component 2
- Curated sequence GFF4244: ABC transporter for L-Arginine, permease component 1
- Curated sequence Pf1N1B4_3432: ABC transporter for L-Arginine and L-Citrulline, permease component 1
- Curated sequence AO353_03050: ABC transporter for L-Arginine and L-Citrulline, permease component 2
- Curated sequence AO356_18705: L-Arginine ABC transporter, permease component 2
- Curated sequence Pf6N2E2_5661: L-Arginine ABC transporter, permease protein AotQ
- Ignore hits to AO356_09905 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 1)
- Ignore hits to Pf6N2E2_2959 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 1)
- Ignore hits to AO356_05500 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 1)
- Comment: Ignore closely related lysine transporters in P. fluorescens (which may well transport arginine; AO356_09905 has a subtle defect in arginine utilization)
- Total: 11 characterized proteins
bgtB: L-arginine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
- Curated sequence P73544: BgtB aka GLNH aka SLL1270, component of Arginine/lysine/histidine/glutamine porter
- Curated sequence Q8YSA2: Basic amino acid uptake transporter, BgtAB
- Comment: 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.)
- Total: 2 characterized proteins
braC: ABC transporter for glutamate, histidine, arginine, and other amino acids, substrate-binding component BraC
- Curated sequence Q9L3M3: BraC, component of General L- (and D-)amino acid uptake porter (transports acidic, basic, polar, semipolar and hydrophobic amino acids). The amino and carboxyl groups do not need to be α since γ-aminobutyric acid (GABA) is a substrate. The system may function with additional binding proteins since L-alanine uptake is not dependent on BraC
- Comment: In Rhizobium leguminosarum, a broad-specificity amino acid ABC transporter is known as braCDEFG. (A homologous system from Pseudomonas is thought to have a narrower substrate range.)
- Total: 1 characterized proteins
braD: ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 1 (BraD)
- UniProt sequence Q1MCU0: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09240.1};
- Total: 1 characterized proteins
braE: ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 2 (BraE)
- UniProt sequence Q1MCU1: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09239.1};
- Total: 1 characterized proteins
braF: ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 1 (BraF)
- UniProt sequence Q1MCU2: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09238.1};
- Total: 1 characterized proteins
braG: ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 2 (BraG)
- UniProt sequence Q1MCU3: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09237.1};
- Total: 1 characterized proteins
rocE: L-arginine permease
- Curated sequence CH_091412: uncharacterized amino-acid permease C869.11. The basic amino acid (canavanine sensitivity) transporter, Cat1
- Curated sequence CH_091699: arginine permease. Arginine permease CAN1; Canavanine resistance protein 1. Arginine permease
- Curated sequence A0A1D8PPG4: Probable lysine/arginine permease CAN3; Basic amino acids permease CAN3
- Curated sequence A0A1D8PPI5: Lysine/arginine permease CAN1; Basic amino acids permease CAN1
- Curated sequence P39137: Amino-acid permease RocE. L-Arginine permease, RocE
- Curated sequence Q59WB3: S-adenosylmethionine permease GAP4; SAM permease; Amino-acid permease GAP4. potential general amino acid permease. Arginine transporter, GAP4
- Curated sequence Q59WU0: Probable lysine/arginine permease CAN2; Basic amino acids permease CAN2
- Curated sequence Q5AG77: Amino-acid permease GAP1. general amino acid permease. Amino acid permease, GAP1. Transports Arg, Met, Leu and Phe
- Curated sequence P43059: The high affinity basic amino acid (Arg, Lys, His) transporter, Can1
- Total: 9 characterized proteins
AAP3: L-arginine transporter AAP3
- Curated sequence Q86G79: ABC-type polar-amino-acid transporter (EC 7.4.2.1). Arginine-specific transporter, AAP3 (KM (Arg) = 2μM)
- Total: 1 characterized proteins
CAT1: L-arginine transporter CAT1
- Curated sequence CH_091324: high affinity cationic amino acid transporter 1. High affinity cationic amino acid transporter 1; CAT-1; CAT1; Ecotropic retroviral leukemia receptor; Ecotropic retrovirus receptor; ERR; Solute carrier family 7 member 1; System Y+ basic amino acid transporter. System Y+ high affinity basic amino acid transporter (CAT1) (ecotropic retrovival leukemia virus receptor (ERR)) (transports arginine, lysine and ornithine; Na+-independent)
- Total: 1 characterized proteins
Can1: L-arginine transporter Can1
patA: putrescine aminotransferase (PatA/SpuC)
- Curated proteins or TIGRFams with EC 2.6.1.82
- Curated sequence MONOMER-17: putrescine-pyruvate transaminase (EC 2.6.1.113). Putrescine--pyruvate aminotransferase; PATase; Putrescine--pyruvate transaminase; EC 2.6.1.113. putrescine aminotransferase (EC 2.6.1.113)
- Curated proteins or TIGRFams with EC 2.6.1.113
- Ignore hits to items matching 2.6.1.19 when looking for 'other' hits
- Comment: Since patA and putrescine-pyruvate transaminase (spuC) perform similar reactions and produce gamma-aminobutyraldehyde (4-aminobutanal), they are listed together. Many close homologs of patA are GABA aminotransferases (EC 2.6.1.19), so ignore those.
- Total: 1 HMMs and 2 characterized proteins
patD: gamma-aminobutyraldehyde dehydrogenase
puuA: glutamate-putrescine ligase
puuB: gamma-glutamylputrescine oxidase
puuC: gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.99
- Curated sequence MONOMER-11560: 4-guanidinobutyraldehyde dehydrogenase (EC 1.2.1.54)
- Curated sequence PfGW456L13_805: gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase (EC 1.2.1.54)
- Curated sequence Pf6N2E2_4383: gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase (EC 1.2.1.54)
- Curated sequence AO356_12580: gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase (EC 1.2.1.54)
- Curated sequence GFF5420: gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase (EC 1.2.1.54)
- Comment: The putative kauB (4-guanidinobutyraldehyde dehydrogenase) from P. putida (metacyc::MONOMER-11560) is included because it is closely related to P. aeruginosa kauB (PA5312), which acts on gamma-glutamyl-gamma-aminobutyraldehyde as well (PMID:3141581). Some other P. fluorescens kauB-type proteins seem to be acting in this pathway but were annotated with EC 1.2.1.54 instead, so these were added manually.
- Total: 6 characterized proteins
puuD: gamma-glutamyl-gamma-aminobutyrate hydrolase
puo: putrescine oxidase
gabT: gamma-aminobutyrate transaminase
- Curated proteins or TIGRFams with EC 2.6.1.19
- Curated proteins or TIGRFams with EC 2.6.1.96
- UniProt sequence A1S8Y2: SubName: Full=4-aminobutyrate aminotransferase {ECO:0000313|EMBL:ABM00839.1}; EC=2.6.1.19 {ECO:0000313|EMBL:ABM00839.1};
- Comment: Sama_2636 (A1S8Y2) was added because it is a transaminase involved in putrescine utilization
- Total: 2 HMMs and 28 characterized proteins
gabD: succinate semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.79
- Curated proteins or TIGRFams with EC 1.2.1.24
- Curated proteins or TIGRFams with EC 1.2.1.16
- Ignore hits to Q8BUF0 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NAD+) (EC 1.2.1.24))
- Ignore hits to items matching 1.2.1.20 when looking for 'other' hits
- Ignore hits to items matching 1.2.1.3 when looking for 'other' hits
- Ignore hits to Q9I6M5 when looking for 'other' hits (Glutarate-semialdehyde dehydrogenase; EC 1.2.1.-. glutarate semialdehyde dehydrogenase)
- Comment: This may be either NADH or NADPH dependent, forming succinate in either case. Close homologs in Pseudomonas or Klebsiella are annotated as glutarate-semialdehyde dehydrogenases (1.2.1.20) or aldehyde dehydrogenases (1.2.1.3); Q9I6M5 is annotated as glutarate-semialdehyde dehydrogenase but with no EC number. Q8BUF0 appears to be misannotated in BRENDA.
- Total: 37 characterized proteins
atoB: acetyl-CoA C-acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.9
- Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
- Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
- Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
- Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
- Total: 36 characterized proteins
gcdH: glutaryl-CoA dehydrogenase
ech: (S)-3-hydroxybutanoyl-CoA hydro-lyase
- Curated proteins or TIGRFams with EC 4.2.1.150
- Ignore hits to Q97MS7 when looking for 'other' hits (short-chain-enoyl-CoA hydratase (EC 4.2.1.150))
- Curated sequence BPHYT_RS17335: trans-2,3-dehydroadipyl-CoA hydratase (EC 4.2.1.17)
- Curated sequence GFF2389: Enoyl-CoA hydratase [valine degradation] (EC 4.2.1.17)
- Ignore hits to items matching 4.2.1.17 when looking for 'other' hits
- Comment: Psest_2437 (GFF2389) is the enoyl-CoA hydrotase for both isoleucine and valine degradation, which implies that (S)-3-hydroxybutanoyl-CoA is a substrate. Q97MS7 is misannotated in BRENDA. BPHYT_RS17335 was misannotated as paaF; it is very similar to the ech H16_A3307, which is a different explanation for its role in phenylacetate utilization. Short-chain enoyl-CoA hydratases are sometimes given EC 4.2.1.17 instead, so those are ignored.
- Total: 8 characterized proteins
fadB: (S)-3-hydroxybutanoyl-CoA dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.35
- Ignore hits to GFF1550 when looking for 'other' hits (Enoyl-CoA hydratase (EC 4.2.1.17))
- Comment: HP15_1512 (GFF1550) is annotated as enoyl-CoA hydratase but likely does this as well
- Total: 36 characterized proteins
glaH: glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
lhgD: L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)
- Curated proteins or TIGRFams with EC 1.1.5.13
- Curated sequence G1G01-3089-MONOMER: (S)-2-hydroxyglutarate oxidase
- Curated proteins or TIGRFams with EC 1.1.99.2
- Comment: As discussed in the MetaCyc page for lhgO (G1G01-3089-MONOMER), there is some controversy as to whether the E. coli enzyme (lhgD) uses quinone or oxygen as its acceptor; the Pseudomonas protein (G1G01-3089-MONOMER) does use oxygen.
- Total: 4 characterized proteins
gcdG: succinyl-CoA:glutarate CoA-transferase
davT: 5-aminovalerate aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.48
- Ignore hits to MONOMER-11537 when looking for 'other' hits (4-aminobutyrate transaminase subunit (EC 2.6.1.19))
- Ignore hits to Q0K2K2 when looking for 'other' hits (4-aminobutyrate-2-oxoglutarate transaminase (EC 2.6.1.19). 4-aminobutyrate aminotransferase monomer (EC 2.6.1.19))
- Comment: Ignore some very-similar 4-aminobutyrate transaminases
- Total: 6 characterized proteins
davD: glutarate semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.20
- Ignore hits to AO353_11505 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (EC 1.2.1.16))
- Ignore hits to MONOMER-15736 when looking for 'other' hits (NAD(P)-dependent succinate-semialdehyde dehydrogenase (EC 1.2.1.16))
- Curated sequence Q9I6M5: Glutarate-semialdehyde dehydrogenase; EC 1.2.1.-. glutarate semialdehyde dehydrogenase
- Ignore hits to P25526 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NADP+) (EC 1.2.1.79). succinate-semialdehyde dehydrogenase [NAD(P)+]; EC 1.2.1.16. Succinate-semialdehyde dehydrogenase [NADP(+)] GabD; SSDH; Glutarate-semialdehyde dehydrogenase; EC 1.2.1.79; EC 1.2.1.-. succinate-semialdehyde dehydrogenase (NADP+) GabD (EC 1.2.1.79). succinate-semialdehyde dehydrogenase (NADP+) GabD (EC 1.2.1.79))
- Ignore hits to MONOMER-20455 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NAD+) (EC 1.2.1.24))
- Ignore hits to 200453 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NADP+) [EC: 1.2.1.16])
- Comment: Ignore some very-similar succinate-semialdehyde dehydrogenases
- Total: 3 characterized proteins
prdA: D-proline reductase, prdA component
- Curated sequence CH_013105: D-proline reductase, PrdA proprotein; EC 1.21.4.1
- Curated sequence Q9Z4P6: D-proline reductase proprotein PrdA; EC 1.21.4.1. proprotein PrdA
- Ignore hits to items matching 1.21.4.1 when looking for 'other' hits
- Total: 2 characterized proteins
prdB: D-proline reductase, prdB component
- Curated sequence Q17ZY6: D-proline reductase (EC 1.21.4.1)
- Curated sequence CH_013103: D-proline reductase, PrdB subunit, selenocysteine-containing; EC 1.21.4.1. D-proline reductase subunit gamma; D-proline reductase 26 kDa subunit; EC 1.21.4.1. 26-kDa subunit
- Ignore hits to items matching 1.21.4.1 when looking for 'other' hits
- Total: 2 characterized proteins
prdC: D-proline reductase, electron transfer component PrdC
put1: proline dehydrogenase
putA: L-glutamate 5-semialdeyde dehydrogenase
prdF: proline racemase
- Curated proteins or TIGRFams with EC 5.1.1.4
- Ignore hits to Q4D480 when looking for 'other' hits (proline racemase (EC 5.1.1.4))
- Comment: Q4D480 is misannotated in BRENDA.
- Total: 8 characterized proteins
aruF: ornithine/arginine N-succinyltransferase subunit AruAI (AruF)
aruG: ornithine/arginine N-succinyltransferase subunit AruAII (AruG)
astA: arginine N-succinyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.109
- Ignore hits to CH_107315 when looking for 'other' hits (arginine N-succinyltransferase; EC 2.3.1.109)
- Ignore hits to P80358 when looking for 'other' hits (arginine N-succinyltransferase (EC 2.3.1.109). arginine N-succinyltransferase, beta subunit)
- Comment: The other known arginine N-succinyltransferases have just one subunit and are not known to be active on ornithine.
- Total: 2 HMMs and 6 characterized proteins
astC: succinylornithine transaminase
- Curated proteins or TIGRFams with EC 2.6.1.81
- Curated sequence GFF3099: acetylornithine/N-succinyldiaminopimelate aminotransferase [EC:2.6.1.11 2.6.1.17]
- Comment: 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)
- Total: 1 HMMs and 8 characterized proteins
astD: succinylglutamate semialdehyde dehydrogenase
astE: succinylglutamate desuccinylase
rocD: ornithine aminotransferase
rocA: 1-pyrroline-5-carboxylate dehydrogenase
PRO3: pyrroline-5-carboxylate reductase
ocd: ornithine cyclodeaminase
odc: L-ornithine decarboxylase
orr: ornithine racemase
oraS: D-ornithine 4,5-aminomutase, alpha (S) subunit
- Curated sequence E3PY96: D-ornithine 4,5-aminomutase subunit alpha; D-ornithine aminomutase S component; OAM-S; EC 5.4.3.5. D-ornithine 4,5-aminomutase (subunit 1/2) (EC 5.4.3.5). D-ornithine aminomutase component S subunit (EC 5.4.3.5)
- Ignore hits to items matching 5.4.3.5 when looking for 'other' hits
- Comment: D-ornithine aminomutase (5.4.3.5) is heteromeric
- Total: 1 characterized proteins
oraE: D-ornithine 4,5-aminomutase, beta (E) subunit
- Curated sequence E3PY95: D-ornithine 4,5-aminomutase subunit beta; D-ornithine aminomutase E component; OAM-E; EC 5.4.3.5. D-ornithine 4,5-aminomutase (EC 5.4.3.5). D-ornithine aminomutase component E subunit (EC 5.4.3.5)
- Ignore hits to items matching 5.4.3.5 when looking for 'other' hits
- Total: 1 characterized proteins
ord: 2,4-diaminopentanoate dehydrogenase
ortA: 2-amino-4-oxopentanoate thiolase, alpha subunit
- Curated sequence C1FW06: 2-amino-4-ketopentanoate thiolase alpha subunit; AKP thiolase; AKPT; EC 2.3.1.263. 2-amino-4-oxopentanoate thiolase (subunit 1/2) (EC 2.3.1.263). AKP thiolase α subunit (EC 2.3.1.263)
- Curated sequence E3PY98: 2-amino-4-ketopentanoate thiolase alpha subunit; AKP thiolase; AKPT; EC 2.3.1.263
- Ignore hits to items matching 2.3.1.263 when looking for 'other' hits
- Comment: 2-amino-4-oxopentanoate thiolase (2.3.1.263) is heteromeric
- Total: 2 characterized proteins
ortB: 2-amino-4-oxopentanoate thiolase, beta subunit
- Curated sequence C1FW07: 2-amino-4-ketopentanoate thiolase beta subunit; AKP thiolase; AKPT; EC 2.3.1.263. 2-amino-4-oxopentanoate thiolase (subunit 2/2) (EC 2.3.1.263). AKP thiolase β subunit (EC 2.3.1.263)
- Curated sequence E3PY97: 2-amino-4-ketopentanoate thiolase beta subunit; AKP thiolase; AKPT; EC 2.3.1.263
- Ignore hits to items matching 2.3.1.263 when looking for 'other' hits
- Total: 2 characterized proteins
rocF: arginase
astB: N-succinylarginine dihydrolase
adiA: arginine decarboxylase (AdiA/SpeA)
speB: agmatinase
aguA: agmatine deiminase
aguB: N-carbamoylputrescine hydrolase
arcA: arginine deiminase
- Curated proteins or TIGRFams with EC 3.5.3.6
- Ignore hits to GFF1616 when looking for 'other' hits (arginine deiminase (EC 3.5.3.6))
- Ignore hits to GFF3434 when looking for 'other' hits (arginine deiminase (EC 3.5.3.6))
- Ignore hits to AO353_25635 when looking for 'other' hits (arginine deiminase (EC 3.5.3.6))
- Comment: 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
- Total: 1 HMMs and 10 characterized proteins
arcB: ornithine carbamoyltransferase
arcC: carbamate kinase
aroD: L-arginine oxidase
aruI: 2-ketoarginine decarboxylase
kauB: 4-guanidinobutyraldehyde dehydrogenase
gbuA: guanidinobutyrase
aruH: L-arginine:pyruvate transaminase
arg-monooxygenase: arginine 2-monooxygenase
- UniProt sequence A0A291SPZ4: SubName: Full=Arginine 2-monooxygenase (Decarboxylating) {ECO:0000313|EMBL:ATL82933.1}; EC=1.13.12.3 {ECO:0000313|EMBL:ATL82933.1}; SubName: Full=FAD-dependent oxidoreductase {ECO:0000313|EMBL:QDL72858.1};
- UniProt sequence A0A291T0Y3: SubName: Full=Arginine 2-monooxygenase (Decarboxylating) {ECO:0000313|EMBL:ATL86793.1}; EC=1.13.12.3 {ECO:0000313|EMBL:ATL86793.1}; SubName: Full=FAD-dependent oxidoreductase {ECO:0000313|EMBL:QDL69688.1};
- Comment: 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)
- Total: 2 characterized proteins
gbamidase: guanidinobutyramidase
- UniProt sequence A0A291T0X0: SubName: Full=4-guanidinobutyramide hydrolase {ECO:0000313|EMBL:ATL86792.1}; SubName: Full=Carbon-nitrogen hydrolase {ECO:0000313|EMBL:QDL69689.1};
- UniProt sequence A0A291T3M3: SubName: Full=Putative 4-guanidinobutyryl amide hydrolase {ECO:0000313|EMBL:ATL87726.1};
- Curated sequence A0A088BHP3: aryl-acylamidase (EC 3.5.1.13); amidase (EC 3.5.1.4)
- Comment: 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.)
- Total: 3 characterized proteins
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About GapMind
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:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
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:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
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