Definition of L-leucine catabolism
As rules and steps, or see full text
Rules
Overview: Leucine degradation in GapMind is based on MetaCyc pathway L-leucine degradation I, via branched alpha-keto acid dehydrogenase (link). Other pathways for are not included here because they are not linked to sequence (link) or do not result in carbon incorporation.
- all: leucine-transport, ilvE, BKD, liuA, liuB, liuD, liuC, liuE and acetoacetate-degradation
- Comment: After transamination to 4-methyl-2-oxopentanoate by ilvE, kbd oxidatively decarboxylates it to isovaleryl-CoA (also known as 3-methylbutanoyl-CoA), liuA oxidizes it to 3-methylcrotonyl-CoA, liuBD carboxylates it to 3-methylglutaconyl-CoA, liuC hydrates it to hydroxymethylglutaryl-CoA, and liuE hydrolyzes it to acetoacetate and acetyl-CoA.
- acetoacetate-degradation: acetoacetate-activation and atoB
- Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
- acetoacetate-activation:
- atoA and atoD
- or aacS
- Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
- BKD:
- bkdA, bkdB, bkdC and lpd
- or vorA, vorB and vorC
- or ofoA and ofoB
- or ofo
- Comment: These decarboxylating dehydrogenases act on 4-methyl-2-oxopentanoate, 3-methyl-2-oxobutanoate (2-oxoisovalerate) and (S)-3-methyl-2-oxopentanoate and are known as the branched-chain alpha-ketoacid dehydrogenases. They can pass electrons to NAD (EC 1.2.1.25) or to ferredoxin (EC 1.2.7.7). The NAD-dependent enzyme is the sum of three activities: EC 1.2.4.4 (the 4-methyl-2-oxopentanoate dehydrogenase, with transfer to the lipopoyllysine residue of 2.3.1.168) which is itself heteromeric, with alpha and beta subunits; EC 2.3.1.168 (dihydrolipoyllysine-residue (3-methylbutanoyl)transferase); and EC 1.8.1.4 (dihydrolipoyl dehydrogenase, transferring electrons to NAD). The well-characterized ferredoxin-dependent enzymes have 3 subunits (vorABC) or 2 subunits (ofoAB). Genetic data identified a fused ferredoxin-dependent enzyme with just 1 subunit (ofo).
- leucine-transport:
Steps
livF: L-leucine ABC transporter, ATPase component 1 (LivF/BraG)
- Curated sequence CH_003736: high-affinity branched-chain amino acid ABC transporter, ATP-binding protein LivF. LivF aka B3454, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivF (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivF (EC 7.4.2.2)
- Curated sequence P21630: High-affinity branched-chain amino acid transport ATP-binding protein BraG, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q8DQH7: ABC transporter ATP-binding protein-branched chain amino acid transport, component of The branched chain hydrophobic amino acid transporter, LivJFGHM
- UniProt sequence Q1MCU3: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09237.1};
- UniProt sequence A0A165KC78: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15317.1};
- Comment: E. coli livFGHMJ or livFGHMK (livK and livJ are alternate SBPs); and livJFGHM from Streptococcus pneumoniae; and braCDEFG from Pseudomonas aeruginosa (braC is the SBP); and braDEFG/braC3 from R. leguminosarum; braC3 (RL3540; Q1MDE9) is a secondary SBP that transports leucine/isoleucine/valine/alanine (PMID:19597156); the proximal braC (Q9L3M3) is also thought to be involved in leucine transport (PMC135202); LivH/BraD = RL3750/Q1MCU0; LivM/BraE = RL3749/Q1MCU1; LivG/BraF = RL3748/Q1MCU2; LivF/BraG = RL3747/Q1MCU3; and in Acidovorax sp. GW101-3H11: LivF = Ac3H11_1692 (A0A165KC78), LivG = Ac3H11_1693 (A0A165KC86), LivJ = Ac3H11_2396 (A0A165KTD4; not near the other components, but strong phenotype on leucine and cofitness), LivH = Ac3H11_1695 (A0A165KC95), LivM = Ac3H11_1694 (A0A165KER0);
- Total: 5 characterized proteins
livG: L-leucine ABC transporter, ATPase component 2 (LivG/BraF)
- Curated sequence P0A9S7: High-affinity branched-chain amino acid transport ATP-binding protein LivG aka B3455, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivG (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivG (EC 7.4.2.2)
- Curated sequence P21629: High-affinity branched-chain amino acid transport ATP-binding protein BraF, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q8DQH8: ABC transporter ATP-binding protein-branched chain amino acid transport, component of The branched chain hydrophobic amino acid transporter, LivJFGHM
- UniProt sequence Q1MCU2: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09238.1};
- UniProt sequence A0A165KC86: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15318.1};
- Total: 5 characterized proteins
livJ: L-leucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
- Curated sequence P21175: Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein; LIVAT-BP; Leu/Ile/Val/Thr/Ala-binding protein. Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence CH_107418: leucine-specific-binding protein LivK. Livk aka B3458, component of Leucine; leucine/isoleucine/valine porter. L-leucine/L-phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2). L-leucine/L-phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2)
- Curated sequence P0AD96: Leu/Ile/Val-binding protein LivJ aka B3460 aka LIV-BP, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2)
- Curated sequence Q8DQI1: ABC transporter substrate-binding protein-branched chain amino acid transport, component of The branched chain hydrophobic amino acid transporter, LivJFGHM
- UniProt sequence Q1MDE9: SubName: Full=Solute-binding (Aliphatic amino acid) component of ABC transporter {ECO:0000313|EMBL:CAK09028.1};
- 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
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Total: 7 characterized proteins
livH: L-leucine ABC transporter, permease component 1 (LivH/BraD)
- Curated sequence P21627: High-affinity branched-chain amino acid transport system permease protein BraD, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q8DQI0: ABC transporter membrane-spanning permease-branched chain amino acid transport, component of The branched chain hydrophobic amino acid transporter, LivJFGHM
- Curated sequence LIVH-MONOMER: branched chain amino acid/phenylalanine ABC transporter membrane subunit LivH (EC 7.4.2.2). high-affinity branched-chain amino acid ABC transporter, permease protein LivH. High-affinity branched-chain amino acid transport system permease protein LivH aka B3457, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter membrane subunit LivH (EC 7.4.2.2)
- UniProt sequence Q1MCU0: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09240.1};
- UniProt sequence A0A165KC95: SubName: Full=ABC transporter permease {ECO:0000313|EMBL:KZT15319.1};
- Total: 5 characterized proteins
livM: L-leucine ABC transporter, permease component 2 (LivM/BraE)
- Curated sequence P22729: High-affinity branched-chain amino acid transport system permease protein LivM; LIV-I protein M. LivM aka B3456, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter membrane subunit LivM (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter membrane subunit LivM (EC 7.4.2.2)
- Curated sequence P21628: High-affinity branched-chain amino acid transport system permease protein BraE, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q8DQH9: ABC transporter membrane-spanning permease-branched chain amino acid transport, component of The branched chain hydrophobic amino acid transporter, LivJFGHM
- UniProt sequence Q1MCU1: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09239.1};
- UniProt sequence A0A165KER0: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15410.1};
- Comment: LivM from Streptococcus pneumoniae lacks an N-terminal domain of unknown function (DUF3382) that is found in E.coli and P. aeruginosa
- Total: 5 characterized proteins
natA: L-leucine ABC transporter, ATPase component 1 (NatA)
- Curated sequence Q55164: NatA aka BRAF aka SLR0467, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q7A2H0: NatA, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Comment: Synechocystis natABCDE and a related system in Anabaena (annotated with "leu" not leucine as the substrate)
- Total: 2 characterized proteins
natB: L-leucine ABC transporter, substrate-binding component NatB
- Curated sequence Q55387: NatB aka SLR0559, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YVY4: NatB, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 2 characterized proteins
natC: L-leucine ABC transporter, permease component 1 (NatC)
- Curated sequence P74455: NatC aka SLL0146, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YY08: NatC, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 2 characterized proteins
natD: L-leucine ABC transporter, permease component 2 (NatD)
- Curated sequence P74318: NatD aka LivH aka SLR0949, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YXD0: NatD, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 2 characterized proteins
natE: L-leucine ABC transporter, ATPase component 2 (NatE)
- Curated sequence P73650: NatE aka LivF aka SLR1881, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YT15: NatE, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 2 characterized proteins
aapJ: ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), substrate-binding component AapJ
- Curated sequence Q52812: AapJ, component of General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux)
- Ignore hits to SMc02118 when looking for 'other' hits (ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, periplasmic substrate-binding component)
- Total: 1 characterized proteins
aapQ: ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 1 (AapQ)
- Curated sequence Q52813: AapQ, component of General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux)
- Ignore hits to SMc02119 when looking for 'other' hits (ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, permease component 1)
- Total: 1 characterized proteins
aapM: ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 2 (AapM)
- Curated sequence Q52814: AapM, component of General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux)
- Ignore hits to SMc02120 when looking for 'other' hits (ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, permease component 2)
- Total: 1 characterized proteins
aapP: ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), ATPase component AapP
- Curated sequence Q52815: AapP, component of General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux)
- Ignore hits to SMc02121 when looking for 'other' hits (ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, ATPase component)
- Total: 1 characterized proteins
leuT: L-leucine:Na+ symporter LeuT
- Curated sequence O67854: The amino acid (leucine):2 Na+ symporter, LeuTAa (Yamashita et al., 2005). LeuT possesses two ion binding sites, NA1 and NA2, both highly specific for Na+ but with differing mechanisms of binding (Noskov and Roux, 2008). X-ray structures have been determined for LeuT in substrate-free outward-open and apo inward-open states
- Total: 1 characterized proteins
brnQ: L-leucine:Na+ symporter BrnQ/BraB
- Curated sequence P0AD99: Branched chain amino acid transporter 2 of 439 aas and 12 TMSs, BrnQ. branched chain amino acid transporter BrnQ. branched chain amino acid transporter BrnQ
- Curated sequence P19072: Branched chain amino acid: Na+ symporter
- Total: 2 characterized proteins
bcaP: L-leucine uptake transporter BcaP
- Curated sequence S6EX81: Branched chain amino acid (Leucine/isoleucine/valine) uptake transporter of 469 aas and 12 TMSs, BcaP or CitA
- Total: 1 characterized proteins
Bap2: L-leucine permease Bap2
- Curated sequence CH_091448: Leu/Val/Ile amino-acid permease. Leu/Val/Ile amino acid permease
- Curated sequence Q2VQZ4: Arbuscular mycorrhizal fungal proline:H+ symporter, AAP1 (binds and probably transports nonpolar, hydrophobic amino acids)
- Total: 2 characterized proteins
AAP1: L-leucine permease AAP1
- Curated sequence CH_091601: amino acid transporter. Amino acid permease 1; Amino acid transporter AAP1; Neutral amino acid transporter II. General amino acid permease 1, AAP1 (transports most neutral and acidic amino acids but not aspartate or the basic amino acids). amino acid permease 1
- Total: 1 characterized proteins
ilvE: L-leucine transaminase
- Curated proteins or TIGRFams with EC 2.6.1.6
- Curated proteins or TIGRFams with EC 2.6.1.42
- Comment: These enzymes transfer the amino group to 2-oxoglutarate to form glutamate; glutamate dehydrogenase (not included in the pathway definition) can then release the ammonia. Many other paths are possible but do not seem to be known (i.e., transfer to oxaloacetate followed by aspartate-ammonia lyase).
- Total: 2 HMMs and 47 characterized proteins
bkdA: branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit
- Curated sequence P12694: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4. branched-chain α-keto acid dehydrogenase E1 component α subunit (EC 1.2.4.4)
- Curated sequence Q72GU1: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence CH_121278: 2-oxoisovalerate dehydrogenase subunit alpha; EC 1.2.4.4
- Curated sequence O45924: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; EC 1.2.4.4
- Curated sequence P11178: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4
- Curated sequence P9WIS3: 3-methyl-2-oxobutanoate dehydrogenase subunit alpha; Branched-chain alpha-ketoacid dehydrogenase E1 component subunit alpha; BCKADH E1-alpha; EC 1.2.4.4
- Curated sequence Q5SLR4: 2-oxoisovalerate dehydrogenase subunit alpha; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDH E1-alpha; EC 1.2.4.4
- Curated sequence Q84JL2: 2-oxoisovalerate dehydrogenase subunit alpha 2, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4
- Curated sequence Q9LPL5: 2-oxoisovalerate dehydrogenase subunit alpha 1, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4
- Curated sequence SMc03201: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence PfGW456L13_3540: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence AO353_26635: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence AO356_22990: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence Pf6N2E2_481: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence MONOMER-11683: 2-keto-isovalerate dehydrogenase component α subunit (EC 1.2.4.4)
- Total: 15 characterized proteins
bkdB: branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit
- Curated sequence CH_121283: 2-oxoisovalerate dehydrogenase subunit beta; EC 1.2.4.4
- Curated sequence P21953: 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component beta chain; BCKDE1B; BCKDH E1-beta; EC 1.2.4.4. branched-chain α-keto acid dehydrogenase E1 component β subunit (EC 1.2.4.4)
- Curated sequence P9WIS1: 3-methyl-2-oxobutanoate dehydrogenase subunit beta; Branched-chain alpha-ketoacid dehydrogenase E1 component subunit beta; BCKADH E1-beta; EC 1.2.4.4
- Curated sequence Q5SLR3: 2-oxoisovalerate dehydrogenase subunit beta; Branched-chain alpha-keto acid dehydrogenase E1 component beta chain; BCKDH E1-beta; EC 1.2.4.4
- Curated sequence Q9LDY2: 2-oxoisovalerate dehydrogenase subunit beta 2, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component beta chain; BCKDE1B; BCKDH E1-beta; Protein DARK INDUCIBLE 4; EC 1.2.4.4
- Curated sequence MONOMER-11684: 2-keto-isovalerate dehydrogenase component β subunit (EC 1.2.4.4)
- Curated sequence SMc03202: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence GFF3430: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence PfGW456L13_3541: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence AO356_22985: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence Pf6N2E2_480: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (EC 1.2.4.4)
- Curated sequence Q9HIA4: branched-chain-2-oxoacid decarboxylase (subunit 2/2) (EC 4.1.1.72)
- Total: 12 characterized proteins
bkdC: branched-chain alpha-ketoacid dehydrogenase, E2 component
lpd: branched-chain alpha-ketoacid dehydrogenase, E3 component
vorA: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit VorA
- Curated sequence P80907: Ketoisovalerate oxidoreductase subunit VorA; VOR; 2-oxoisovalerate oxidoreductase alpha chain; 2-oxoisovalerate-ferredoxin oxidoreductase subunit alpha; EC 1.-.-.-
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Total: 1 characterized proteins
vorB: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit VorB
- Curated sequence P80908: Ketoisovalerate oxidoreductase subunit VorB; VOR; 2-oxoisovalerate ferredoxin reductase subunit beta; 2-oxoisovalerate oxidoreductase beta chain; EC 1.2.7.7
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Total: 1 characterized proteins
vorC: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, gamma subunit VorC
- Curated sequence P80909: Ketoisovalerate oxidoreductase subunit VorC; VOR; 2-oxoisovalerate ferredoxin reductase subunit gamma; 2-oxoisovalerate oxidoreductase gamma chain; EC 1.2.7.7
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Total: 1 characterized proteins
ofoA: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA
- Curated sequence P72578: 2-oxoacid:ferredoxin oxidoreductase subunit alpha; OFOR; EC 1.2.7.11. 2-oxoacid oxidoreductase (ferredoxin) (subunit 2/2) (EC 1.2.7.11). 2-oxoacid:ferredoxin oxidoreductase α subunit (EC 1.2.7.11; EC 1.2.7.1; EC 1.2.7.3; EC 1.2.7.7)
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Ignore hits to items matching 1.2.7.11 when looking for 'other' hits
- Comment: ofoAB is similar to low-specificity 2-oxoacid oxidoreductases (EC 1.2.7.11); it is generally not certain if these act on 4-methyl-2-oxopentanoate or not, but they probably do.
- Total: 1 characterized proteins
ofoB: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB
- Curated sequence P72579: 2-oxoacid:ferredoxin oxidoreductase subunit beta; OFOR; EC 1.2.7.11. 2-oxoacid oxidoreductase (ferredoxin) (subunit 1/2) (EC 1.2.7.11). 2-oxoacid:ferredoxin oxidoreductase β subunit (EC 1.2.7.11; EC 1.2.7.1; EC 1.2.7.3; EC 1.2.7.7)
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Ignore hits to items matching 1.2.7.11 when looking for 'other' hits
- Total: 1 characterized proteins
ofo: branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
- Curated sequence RR42_RS19540: 3-methyl-2-oxobutanoate:ferredoxin oxidoreductase (EC 1.2.7.7)
- Curated sequence GFF3452: branched-chain ketoacid ferredoxin reductase (EC 1.2.7.7) active on 4-methyl-2-oxopentanoate, (S)-3-methyl-2-oxopentanoate, or 3-methyl-2-oxobutanoate
- Ignore hits to items matching 1.2.7.7 when looking for 'other' hits
- Ignore hits to items matching 1.2.7.11 when looking for 'other' hits
- Total: 2 characterized proteins
liuA: isovaleryl-CoA dehydrogenase
liuB: 3-methylcrotonyl-CoA carboxylase, alpha (biotin-containing) subunit
- Curated sequence CH_122249: 3-methylcrotonyl-CoA carboxylase biotin-containig subunit; EC 6.4.1.4
- Curated sequence Q42523: methylcrotonoyl-CoA carboxylase (EC 6.4.1.4). Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial; MCCase subunit alpha; 3-methylcrotonyl-CoA carboxylase 1; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.4
- Curated sequence Q9I299: methylcrotonoyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.4). methylcrotonyl-CoA carboxylase α-subunit (EC 6.4.1.4)
- Curated sequence Q2QMG2: Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial; MCCase subunit alpha; 3-methylcrotonyl-CoA carboxylase 1; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.4
- Curated sequence Q96RQ3: Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial; MCCase subunit alpha; 3-methylcrotonyl-CoA carboxylase 1; 3-methylcrotonyl-CoA carboxylase biotin-containing subunit; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.4. 3-methylcrotonyl-CoA carboxylase α subunit (EC 6.4.1.4)
- Curated sequence Q99MR8: Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial; MCCase subunit alpha; 3-methylcrotonyl-CoA carboxylase 1; 3-methylcrotonyl-CoA carboxylase biotin-containing subunit; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.4
- Curated sequence 6937189: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence SM_b21124: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence Pf1N1B4_3984: Methylcrotonyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.4)
- Curated sequence AO356_01595: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence Pf6N2E2_2194: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Ignore hits to items matching 6.4.1.4 when looking for 'other' hits
- Comment: 3-methylcrotonyl-CoA carboxylase has 2 subunits
- Total: 11 characterized proteins
liuD: 3-methylcrotonyl-CoA carboxylase, beta subunit
- Curated sequence Q9I297: methylcrotonoyl-CoA carboxylase (EC 6.4.1.4). methylcrotonyl-CoA carboxylase β-subunit (EC 6.4.1.4)
- Curated sequence Q9LDD8: methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence CH_122289: non-biotin containing subunit of 3-methylcrotonyl-CoA carboxylase; EC 6.4.1.4
- Curated sequence Q9HCC0: Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial; MCCase subunit beta; 3-methylcrotonyl-CoA carboxylase 2; 3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.4. 3-methylcrotonyl-CoA carboxylase β subunit (EC 6.4.1.4)
- Curated sequence Q9V9A7: Probable methylcrotonoyl-CoA carboxylase beta chain, mitochondrial; MCCase subunit beta; 3-methylcrotonyl-CoA carboxylase 2; 3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit; 3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.4
- Curated sequence 6937191: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence SM_b21122: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence GFF1050: Methylcrotonyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.4)
- Curated sequence AO356_01585: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Curated sequence Pf6N2E2_2192: Methylcrotonoyl-CoA carboxylase (EC 6.4.1.4)
- Ignore hits to items matching 6.4.1.4 when looking for 'other' hits
- Total: 10 characterized proteins
liuC: 3-methylglutaconyl-CoA hydratase
- Curated proteins or TIGRFams with EC 4.2.1.18
- UniProt sequence Q92VJ6: SubName: Full=Putative enoyl-CoA hydratase protein {ECO:0000313|EMBL:CAC49105.1}; EC=4.2.1.17 {ECO:0000313|EMBL:CAC49105.1};
- Comment: SM_b21126 (Q92VJ6) is a bit diverged and is confirmed by fitness data
- Total: 10 characterized proteins
liuE: hydroxymethylglutaryl-CoA lyase
atoA: acetoacetyl-CoA transferase, A subunit
- Curated sequence ATOD-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &alpha. ; acetyl-CoA:acetoacetyl-CoA transferase subunit α
- Curated sequence HP0691-MONOMER: Succinyl-CoA:3-ketoacid coenzyme A transferase subunit A; Succinyl-CoA:3-oxoacid CoA-transferase; OXCT A; EC 2.8.3.5. succinyl-CoA:acetoacetate CoA-transferase subunit A (EC 2.8.3.5)
- Curated sequence GFF1045: acetyl-CoA:acetoacetate CoA transferase, A subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2111: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit A
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
atoD: acetoacetyl-CoA transferase, B subunit
- Curated sequence ATOA-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &beta. ; acetyl-CoA:acetoacetyl-CoA transferase subunit β
- Curated sequence HP0692-MONOMER: succinyl-CoA:acetoacetate CoA-transferase subunit B (EC 2.8.3.5)
- Curated sequence GFF1044: acetyl-CoA:acetoacetate CoA transferase, B subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2112: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit B
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
aacS: acetoacetyl-CoA synthetase
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
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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