Finding step hisN for L-histidine biosynthesis in Malonomonas rubra DSM 5091
Known gap: Despite the apparent lack of hisN, Malonomonas rubra DSM 5091 performs L-histidine biosynthesis.
2 candidates for hisN: histidinol-phosphate phosphatase
Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway
GapMind searches the predicted proteins for candidates by using ublast (a fast alternative to protein BLAST) to find similarities to characterized proteins or by using HMMer to find similarities to enzyme models (usually from TIGRFams). For alignments to characterized proteins (from ublast), scores of 44 bits correspond to an expectation value (E) of about 0.001.
Definition of step hisN
- Curated proteins or TIGRFams with EC 3.1.3.15 (search)
- 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.
Or cluster all characterized hisN proteins
Known gaps in related organisms
This GapMind analysis is from Jul 25 2024. The underlying query database was built on Jul 25 2024.
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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