Definition of L-proline catabolism
As rules and steps, or see full text
Rules
Overview: Proline degradation in GapMind is based on MetaCyc pathway I via glutamate semialdehyde dehydrogenase (link) and pathway II via 5-aminopentanoate (link). (MetaCyc describes 5-aminopentanoate, also known as 5-aminovalerate, as a fermentative end product, but it is further degraded
- all: proline-transport and proline-degradation
- 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.
- 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.
- D-proline-reductase: prdA, prdB and prdC
- Comment: D-proline reductase includes components PrdA and PrdB and electron transfer protein PrdC
- proline-transport:
- proV, proW and proX
- or opuBA and opuBB
- or natA, natB, natC, natD and natE
- or hutV, hutW and hutX
- or AZOBR_RS08235, AZOBR_RS08240, AZOBR_RS08245, AZOBR_RS08250 and AZOBR_RS08260
- or HSERO_RS00870, HSERO_RS00885, HSERO_RS00890, HSERO_RS00895 and HSERO_RS00900
- or aapJ, aapQ, aapM and aapP
- or proY
- or putP
- or PROT1
- or SLC6A7
- or proP
- or ectP
- or betS
- or BAC2
- or AAT20.2
- or CCNA_00435
- or N515DRAFT_2924
- Comment: Transporters were identified using query: transporter:proline:L-proline
Steps
proV: proline ABC transporter, ATPase component ProV
- Curated sequence CH_001555: glycine betaine/l-proline transport atp-binding protein prov. Glycine betaine/proline betaine transport system ATP-binding protein ProV. ProV aka B2677, component of Glycine betaine/proline porter, ProU or ProVWX (also transports proline betaine, carnitine, dimethyl proline, homobetaine, γ-butyrobetaine and choline with low affinity). glycine betaine ABC transporter ATP binding subunit ProV (EC 7.6.2.9). glycine betaine ABC transporter ATP binding subunit ProV (EC 7.6.2.9)
- Curated sequence P17328: Glycine betaine/proline betaine transport system ATP-binding protein ProV
- Ignore hits to E0SCY1 when looking for 'other' hits (Glycine betaine/choline transport system ATP-binding protein OusV)
- Comment: E.coli/Salmonella have proVWX (only ProV is curated in S. typhimurium). Ignore a similar system in Dickeya dadantii (or Erwinia chrysanthemi) reported to act on glycine betaine only
- Total: 2 characterized proteins
proW: proline ABC transporter, permease component ProW
- Curated sequence P14176: Glycine betaine/proline betaine transport system permease protein ProW. ProW aka B2678, component of Glycine betaine/proline porter, ProU or ProVWX (also transports proline betaine, carnitine, dimethyl proline, homobetaine, γ-butyrobetaine and choline with low affinity). glycine betaine ABC transporter membrane subunit ProW (EC 7.6.2.9). glycine betaine ABC transporter membrane subunit ProW (EC 7.6.2.9)
- Ignore hits to E0SCY2 when looking for 'other' hits (Glycine betaine/choline transport system permease protein OusW)
- Total: 1 characterized proteins
proX: proline ABC transporter, substrate-binding component ProX
- Curated sequence CH_024698: glycine betaine-binding periplasmic protein. Glycine betaine/proline betaine-binding periplasmic protein; GBBP. ProX aka ProU aka B2679, component of Glycine betaine/proline porter, ProU or ProVWX (also transports proline betaine, carnitine, dimethyl proline, homobetaine, γ-butyrobetaine and choline with low affinity). glycine betaine ABC transporter periplasmic binding protein ProX (EC 7.6.2.9). glycine betaine ABC transporter periplasmic binding protein ProX (EC 7.6.2.9)
- Ignore hits to E0SCY3 when looking for 'other' hits (Glycine betaine-binding periplasmic protein OusX)
- Total: 1 characterized proteins
opuBA: proline ABC transporter, ATPase component OpuBA/BusAA
- Curated sequence Q93A35: BilEA aka OpuBA protein, component of A proline/glycine betaine uptake system. Also reported to be a bile exclusion system that exports oxgall and other bile compounds, BilEA/EB or OpuBA/BB (required for normal virulence)
- Curated sequence Q9RQ06: BusAA, component of Uptake system for glycine-betaine (high affinity) and proline (low affinity) (OpuAA-OpuABC) or BusAA-ABC of Lactococcus lactis). BusAA, the ATPase subunit, has a C-terminal tandem cystathionine β-synthase (CBS) domain which is the cytoplasmic K+ sensor for osmotic stress (osmotic strength)while the BusABC subunit has the membrane and receptor domains fused to each other (Biemans-Oldehinkel et al., 2006; Mahmood et al., 2006; Gul et al. 2012). An N-terminal amphipathic α-helix of OpuA is necessary for high activity but is not critical for biogenesis or the ionic regulation of transport
- Comment: In Listeria monocytogenes and in Lactococcus lactis, the permease is fused to the substrate-binding component.
- Total: 2 characterized proteins
opuBB: proline ABC transporter, fused permease and substrate-binding components OpuBB/BusAB
- Curated sequence Q93A34: BilEB aka OpuBB protein, component of A proline/glycine betaine uptake system. Also reported to be a bile exclusion system that exports oxgall and other bile compounds, BilEA/EB or OpuBA/BB (required for normal virulence)
- Curated sequence Q9RQ05: BusAB aka OPUABC, component of Uptake system for glycine-betaine (high affinity) and proline (low affinity) (OpuAA-OpuABC) or BusAA-ABC of Lactococcus lactis). BusAA, the ATPase subunit, has a C-terminal tandem cystathionine β-synthase (CBS) domain which is the cytoplasmic K+ sensor for osmotic stress (osmotic strength)while the BusABC subunit has the membrane and receptor domains fused to each other (Biemans-Oldehinkel et al., 2006; Mahmood et al., 2006; Gul et al. 2012). An N-terminal amphipathic α-helix of OpuA is necessary for high activity but is not critical for biogenesis or the ionic regulation of transport
- Ignore hits to Q7DAU8 when looking for 'other' hits (ABC-type quaternary amine transporter (EC 7.6.2.9))
- Comment: Ignore a nearly-identical protein from L. lactis, annotated as a quarternary amine transporter
- Total: 2 characterized proteins
natA: proline 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 sp. NatABCDE; also a similar system in Anabaena
- Total: 2 characterized proteins
natB: proline 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: proline 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: proline 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: proline 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
hutV: proline ABC transporter, ATPase component HutV
- Curated sequence Q9KKE1: HutV aka HISV aka R02702 aka SMC00670, component of Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
- Comment: Ensifer meliloti (formerly Rhizobium or Sinorhizobium) hutVWX
- Total: 1 characterized proteins
hutW: proline ABC transporter, permease component HutW
- Curated sequence Q9KKE2: HutW aka HISW, component of Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
- Total: 1 characterized proteins
hutX: proline ABC transporter, substrate-binding component HutX
- Curated sequence Q9KKE3: HutX aka HISX, component of Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
- Total: 1 characterized proteins
AZOBR_RS08235: proline ABC transporter, permease component 1
- Curated sequence AZOBR_RS08235: L-proline and D-alanine ABC transporter, permease component 1
- Comment: Azospirillum brasilense -- just one component is in the reannotations, but all show up in the fitness data for proline.
- Total: 1 characterized proteins
AZOBR_RS08240: proline ABC transporter, permease component 2
- UniProt sequence G8ALI9: SubName: Full=Leucine/isoleucine/valine ABC transporter,permease component {ECO:0000313|EMBL:CCC98101.1};
- Total: 1 characterized proteins
AZOBR_RS08245: proline ABC transporter, ATPase component 1
- UniProt sequence G8ALJ0: SubName: Full=Leucine/isoleucine/valine ABC transporter,ATPase component {ECO:0000313|EMBL:CCC98102.1}; EC=3.6.3.- {ECO:0000313|EMBL:CCC98102.1};
- Total: 1 characterized proteins
AZOBR_RS08250: proline ABC transporter, ATPase component 2
- UniProt sequence G8ALJ1: SubName: Full=Leucine//isoleucine/valine ABC transporter,ATPase component {ECO:0000313|EMBL:CCC98103.1}; EC=3.6.3.- {ECO:0000313|EMBL:CCC98103.1};
- Total: 1 characterized proteins
AZOBR_RS08260: proline ABC transporter, substrate-binding component
- UniProt sequence G8ALJ3: SubName: Full=Branched-chain amino acid ABC transporter,substrate-binding periplasmic component {ECO:0000313|EMBL:CCC98105.1};
- Total: 1 characterized proteins
HSERO_RS00870: proline ABC transporter, substrate-binding component
- UniProt sequence D8IUY1: SubName: Full=ABC-type branched-chain amino acid transport system, periplasmic component protein {ECO:0000313|EMBL:ADJ61700.1};
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Comment: 5-part ABC transporter in Herbaspirillum brasilense, identified using fitness data. (This system is distantly related to AZOBR_RS08235:RS08260.) A related system from Acidovorax sp. GW101-3H11 is also important for proline utilization: Ac3H11_2396 (A0A165KTD4), Ac3H11_1695 (A0A165KC95), Ac3H11_1694 (A0A165KER0), Ac3H11_1693 (A0A165KC86), Ac3H11_1692 (A0A165KC78).
- Total: 2 characterized proteins
HSERO_RS00885: proline ABC transporter, permease component 1
- UniProt sequence D8IUY4: SubName: Full=ABC-type branched-chain amino acid transport system, permease component protein {ECO:0000313|EMBL:ADJ61703.1};
- UniProt sequence A0A165KC95: SubName: Full=ABC transporter permease {ECO:0000313|EMBL:KZT15319.1};
- Total: 2 characterized proteins
HSERO_RS00890: proline ABC transporter, permease component 2
- UniProt sequence D8IUY5: SubName: Full=ABC-type branched-chain amino acid transport system, permease component protein {ECO:0000313|EMBL:ADJ61704.1};
- UniProt sequence A0A165KER0: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15410.1};
- Total: 2 characterized proteins
HSERO_RS00895: proline ABC transporter, ATPase component 1
- UniProt sequence D8J1T6: SubName: Full=ABC-type branched-chain amino acid transport system, ATPase component protein {ECO:0000313|EMBL:ADJ62707.1};
- UniProt sequence A0A165KC86: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15318.1};
- Total: 2 characterized proteins
HSERO_RS00900: proline ABC transporter, ATPase component 2
- UniProt sequence D8IUY7: SubName: Full=ABC-type branched-chain amino acid transport system, ATPase component protein {ECO:0000313|EMBL:ADJ61706.1};
- UniProt sequence A0A165KC78: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15317.1};
- 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
proY: proline:H+ symporter
- Curated sequence Q2VQZ4: Arbuscular mycorrhizal fungal proline:H+ symporter, AAP1 (binds and probably transports nonpolar, hydrophobic amino acids)
- Curated sequence CH_091285: proline-specific permease. Proline-specific permease. Proline permease
- Curated sequence CH_122066: proline-specific permease (proline transport protein)
- Curated sequence P46349: GABA permease; 4-amino butyrate transport carrier; Gamma-aminobutyrate permease; Proline transporter GabP. β-alanine/γ-aminobutyrate/proline/3,4-dehydroproline:H+ symporter, GabP
- Curated sequence Q9URZ3: Probable proline-specific permease put4
- Curated sequence P0AAE2: ProY of 457 aas and 12 TMSs
- Curated sequence P37460: Proline-specific permease (ProY)
- Total: 7 characterized proteins
putP: proline:Na+ symporter
- Curated sequence O06493: Osmoregulated proline transporter OpuE; Osmoprotectant uptake; Proline uptake system. Proline uptake porter, OpuE (YerK)
- Curated sequence P07117: Sodium/proline symporter; Proline permease; Propionate transporter. Proline:Na+ symporter, PutP. proline:Na+ symporter. proline:Na+ symporter
- Curated sequence P94392: High-affinity proline transporter PutP. The high affinity nutritional proline uptake porter, PutP
- Curated sequence Q2FWY7: Sodium/proline symporter; Proline permease. Sodium/proline symporter (Proline permease)
- Curated sequence O24896: High affinity proline-specific Na+:proline symporter, PutP (Rivera-Ordaz et al. 2013). Proline is a preferred source of energy for this microaerophilic bacterium. PutP is efficiently inhibited by the proline analogs, 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid
- Curated sequence Q9I5F5: L-proline uptake porter, PutP
- Total: 6 characterized proteins
PROT1: proline transporter
- Curated sequence CH_091590: proline transporter 1. Proline transporter 1; AtPROT1. Proline permease 1
- Curated sequence P92962: Proline transporter 2; AtPROT2
- Curated sequence Q60DN5: Proline transporter 1; OsPROT
- Curated sequence Q9SJP9: Proline transporter 3; AtPROT3
- Curated sequence Q9XE48: Proline/GABA/glycine betaine permease, ProT1
- Total: 5 characterized proteins
SLC6A7: proline:Na+ symporter
- Curated sequence CH_091144: sodium-dependent proline transporter. Proline:Na+ symporter
- Curated sequence Q64093: Sodium- and chloride-dependent transporter XTRP3; Sodium/imino-acid transporter 1; Solute carrier family 6 member 20; Transporter rB21A. sodium- and chloride-dependent transporter XTRP3. Na+/Amino acid transporter 1, SIT1/IMINO (SLC6A20). Transports imino acids such as proline (Km=0.2 mM), pipecolate, and N-methylated amino acids such as MeAIB and sarcosine (Na+-dependent, Cl--stimulated, pH-independent, voltage-dependent) (Li+, but not H+ can substitute for Na+) (Takanaga et al., 2005). It is a 2Na+/1Cl--proline cotransporter
- Curated sequence P48065: Betaine/GABA:Na+ symporter, BGT1. (Substrates include: betaine, GABA, diaminobutyrate, β-alanine, proline, quinidine, dimethylglycine, glycine, and sarcosine with decreasing affinity in that order)
- Curated sequence Q99884: Sodium-dependent proline transporter (Solute carrier family 6 member 7)
- Total: 4 characterized proteins
proP: proline:H+ symporter ProP
- Curated sequence CH_024324: proline porter II. Proline/betaine transporter; Proline porter II; PPII. (Proline/glycine-betaine):(H+/Na+) symporter, ProP (also transports taurine, ectoine, pipecolate, proline-betaine, N,N-dimethylglycine, carnitine, and 1-carboxymethyl-pyridinium) (subject to osmotic activation). Transmembrane helix I and periplasmic loop 1 are involved in osmosensing and osmoprotectant transport. osmolyte:H+ symporter ProP. osmolyte:H+ symporter ProP
- Curated sequence Q47421: Glycine betaine/proline/ectoine/pipecolic acid transporter OusA; Osmoprotectant uptake system A
- Curated sequence Q79VC4: Ectoine/proline transporter ProP
- Total: 3 characterized proteins
ectP: proline transporter EctP
- Curated sequence Q79VE0: Ectoine/glycine betaine/proline transporter EctP. Ectosine/glycine betaine/proline:Na+ symporter
- Curated sequence Q87NZ5: Glycine betaine/proline/choline transporter VP1723
- Curated sequence Q87PP5: Glycine betaine/proline/choline/ectoine transporter VP1456
- Total: 3 characterized proteins
betS: proline transporter BetS
- Curated sequence G3XCN6: Glycine betaine/proline betaine transporter BetS. Glycine-betaine/proline-betaine:Na+ symporter, BetS; BetT, OpuD
- Total: 1 characterized proteins
BAC2: basic amino acid carrier BAC2
- Curated sequence Q9CA93: Mitochondrial arginine transporter BAC2; Mitochondrial basic amino acid carrier 2; AtMBAC2. Basic amino acid carrier2, BAC2 of 296 aas and 6 TMSs
- Total: 1 characterized proteins
AAT20.2: proline transporter
- Curated sequence A4HUI4: Proline/alanine transporter of 488 aas and 10 TMSs, AAP24. The first 18 amino acids of the negatively charged N-terminal LdAAP24 tail are required for alanine transport and may facilitate the electrostatic interactions of the entire negatively charged N-terminal tail with the positively charged internal loops in the transmembrane domain
- Total: 1 characterized proteins
CCNA_00435: proline transporter
- UniProt sequence A0A0H3C3Q5: SubName: Full=Amino acid transporter {ECO:0000313|EMBL:ACL93902.2};
- Comment: Identified using fitness data for Caulobacter crescentus
- Total: 1 characterized proteins
N515DRAFT_2924: proline transporter
- UniProt sequence A0A1I1Y8J0: SubName: Full=Basic amino acid/polyamine antiporter, APA family {ECO:0000313|EMBL:SFE15955.1};
- Comment: Identified using fitness data for Dyella japonica
- Total: 1 characterized proteins
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
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
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
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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