Definition of L-histidine catabolism

GapMind for catabolism of small carbon sources

Definition of L-histidine catabolism

As rules and steps, or see full text

Rules

Overview: Histidine utilization in GapMind is based on MetaCyc pathways L-histidine degradation I (link) or II (link). These pathways are very similar. Other pathways in MetaCyc (III-VI) are not complete or are not reported in prokaryotes, so they are not included.

all:

histidine-transport, hutH, hutU, hutI and hutG
or histidine-transport, hutH, hutU, hutI, hutH, hutF and hutG'
Comment: In pathway I, hutH deaminates histidine to urocanate, hutU hydrates it to 4-imidazolone-5-propanoate, hutI hydrolyzes it to N-formiminoglutamate, and hutG hydrolyzes it to formamide and glutamate. Formamide can be cleaved to formate and ammonia, but it could also be secreted, so this is not described. Similarly, formate may be oxidized to CO2 or secreted. Pathway II also involves conversion to N-formiminoglutamate, but then it is deaminated to N-formylglutamate by hutF, and hydrolyzed to formate and glutamate by hutG'.

histidine-transport:

hisP, hisM, hisQ and hisJ
or PA5503, PA5504 and PA5505
or Ac3H11_2562, Ac3H11_2561, Ac3H11_2560, Ac3H11_2555 and Ac3H11_2554
or natA, natB, natC, natD and natE
or aapJ, aapQ, aapM and aapP
or braC, braD, braE, braF and braG
or hutV, hutW and hutX
or bgtA and bgtB
or BPHYT_RS24000, BPHYT_RS24005, BPHYT_RS24010 and BPHYT_RS24015
or permease
or Ga0059261_1577
or S15A3
or LAT2
or LHT
or SLC38A3
or PTR2
Comment: Transporters were identified using query: transporter:histidine:L-histidine:his

Steps

hisP: L-histidine ABC transporter, ATPase component HisP

Curated sequence CH_003210: histidine transport ATP-binding protein hisP. Histidine transport ATP-binding protein HisP, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, ATP binding subunit (EC 7.4.2.1)
Curated sequence P02915: Histidine transport ATP-binding protein HisP. histidine transport atp-binding protein hisp. HisP aka STM2351, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
Curated sequence Q9HU32: Probable ATP-binding component of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
Ignore hits to AO356_09895 when looking for 'other' hits (ABC transporter for L-Lysine, ATPase component)
Comment: hisPMQJ from E.coli/Salmonella and PA5125-PA5155 from Pseudomona aeruginosa. A similar system in Pseudomonas fluorescens FW300-N2C3 is annotated as a lysine transporter but may well transport histidine, so it is ignored.
Total: 3 characterized proteins

hisM: L-histidine ABC transporter, permease component 1 (HisM)

Curated sequence P0A2I7: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM aka STM2352, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
Curated sequence P0AEU3: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisM (EC 7.4.2.1)
Curated sequence Q9HU29: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter membrane protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
Ignore hits to AO356_09910 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 2)
Total: 3 characterized proteins

hisQ: L-histidine ABC transporter, permease component 2 (HisQ)

Curated sequence P0A2I9: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ aka STM2353, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
Curated sequence P52094: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisQ (EC 7.4.2.1)
Curated sequence Q9HU30: Probable permease of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
Ignore hits to AO356_09905 when looking for 'other' hits (ABC transporter for L-Lysine, permease component 1)
Total: 3 characterized proteins

hisJ: L-histidine ABC transporter, substrate-binding component HisJ

Curated sequence CH_014295: histidine ABC transporter, periplasmic histidine-binding protein HisJ. Histidine-binding periplasmic protein, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. histidine ABC transporter periplasmic binding protein (EC 7.4.2.1)
Curated sequence CH_018185: histidine ABC transporter, periplasmic histidine-binding protein HisJ. Histidine-binding periplasmic protein; HBP
Curated sequence Q9HU31: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter periplasmic binding protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
Ignore hits to AO356_09900 when looking for 'other' hits (ABC transporter for L-Lysine, periplasmic substrate-binding component)
Total: 3 characterized proteins

PA5503: L-histidine ABC transporter, ATPase component

Curated sequence Q9HT70: Methionine import ATP-binding protein MetN 2, component of L-Histidine uptake porter, MetIQN
Comment: PA5503-PA5505 in P. aeruginosa (MetIQN in TCDB)
Total: 1 characterized proteins

PA5504: L-histidine ABC transporter, permease component

Curated sequence Q9HT69: D-methionine ABC transporter membrane protein, component of L-Histidine uptake porter, MetIQN
Total: 1 characterized proteins

PA5505: L-histidine ABC transporter, substrate-binding component

Curated sequence Q9HT68: Probable TonB-dependent receptor, component of L-Histidine uptake porter, MetIQN
Total: 1 characterized proteins

Ac3H11_2562: L-histidine ABC transporter, substrate-binding component 1

Curated sequence Ac3H11_2562: ABC transporter for L-Histidine, periplasmic substrate-binding component 2
Comment: 5-component 2-SBP system in Acidovorax sp. GW101-3H11
Total: 1 characterized proteins

Ac3H11_2561: L-histidine ABC transporter, permease component 1

Curated sequence Ac3H11_2561: ABC transporter for L-Histidine, permease component 2
Total: 1 characterized proteins

Ac3H11_2560: L-histidine ABC transporter, ATPase component

Curated sequence Ac3H11_2560: ABC transporter for L-Histidine, ATPase component
Total: 1 characterized proteins

Ac3H11_2555: L-histidine ABC transporter, substrate-binding component 2

Curated sequence Ac3H11_2555: ABC transporter for L-Histidine, periplasmic substrate-binding component 1
Total: 1 characterized proteins

Ac3H11_2554: ABC transporter for L-Histidine, permease component 2

Curated sequence Ac3H11_2554: ABC transporter for L-Histidine, permease component 1
Total: 1 characterized proteins

natA: L-histidine 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
Ignore hits to Q7A2H0 when looking for 'other' hits (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; a similar system in Anabaena is not included as it appears to use some other SBP for histidine (but the non-SPB components are marked ignore)
Total: 1 characterized proteins

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

Curated sequence Q55387: NatB aka SLR0559, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
Total: 1 characterized proteins

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

Curated sequence P74455: NatC aka SLL0146, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
Ignore hits to Q8YY08 when looking for 'other' hits (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-histidine 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
Ignore hits to Q8YXD0 when looking for 'other' hits (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-histidine 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
Ignore hits to Q8YT15 when looking for 'other' hits (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

aapJ: L-histidine ABC transporter, substrate-binding component AapJ

Curated sequence SMc02118: ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, periplasmic substrate-binding component
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)
Comment: aapJQMP from Rhizobium leguminosarum and Sinorhizobium meliloti
Total: 2 characterized proteins

aapQ: L-histidine ABC transporter, permease component 1 (AapQ)

Curated sequence SMc02119: ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, permease component 1
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)
Total: 2 characterized proteins

aapM: L-histidine ABC transporter, permease component 2 (AapM)

Curated sequence SMc02120: ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, permease component 2
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)
Total: 2 characterized proteins

aapP: L-histidine ABC transporter, ATPase component AapP

Curated sequence SMc02121: ABC transporter for L-Glutamine, L-Histidine, and other L-amino acids, ATPase component
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)
Total: 2 characterized proteins

braC: ABC transporter for glutamate, histidine, arginine, and other amino acids, substrate-binding component BraC

Curated sequence Q9L3M3: BraC, component of General L- (and D-)amino acid uptake porter (transports acidic, basic, polar, semipolar and hydrophobic amino acids). The amino and carboxyl groups do not need to be α since γ-aminobutyric acid (GABA) is a substrate. The system may function with additional binding proteins since L-alanine uptake is not dependent on BraC
Comment: In Rhizobium leguminosarum, a broad-specificity amino acid ABC transporter is known as braCDEFG. (A homologous system from Pseudomonas is thought to have a narrower substrate range.)
Total: 1 characterized proteins

braD: ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 1 (BraD)

UniProt sequence Q1MCU0: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09240.1};
Total: 1 characterized proteins

braE: ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 2 (BraE)

UniProt sequence Q1MCU1: SubName: Full=Transmembrane component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09239.1};
Total: 1 characterized proteins

braF: ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 1 (BraF)

UniProt sequence Q1MCU2: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09238.1};
Total: 1 characterized proteins

braG: ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 2 (BraG)

UniProt sequence Q1MCU3: SubName: Full=ATP-binding component of a broad range amino acid ABC transporter {ECO:0000313|EMBL:CAK09237.1};
Total: 1 characterized proteins

hutV: L-histidine 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
Curated sequence AO356_09610: ABC transporter for L-Histidine, ATPase component
Comment: hutVWX from Sinorhizobium meliloti and Pseudomonas fluorescens FW300-N2C3
Total: 2 characterized proteins

hutW: L-histidine ABC transporter, permease component HutW

Curated sequence AO356_09615: ABC transporter for L-Histidine, permease component
Curated sequence Q9KKE2: HutW aka HISW, component of Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
Total: 2 characterized proteins

hutX: L-histidine ABC transporter, substrate-binding component HutX

Curated sequence Q9KKE3: HutX aka HISX, component of Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
Curated sequence AO356_09620: ABC transporter for L-Histidine, periplasmic substrate-binding component
Total: 2 characterized proteins

bgtA: L-histidine ABC transporter, ATPase component BgtA

Curated sequence P73721: BgtA aka SLR1735, component of Arginine/lysine/histidine/glutamine porter
Comment: bgtAB from Synechocystis
Total: 1 characterized proteins

bgtB: L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)

Curated sequence P73544: BgtB aka GLNH aka SLL1270, component of Arginine/lysine/histidine/glutamine porter
Curated sequence Q8YSA2: Basic amino acid uptake transporter, BgtAB
Total: 2 characterized proteins

BPHYT_RS24000: L-histidine ABC transporter, substrate-binding component

UniProt sequence B2TBJ6: SubName: Full=Extracellular solute-binding protein family 3 {ECO:0000313|EMBL:ACD19199.1}; Flags: Precursor;
Comment: BPHYT_RS24000:BPHYT_RS24015 from Burkholderia phytofirmans PsJN is specifically important for histidine utilization. (There's no fitness data for _RS24015.)
Total: 1 characterized proteins

BPHYT_RS24005: L-histidine ABC transporter, permease component 1

UniProt sequence B2TBJ7: SubName: Full=Polar amino acid ABC transporter, inner membrane subunit {ECO:0000313|EMBL:ACD19200.1}; Flags: Precursor;
Total: 1 characterized proteins

BPHYT_RS24010: L-histidine ABC transporter, permease component 2

UniProt sequence B2TBJ8: SubName: Full=Polar amino acid ABC transporter, inner membrane subunit {ECO:0000313|EMBL:ACD19201.1};
Total: 1 characterized proteins

BPHYT_RS24015: L-histidine ABC transporter, ATPase component

UniProt sequence B2TBJ9: SubName: Full=ABC transporter related {ECO:0000313|EMBL:ACD19202.1};
Total: 1 characterized proteins

permease: L-histidine permease

Curated sequence A2RI97: Histidine permease HisP
Curated sequence CH_091109: histidine permease. Histidine permease. High affinity histidine permease (also implicated in Mn2+ efflux; Co2+, Ni2+, Zn2+ and Cu2+ uptake)
Curated sequence CH_091412: uncharacterized amino-acid permease C869.11. The basic amino acid (canavanine sensitivity) transporter, Cat1
Curated sequence P43059: The high affinity basic amino acid (Arg, Lys, His) transporter, Can1
Curated sequence Q46065: Aromatic amino acid permease, AroP
Curated sequence AO353_12275: histidine permease
Total: 6 characterized proteins

Ga0059261_1577: L-histidine transporter

Curated sequence Ga0059261_1577: L-glutamine and L-histidine transporter
Total: 1 characterized proteins

S15A3: L-histidine transporter

Curated sequence O09014: Solute carrier family 15 member 4; Peptide transporter 4; Peptide/histidine transporter 1; rPHT1
Curated sequence Q8BPX9: Solute carrier family 15 member 3; Peptide transporter 3; Peptide/histidine transporter 2; cAMP-inducible gene 1 protein
Curated sequence Q8IY34: Solute carrier family 15 member 3; Osteoclast transporter; Peptide transporter 3; Peptide/histidine transporter 2. solute carrier family 15, member 3, di- and tri-peptide uptake transporter in immune cells
Curated sequence Q8N697: Solute carrier family 15 member 4; Peptide transporter 4; Peptide/histidine transporter 1; hPHT1. Solute carrier family 15 member 4 (Peptide transporter 4) (Peptide/histidine transporter 1) (hPHT1) present in immune cells
Curated sequence Q924V4: Solute carrier family 15 member 3; Peptide transporter 3; Peptide/histidine transporter 2
Total: 5 characterized proteins

LAT2: L-histidine transporter

Curated sequence Q9WVR6: Large neutral amino acids transporter small subunit 2; L-type amino acid transporter 2; Solute carrier family 7 member 8. L-type neutral amino acid transporter, LAT2 (Na+-independent with broad specificity for all L-isomers of neutral amino acids; preferred substrate: Phe, His, Trp, Ile, Val, Leu, Gln, Cys, Ser; catalyzes obligatory exchange with μM affinities on the outside and mM affinities on the inside [1000x difference]). Both LAT2 and LAT1 (2.A.3.8.1) catalyze uptake of S-nitro-L-cysteine (Li and Whorton, 2005). Also transports thyroid hormones
Curated sequence O34739: Serine/threonine exchanger SteT. The Ser/Thr exchange transporter (SteT) (also transports aromatic amino acids with lower efficiency) (Reig et al., 2007). The substrate-bound state of SteT shows increased conformational flexibility and kinetic stability, enabling transport of substrate across the cell membrane (Bippes et al. 2009). TMS8 sculpts the substrate-binding site and undergoes conformational changes during the transport cycle of SteT (Bartoccioni et al., 2010). Mutations allow substrate binding but not translocation. Other mutations stabilize the protein and result in higher production levels
Curated sequence Q26594: The schistosome neutral and cationic amino acid transporter, SPRM1lc (Na+-independent), (takes up phe, arg, lys, ala, gln, his, trp and leu; functions with SPRM1hc (TC# 8.A.9.3.1)
Curated sequence Q9NA91: Aromatic amino acid exchanger, AAT-9 (Veljkovic et al., 2004b)
Total: 4 characterized proteins

LHT: L-histidine transporter

Curated sequence Q9FKS8: Lysine histidine transporter 1. Lysine/histidine transporter, LHT1
Curated sequence Q9LRB5: Lysine histidine transporter 2; AtLHT2; Amino acid transporter-like protein 2. Lysine/histidine transporter 2 (AtLHT2) (Amino acid transporter-like protein 2)
Curated sequence Q9SX98: Lysine histidine transporter-like 8; Amino acid transporter-like protein 1. Lysine histidine transporter-like 8 (Amino acid transporter-like protein 1)
Curated sequence Q84WE9: Lysine-Histidine Transporter-7 (LHT7) found in mature pollen (Bock et al., 2006) (most like 2.A.18.2.2; 30% identity)
Total: 4 characterized proteins

SLC38A3: L-histidine:Na+ symporter

Curated sequence CH_091437: sodium-coupled neutral amino acid transporter 3. Sodium-coupled neutral amino acid transporter 3; N-system amino acid transporter 1; Na(+)-coupled neutral amino acid transporter 3; Solute carrier family 38 member 3; System N amino acid transporter 1. System N1, SNAT3 [glutamine/histidine/asparagine/alanine]:[Na+ + H+] sym/antiporter (1 aa + 2 Na+ cotransported against 1 H+ antiported out) (probable orthologue of mNAT). Li+ can substitute for Na+; system N1 can function bidirectionally. SNAT3 is a primarily a glutamine transporter required for amino acid homeostasis. Loss cannot be compensated, suggesting that this transporter is a major route of glutamine transport in the liver, brain, and kidney
Curated sequence CH_091510: sodium-coupled neutral amino acid transporter 3. Sodium-coupled neutral amino acid transporter 3; N-system amino acid transporter 1; Na(+)-coupled neutral amino acid transporter 3; Solute carrier family 38 member 3; mNAT; System N amino acid transporter 1. Liver histidine and glutamine specific system N-like, Na+-dependent amino acid transporter, mNAT. Also called SNAT3. SNAT3 trafficking occurs in a dynamin-independent manner and is influenced by caveolin
Total: 2 characterized proteins

PTR2: L-histidine:H+ symporter

Curated sequence P46032: Protein NRT1/ PTR FAMILY 8.3; AtNPF8.3; Histidine-transporting protein; Peptide transporter PTR2. Histidine or peptide:H+ symporter
Curated sequence Q43390: Nitrate (chlorate) or histidine:H+ symporter
Total: 2 characterized proteins

hutH: histidine ammonia-lyase

Curated proteins or TIGRFams with EC 4.3.1.3
Total: 1 HMMs and 20 characterized proteins

hutU: urocanase

Curated proteins or TIGRFams with EC 4.2.1.49
Total: 1 HMMs and 16 characterized proteins

hutI: imidazole-5-propionate hydrolase

Curated proteins or TIGRFams with EC 3.5.2.7
Total: 1 HMMs and 14 characterized proteins

hutG: N-formiminoglutamate formiminohydrolase

Curated proteins or TIGRFams with EC 3.5.3.8
Total: 1 HMMs and 5 characterized proteins

hutF: N-formiminoglutamate deiminase

Curated proteins or TIGRFams with EC 3.5.3.13
Total: 1 HMMs and 11 characterized proteins

hutG': N-formylglutamate amidohydrolase

Curated proteins or TIGRFams with EC 3.5.1.68
Total: 1 HMMs and 12 characterized proteins

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Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
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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 2024 update on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer

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

GapMind for catabolism of small carbon sources