Definition of L-valine catabolism

As rules and steps, or see full text

Rules

Overview: Valine degradation in GapMind is based on MetaCyc pathway L-valine degradation I (link). The other pathways do not produce any fixed carbon and are not included.

• all: valine-transport, BKD, acdH, ech, bch, mmsB, mmsA and propionyl-CoA-degradation
  • Comment: An aminotransferase (not represented) forms 3-methyl-2-oxobutanoate, the decarboxylating alpha-ketoacid dehydrogenase (BKD) forms isobutanoyl-CoA, dehydrogenase acdH forms methylacrylyl-CoA (2-methylprop-2-enoyl-CoA), the hydratase ech forms (S)-3-hydroxy-isobutaonoyl-CoA, a hydrolase forms (S)-3-hydroxy-isobutanoate, a dehydrogenase forms (S)-methylmalonate semialdehyde (2-methyl-3-oxopropanoate), and a decarboxylating dehydrogenase forms propionyl-CoA.
• 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).
• propionyl-CoA-degradation:
  • prpC, prpD, acn and prpB
  • or prpC, acnD, prpF, acn and prpB
  • or propionyl-CoA-carboxylase, epi and methylmalonyl-CoA-mutase
  • or pco, hpcD, dddA and iolA
  • Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: propionyl-CoA is oxidized to acrylyl-CoA by pco, hydrated to 3-hydroxypropionyl-CoA, hydrolzed to 3-hydroxypropionate, oxidized to 3-oxopropionate (malonate semialdehyde), and oxidized to acetyl-CoA and CO2.
• methylmalonyl-CoA-mutase:
  • mcmA
  • or mcm-large and mcm-small
  • Comment: methylmalonyl-CoA mutase has a catalytic domain and a B12-binding domain. These are usually found in the same protein, which we call mcmA. In Metallosphaera and Pyrococcus, the B12-binding domain is a separate subunit. In Propionibacterium and Methylorubrum, there is an additional subunit with a catalytic domain only; this may have a protective role (PMID:14734568) and is not described here. There's also a mcm-interacting GTPase (known as MeaB or YgfD) that loads B12 onto mcm and protects it from inactivation (see PMC4631608); this is not described here. Some fused mcm proteins include a MeaB domain as well (i.e., Q8F222, Q8Y2U5).
• propionyl-CoA-carboxylase:
  • pccA and pccB
  • or pccA1, pccA2 and pccB
  • Comment: propionyl-CoA carboxylase is a heteromer, usually with alpha and beta subunits pccAB. Haloferax mediterranei has a third subunit as well (pccX), which is not described here. Acidianus brierleyi has a diverged pccA split into two pieces.
• valine-transport:
  • livF, livG, livJ, livH and livM
  • or natA, natB, natC, natD and natE
  • or Bap2
  • or brnQ
  • or phtJ
  • or bcaP
  • Comment: Transporters were identified using query: transporter:valine:L-valine:val

Steps

livF: L-valine 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};
• Comment: ABC transporters with 5 components: E. coli livFGHMJ and related systems (but the alternate substrate-binding protein livK does not transport valine). Related systems include livJFGHM from Streptococcus pneumoniae, braCDEFG from Pseudomonas aeruginosa (braC is the SBP), and braCDEFG or braC3/braDEFG from R. leguminosarum. In R. leguminosarum, the proximal braC (Q9L3M3) transports leucine (PMC135202), and likely valine as well. braC3 (RL3540; Q1MDE9) is a secondary SBP that transports leucine/isoleucine/valine/alanine (PMID:19597156). LivH/BraD = RL3750/Q1MCU0; LivM/BraE = RL3749/Q1MCU1; LivG/BraF = RL3748/Q1MCU2; LivF/BraG = RL3747/Q1MCU3. (The related liv system from Acidovorax, Ac3H11_1692:1695 and Ac3H11_2396, has not been shown to transport valine.)
• Total: 4 characterized proteins

livG: L-valine 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};
• Total: 4 characterized proteins

livJ: L-valine 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 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
• Total: 5 characterized proteins

livH: L-valine 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};
• Total: 4 characterized proteins

livM: L-valine 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};
• Comment: LivM from Streptococcus pneumoniae lacks an N-terminal domain of unknown function (DUF3382) that is found in E.coli and P. aeruginosa
• Total: 4 characterized proteins

natA: L-valine ABC transporter, ATPase component 1 (NatA)

• Ignore hits to Q55164 when looking for 'other' hits (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 sp. NatABCDE TC 3.A.1.4.2) and a similar system from Anabaena (also known as N-I; TC 3.A.1.4.6) are reported to transport many amino acids. There isn't any data for valine transport in Synechocystis, but N-I from Anabaena is thought to contribute to the reuptake of valine that leaks from the cell (PMC4500139).
• Total: 1 characterized proteins

natB: L-valine ABC transporter, substrate-binding component NatB

• Ignore hits to Q55387 when looking for 'other' hits (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: 1 characterized proteins

natC: L-valine ABC transporter, permease component 1 (NatC)

• Ignore hits to P74455 when looking for 'other' hits (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: 1 characterized proteins

natD: L-valine ABC transporter, permease component 2 (NatD)

• Ignore hits to P74318 when looking for 'other' hits (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: 1 characterized proteins

natE: L-valine ABC transporter, ATPase component 2 (NatE)

• Ignore hits to P73650 when looking for 'other' hits (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: 1 characterized proteins

Bap2: L-valine permease Bap2

• Curated sequence CH_091448: Leu/Val/Ile amino-acid permease. Leu/Val/Ile amino acid permease
• Curated sequence CH_091631: valine/tyrosine/tryptophan amino-acid permease. Valine/tyrosine/tryptophan amino-acid permease 1; Tyrosine and tryptophan amino acid transporter 1. Val/Tyr/Trp permease
• Curated sequence P38084: Leu/Val/Ile amino-acid permease; Branched-chain amino-acid permease 2
• Curated sequence P41815: Valine amino-acid permease; Branched-chain amino-acid permease 3. Valine amino-acid permease (Branched-chain amino-acid permease 3)
• Curated sequence Q2VQZ4: Arbuscular mycorrhizal fungal proline:H+ symporter, AAP1 (binds and probably transports nonpolar, hydrophobic amino acids)
• Total: 5 characterized proteins

brnQ: L-valine:cation symporter BrnQ/BraZ/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 P25185: Ile/Val:H+ symporter
• Curated sequence P19072: Branched chain amino acid: Na+ symporter
• Comment: E. coli BrnQ is reported to use Na+, while P. aeruginosa BraZ is reported to use H+
• Total: 3 characterized proteins

phtJ: L-valine uptake permease PhtJ

• Curated sequence Q5ZUB4: The valine uptake permease, PhtJ (required for maximal growth in macrophages and Acanthamoeba castellanii)
• Total: 1 characterized proteins

bcaP: L-valine uptake transporter BcaP/CitA

• 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

pccA: propionyl-CoA carboxylase, alpha subunit

• Curated sequence P05165: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3. propionyl-CoA carboxylase α chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q19842: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence I3R7G3: Propionyl-CoA carboxylase, biotin carboxylase and biotin-carboxyl carrier subunit; PCC; EC 6.4.1.3; EC 6.3.4.14. propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Curated sequence P0DTA4: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence Q5LUF3: Propionyl-CoA carboxylase alpha chain; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence Q91ZA3: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence MONOMER-13589: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8606: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence 3607308: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Curated sequence Dsui_0516: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 10 characterized proteins

pccB: propionyl-CoA carboxylase, beta subunit

• Curated sequence P05166: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase β chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q20676: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3)
• Curated sequence Q9X4K7: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence I3R7F1: Propionyl-CoA carboxylase, carboxyltransferase subunit; PCC; EC 6.4.1.3. propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence P53003: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3
• Curated sequence P79384: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3
• Curated sequence Q168G2: Propionyl-CoA carboxylase beta chain; EC 6.4.1.3
• Curated sequence Q3J4E3: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3. propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence Q99MN9: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-13598: acyl CoA carboxylase carboxyltransferase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence MONOMER-16260: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-17283: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-17284: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8607: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence 3607303: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Curated sequence Dsui_0517: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 16 characterized proteins

pccA1: propionyl-CoA carboxylase, biotin carboxyl carrier subunit

• Curated sequence MONOMER-13597: acyl CoA carboxylase biotin carboxylase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). biotin carboxylase (EC 6.3.4.14); acetyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

pccA2: propionyl-CoA carboxylase, biotin carboxylase subunit

• Curated sequence MONOMER-13596: acyl CoA carboxylase biotin carboxyl carrier protein subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

mcmA: methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components

• Curated sequence O86028: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2
• Curated sequence P22033: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase, mitochondrial; MCM; Methylmalonyl-CoA isomerase; EC 5.4.99.2. Methylmalonyl-CoA mutase, mitochondrial (EC 5.4.99.2)
• Curated sequence Q23381: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q84FZ1: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8MI68: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence P27253: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2). methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q3J4D7: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence MONOMER-18293: methylmalonyl-CoA mutase subunit (EC 5.4.99.2)
• Curated sequence Dsui_0519: Methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8F222: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8Y2U5: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 11 characterized proteins

mcm-large: methylmalonyl-CoA mutase, large (catalytic) subunit

• Curated sequence A4YEG1: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence O74009: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence P11653: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase large subunit; MCM-alpha; EC 5.4.99.2. methylmalonyl-CoA mutase large subunit (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 3 characterized proteins

mcm-small: methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit

• Curated sequence A4YIE3: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Curated sequence O58013: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 2 characterized proteins

prpC: 2-methylcitrate synthase

• Curated proteins or TIGRFams with EC 2.3.3.5
• Curated sequence P45858: citrate synthase (unknown stereospecificity) (EC 2.3.3.16). Citrate/2-methylcitrate synthase; 2-methylcitrate synthase; 2-MCS; MCS; Citrate synthase; EC 2.3.3.-; EC 2.3.3.16
• Comment: P45858 is annotated by SwissProt as 2-methylcitrate synthase, but without this EC number
• Total: 19 characterized proteins

prpD: 2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.79
• Total: 1 HMMs and 11 characterized proteins

acn: (2R,3S)-2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.99
• Ignore hits to items matching 4.2.1.3 when looking for 'other' hits
• Comment: (2R,3S)-2-methylcitrate dehydratases are closely related to aconitate hydratases (EC 4.2.1.3), which are ignored.
• Total: 1 HMMs and 10 characterized proteins

prpB: 2-methylisocitrate lyase

• Curated proteins or TIGRFams with EC 4.1.3.30
• Ignore hits to items matching 4.1.3.1 when looking for 'other' hits
• Comment: Many 2-methylisocitrate lyases are closely related to isocitrate lyases (EC 4.1.3.1)
• Total: 1 HMMs and 26 characterized proteins

acnD: 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)

• Curated proteins or TIGRFams with EC 4.2.1.117
• Ignore hits to Q937N8 when looking for 'other' hits (Aconitate hydratase A; Aconitase; (2R,3S)-2-methylisocitrate dehydratase; (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate dehydratase; Iron-responsive protein-like; IRP-like; Probable 2-methyl-cis-aconitate hydratase; RNA-binding protein; EC 4.2.1.3; EC 4.2.1.99)
• Comment: acnM from Ralstonia eutropha (Q937N8) is proposed to have this activity as well (PMID:11495997), but is annotated in SwissProt as aconitase or (2R,3S)-2-methylisocitrate dehydratase instead
• Total: 1 characterized proteins

prpF: methylaconitate isomerase

• Curated proteins or TIGRFams with EC 5.3.3.7
• Curated sequence Q937N7: 2-methyl-aconitate isomerase; Cis-trans isomerase; EC 5.3.3.-
• Ignore hits to A0A0A1H8I4 when looking for 'other' hits (Aconitate isomerase; AI; EC 5.3.3.7. aconitate DELTA-isomerase (EC 5.3.3.7))
• Comment: SwissProt annotates Q937N7 with this activity, but with a vague EC number. The periplasmic substrate-binding protein A0A0A1H8I4 has aconitate isomerase activity but has a high Km (PMID:26293748), and its periplasmic location would prevent it from participating in the methylcitrate cycle, so it is ignored.
• Total: 3 characterized proteins

epi: methylmalonyl-CoA epimerase

• Curated proteins or TIGRFams with EC 5.1.99.1
• Ignore hits to 3607309 when looking for 'other' hits (Methylmalonyl-CoA epimerase (EC 5.1.99.1))
• Comment: In the fitness browser reannotations, Dshi_0724 from Dinoroseobacter shibae (Dino:3607309) was annotated as the epimerase because it was annotated as such by SEED and it has a specific phenotype on propionate, which seemed to confirm its annotation. But Dshi_0724 belongs to the uncharacterized family DUF4174 / PF13778 and has a signal peptide. Also, D. shibae contains another, apparently essential, epi (Dshi_2630).
• Total: 1 HMMs and 9 characterized proteins

pco: propanyl-CoA oxidase

• Curated proteins or TIGRFams with EC 1.3.3.6
• Total: 27 characterized proteins

hpcD: 3-hydroxypropionyl-CoA dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.116
• Total: 3 characterized proteins

dddA: 3-hydroxypropionate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.59
• Total: 2 characterized proteins

iolA: malonate semialdehyde dehydrogenase (CoA-acylating)

• Curated proteins or TIGRFams with EC 1.2.1.18
• Ignore hits to items matching 1.2.1.27 when looking for 'other' hits
• Ignore hits to Q9I702 when looking for 'other' hits (Putative 3-oxopropanoate dehydrogenase; EC 1.2.1.-)
• Comment: Ignore similarity to methylmalonate semialdehyde dehydrogenase (EC 1.2.1.27), which often has this activity as well
• Total: 11 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

• Curated proteins or TIGRFams with EC 2.3.1.168
• Total: 11 characterized proteins

lpd: branched-chain alpha-ketoacid dehydrogenase, E3 component

• Curated proteins or TIGRFams with EC 1.8.1.4
• Total: 1 HMMs and 45 characterized proteins

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

acdH: isobutyryl-CoA dehydrogenase

• Curated proteins or TIGRFams with EC 1.3.8.5
• Ignore hits to 200844 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to GFF2715 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to Ac3H11_2996 when looking for 'other' hits (2-methyl-branched-chain-enoyl-CoA reductase (EC 1.3.8.5))
• Ignore hits to GFF2397 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to Pf1N1B4_4787 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to AO356_26355 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to Pf6N2E2_1146 when looking for 'other' hits (2-methylbutanoyl-CoA dehydrogenase (EC 1.3.8.5))
• Ignore hits to PfGW456L13_2983 when looking for 'other' hits (Short-chain acyl-CoA dehydrogenase (EC 1.3.8.1))
• Curated sequence GFF2392: isobutyryl-CoA dehydrogenase (EC 1.3.8.1)
• Ignore hits to MONOMER-17424 when looking for 'other' hits (short-chain acyl-CoA dehydrogenase monomer (EC 1.3.8.1))
• Comment: EC 1.3.8.5 includes isobutyryl-CoA dehydrogenases and sometimes (2S)-2-methylbutanoyl-CoA dehydrogenases (involved in isoleucine degradation, usually given EC 1.3.8.5 as well) or 3-methylbutanoyl-CoA dehydrogenases (involved in leucine degradation, usually given EC 1.3.8.4). Some enzymes act on all three methylacyl-CoA substrates. Other genes are required only for isoleucine degradation and their activity on isobutyryl-CoA is uncertain, so they are marked ignore. Also add Psest_2440 (GFF2392), given a different EC number, and ignore PfGW456L13_2983 (given a different EC but involved in isoleucine degradation) and PP_2216 (MONOMER-17424), also involved in isoleucine degradation.
• Total: 8 characterized proteins

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

bch: 3-hydroxyisobutyryl-CoA hydrolase

• Curated proteins or TIGRFams with EC 3.1.2.4
• Ignore hits to Q9SE41 when looking for 'other' hits (enoyl-CoA hydratase (EC 4.2.1.17))
• Ignore hits to MONOMER-11695 when looking for 'other' hits (enoyl-CoA hydratase subunit (EC 4.2.1.17))
• Total: 13 characterized proteins

mmsB: 3-hydroxyisobutyrate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.31
• Ignore hits to D5MU22 when looking for 'other' hits (aldehyde oxidase (EC 1.2.3.1))
• Comment: D5MU22 is probably mmsB but is misannotated in BRENDA
• Total: 1 HMMs and 6 characterized proteins

mmsA: methylmalonate-semialdehyde dehydrogenase

• Curated proteins or TIGRFams with EC 1.2.1.27
• Total: 1 HMMs and 15 characterized proteins