Definition of L-histidine biosynthesis
As rules and steps, or see full text
Rules
Overview: Histidine biosynthesis in GapMind is based on the MetaCyc pathway (link).
Steps
prs: ribose-phosphate diphosphokinase
hisG: ATP phosphoribosyltransferase
hisI: phosphoribosyl-ATP pyrophosphatase
- Curated proteins or TIGRFams with EC 3.6.1.31
- Ignore hits to CH_123581 when looking for 'other' hits (multifunctional enzyme that catalyzes three steps of histidine biosynthesis)
- Ignore hits to A1BPP9 when looking for 'other' hits (histidinol dehydrogenase (EC 1.1.1.23))
- Comment: CH_123581 and A1BPP9 probably do all three: hisD, hisE, and hisI.
- Total: 1 HMMs and 18 characterized proteins
hisE: phosphoribosyl-AMP cyclohydrolase
- Curated proteins or TIGRFams with EC 3.5.4.19
- HMM PF01502
- Ignore hits to CH_123581 when looking for 'other' hits (multifunctional enzyme that catalyzes three steps of histidine biosynthesis)
- Ignore hits to A1BPP9 when looking for 'other' hits (histidinol dehydrogenase (EC 1.1.1.23))
- Comment: A1BPP9 is annotated as hisD but is likely multifunctional, so similarity to it is ignored.
- Total: 1 HMMs and 8 characterized proteins
hisA: 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase
hisF: imidazole glycerol phosphate synthase, cyclase subunit
- Curated proteins matching hisF
- HMM TIGR00735
- Ignore hits to items matching imidazole glycerol phosphate synthase when looking for 'other' hits
- Curated sequence Q5NMD6: imidazole glycerol-phosphate synthase (subunit 2/2) (EC 4.3.2.10)
- Curated sequence Q8ZY16: imidazole glycerol-phosphate synthase (subunit 2/2) (EC 4.3.2.10)
- Curated sequence A4WHB6: imidazole glycerol-phosphate synthase (subunit 2/2) (EC 4.3.2.10)
- Curated sequence Q9SZ30: imidazole glycerol-phosphate synthase (EC 4.3.2.10). imidazole-glycerol-phosphate synthase (EC 4.3.2.10)
- Comment: Subunits are not always annotated consistently, so are added manually, and Q9SZ30 is a fusion protein of the two subunits
- Total: 1 HMMs and 7 characterized proteins
hisH: imidazole glycerol phosphate synthase, amidotransferase subunit
- Curated proteins matching hisH
- Curated proteins matching IGP synthase, amidotransferase subunit
- HMM TIGR01855
- Ignore hits to items matching imidazole glycerol phosphate synthase when looking for 'other' hits
- Curated sequence Q5NMD4: imidazole glycerol-phosphate synthase (subunit 1/2) (EC 4.3.2.10)
- Curated sequence Q8ZY40: imidazole glycerol-phosphate synthase (subunit 1/2) (EC 4.3.2.10)
- Curated sequence Q9SZ30: imidazole glycerol-phosphate synthase (EC 4.3.2.10). imidazole-glycerol-phosphate synthase (EC 4.3.2.10)
- Curated sequence A4WHA5: imidazole glycerol-phosphate synthase (subunit 1/2) (EC 4.3.2.10)
- Comment: Subunits are not always annotated consistently, so are added manually, and Q9SZ30 is a fusion protein of the two subunits
- Total: 1 HMMs and 11 characterized proteins
hisB: imidazoleglycerol-phosphate dehydratase
- Curated proteins or TIGRFams with EC 4.2.1.19
- UniProt sequence B2SZ63: RecName: Full=Imidazoleglycerol-phosphate dehydratase {ECO:0000255|HAMAP-Rule:MF_00076}; Short=IGPD {ECO:0000255|HAMAP-Rule:MF_00076}; EC=4.2.1.19 {ECO:0000255|HAMAP-Rule:MF_00076};
- UniProt sequence Q9HU41: RecName: Full=Imidazoleglycerol-phosphate dehydratase {ECO:0000255|HAMAP-Rule:MF_00076}; Short=IGPD {ECO:0000255|HAMAP-Rule:MF_00076}; EC=4.2.1.19 {ECO:0000255|HAMAP-Rule:MF_00076};
- Comment: Fitness data showed that BPHYT_RS17700 (B2SZ63) from Burkholderia phytofirmans is required for histidine biosynthesis. PA5143 (Q9HU41) from Pseudomonas aeruginosa is required for histidine biosynthesis (PMC7028973).
- Total: 16 characterized proteins
hisC: histidinol-phosphate aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.9
- UniProt sequence HIS8_BACSU: RecName: Full=Histidinol-phosphate aminotransferase; EC=2.6.1.9; AltName: Full=Imidazole acetol-phosphate transaminase;
- UniProt sequence A0A2R7PAQ8: RecName: Full=Histidinol-phosphate aminotransferase {ECO:0000256|HAMAP-Rule:MF_01023}; EC=2.6.1.9 {ECO:0000256|HAMAP-Rule:MF_01023}; AltName: Full=Imidazole acetol-phosphate transaminase {ECO:0000256|HAMAP-Rule:MF_01023};
- UniProt sequence A0A975E8Y9: RecName: Full=Histidinol-phosphate aminotransferase {ECO:0000256|HAMAP-Rule:MF_01023}; EC=2.6.1.9 {ECO:0000256|HAMAP-Rule:MF_01023}; AltName: Full=Imidazole acetol-phosphate transaminase {ECO:0000256|HAMAP-Rule:MF_01023};
- Ignore hits to BPHYT_RS14905 when looking for 'other' hits (Aromatic-amino-acid transaminase (EC 2.6.1.57))
- Comment: In Bacillus subtilis, the histidinol-phosphate aminotransferase activity is provided by a gene that is in a cluster of genes for tyrosine and phenylalanine biosynthesis (PMID:4431). Homology suggests that this activity is provided by "HisH" (BSU22620), which indeed is just upstream of tyrA (PMID:6092865). This protein is now usually referred to as "HisC" (HIS8_BACSU). AAFF19_12795 from Acidovorax sp. FHTAMBA (nearly identical to A0A2R7PAQ8) can complement a hisC- strain of E. coli (Bradley Biggs) and is in a histidine synthesis gene cluster. AAGF34_01100 from Rhodoferax sp. GW822-FHT02A01 (similar to A0A975E8Y9) can complement a hisC- strain of E. coli (Bradley Biggs) and is in a histidine synthesis gene cluster. Fitness data for BPHYT_RS14905 from Burkholderia phytofirmans suggests that it is an aromatic amino acid transaminase, but it is 55% identical to TK06_RS12685, which can complement a hisC- mutant of E.coli (Bradley Biggs), so any similarity to it is ignored.
- Total: 1 HMMs and 22 characterized proteins
hisN: histidinol-phosphate phosphatase
- Curated proteins or TIGRFams with EC 3.1.3.15
- UniProt sequence B9E9Z0_MACCJ: RecName: Full=Histidinol-phosphatase {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003};
- UniProt sequence C0ZH63_BREBN: RecName: Full=Histidinol-phosphatase {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003};
- UniProt sequence Q73B87_BACC1: RecName: Full=Histidinol-phosphatase {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003};
- UniProt sequence A9VLI0_BACMK: RecName: Full=Histidinol-phosphatase {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003};
- UniProt sequence HIS9_BACHD: RecName: Full=Histidinol-phosphatase; Short=HolPase; EC=3.1.3.15;
- UniProt sequence Q5KW52_GEOKA: RecName: Full=Histidinol-phosphatase {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|ARBA:ARBA00013085, ECO:0000256|RuleBase:RU366003};
- UniProt sequence Q8DT80_STRMU: RecName: Full=Histidinol-phosphatase {ECO:0000256|RuleBase:RU366003}; Short=HolPase {ECO:0000256|RuleBase:RU366003}; EC=3.1.3.15 {ECO:0000256|RuleBase:RU366003};
- UniProt sequence HIS9_BACSU: RecName: Full=Histidinol-phosphatase; Short=HolPase; EC=3.1.3.15;
- UniProt sequence A0A0L7BRC5: SubName: Full=HAD family hydrolase {ECO:0000313|EMBL:KOA49733.1};
- Ignore hits to S5FT07 when looking for 'other' hits (Carbon disulfide hydrolase; CS(2) hydrolase; EC 3.13.1.5. carbon disulfide hydrolase (EC 3.13.1.5))
- Ignore hits to S5FU55 when looking for 'other' hits (Carbon disulfide hydrolase; CS(2) hydrolase; EC 3.13.1.5. carbon disulfide hydrolase (EC 3.13.1.5))
- Ignore hits to ALKAPHOSPHA-MONOMER when looking for 'other' hits (alkaline phosphatase (EC 3.1.3.1). alkaline phosphatase (EC 3.1.3.1; EC 3.1.3.75; EC 3.1.3.41; EC 3.1.3.74; EC 3.1.3.99; EC 3.1.3.5; EC 3.1.3.6; EC 3.1.3.89; EC 3.1.3.91; EC 3.1.3.60; EC 3.1.3.15; EC 3.1.3.102; EC 3.1.3.108; EC 3.1.3.11; EC 3.1.3.20; EC 3.1.3.19; EC 3.1.3.3; EC 3.6.1.25; EC 3.6.1.1; EC 3.1.3.23; EC 3.1.3.38; EC 3.1.3.18; EC 3.1.3.68; EC 3.9.1.1). alkaline phosphatase (EC 3.1.3.1; EC 3.1.3.75; EC 3.1.3.41; EC 3.1.3.74; EC 3.1.3.99; EC 3.1.3.5; EC 3.1.3.6; EC 3.1.3.89; EC 3.1.3.91; EC 3.1.3.60; EC 3.1.3.15; EC 3.1.3.102; EC 3.1.3.108; EC 3.1.3.11; EC 3.1.3.20; EC 3.1.3.19; EC 3.1.3.3; EC 3.6.1.25; EC 3.6.1.1; EC 3.1.3.23; EC 3.1.3.38; EC 3.1.3.18; EC 3.1.3.68; EC 3.9.1.1))
- UniProt sequence D4GRX2: SubName: Full=HAD superfamily hydrolase {ECO:0000313|EMBL:ADE03629.1};
- UniProt sequence A0A1I1YPH6: SubName: Full=HAD-superfamily subfamily IB hydrolase, TIGR01490 {ECO:0000313|EMBL:SFE20043.1};
- UniProt sequence A9A5X4: SubName: Full=Haloacid dehalogenase domain protein hydrolase {ECO:0000313|EMBL:ABX13452.1};
- Comment: In Bacillus subtilis and some related bacteria, histidinol-phosphate phosphatase is known as HisJ and has been confirmed by biochemical assays of purified proteins (PMC3570733). The identifiers given (see their Table 3) are MCCL_0344 BBR47_00270 BCE_1533 BcerKBAB4_1335 BcerKBAB4_1335 BSU29620 BH3206 GK2799 SMU_1486c (B9E9Z0_MACCJ C0ZH63_BREBN Q73B87_BACC1 A9VLI0_BACMK HIS9_BACHD Q5KW52_GEOKA Q8DT80_STRMU HIS9_BACSU). In Bifidobacterium breve, the phosphatase activity is provided by Bbr_0982 (A0A0L7BRC5, link). S5FT07 and S5FU55 are misannotated as this in BRENDA. E. coli phoA (link) has this activity but is ignored because it is periplasmic. HVO_0431 (D4GRX2) from Haloferax has auxotrophic phenotypes and must be the missing hisN (PMC4300041; PMC8305020). A0A1I1YPH6 ("Beta1") and Nmar_1556 (A9A5X4) were shown biochemically to be hisN (PMC10804674); Beta1 is similar to BPHYT_RS03625, which has auxotrophic phenotypes; Nmar_1556 lies in a histidine synthesis operon and must be the missing hisN.
- Total: 2 HMMs and 34 characterized proteins
hisD: histidinal/histidinol dehydrogenase
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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