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 the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code.
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