Definition of N-acetyl-D-glucosamine catabolism
As rules and steps, or see full text
Rules
Overview: N-acetylglucosamine utilization in GapMind is based on MetaCyc pathways N-acetylglucosamine degradation I (link) and pathway II (link). These pathways differ in whether uptake and phosphorylation are performed by a PTS system or performed separately by a transporter and a kinase.
- all: NAG-utilization
- NAG-utilization:
- NAG-PTS, nagA and nagB
- or NAG-transport, nagK, nagA and nagB
- Comment: Both pathways involve N-acetylglucosamine 6-phosphate, followed by deacetylase nagA and the isomerizing deaminase nagB, which produces fructose 6-phosphate, a central metabolic intermediate.
- NAG-transport:
- NAG-PTS:
Steps
nagEcba: N-acetylglucosamine phosphotransferase system, EII-CBA components
- Curated sequence P09323: protein-Npi-phosphohistidine-N-acetyl-D-glucosamine phosphotransferase (EC 2.7.1.193). PTS system N-acetylglucosamine-specific EIICBA component; EIICBA-Nag; EII-Nag; EC 2.7.1.193. N-Acetyl glucosamine (NAG) porter (NagE). N-acetylglucosamine-specific PTS enzyme IIABC component (EC 2.7.1.193; EC 2.7.1.191). N-acetylglucosamine-specific PTS enzyme IIABC component (EC 2.7.1.193; EC 2.7.1.191)
- Curated sequence P45604: protein-Npi-phosphohistidine-N-acetyl-D-glucosamine phosphotransferase (EC 2.7.1.193)
- Comment: unified EII-ABC (as in E. coli and Klebsiella pneumoniae)
- Total: 2 characterized proteins
nagF: N-acetylglucosamine phosphotransferase system, E-I, Hpr, and EII-A components (NagF)
- Curated sequence BPHYT_RS02740: N-acetylglucosamine-specific PTS system, I, HPr, and IIA components (nagF)
- Curated sequence AO353_04460: N-acetylglucosamine-specific PTS system, I, HPr, and IIA components (nagF)
- Curated sequence AO356_17540: N-acetylglucosamine-specific PTS system, I, HPr, and IIA components (nagF)
- Curated sequence Q9HXN5: N-Acetyl-D-Glucosamine phosphotransferase system transporter, component of N-acetyl glucosamine-specific PTS permease, GlcNAc IIBC/GlcNAc I-HPr-IIA
- Comment: nagFE, where nagF has PTS I, Hpr, and II-A, and nagE has II-CB (in Burkholderia phytofirmans and two Pseudomonas fluorescens, and in P. aeruginosa)
- Total: 4 characterized proteins
nagEcb: N-acetylglucosamine phosphotransferase system, EII-CB components
- Curated sequence BPHYT_RS02745: N-acetylglucosamine-specific PTS system, IIBC components (nagE)
- Curated sequence AO353_04465: N-acetylglucosamine-specific PTS system, IIBC components (nagE)
- Curated sequence AO356_17535: N-acetylglucosamine-specific PTS system, IIBC components (nagE)
- Curated sequence Q9HXN4: N-Acetyl-D-Glucosamine phosphotransferase system transporter, component of N-acetyl glucosamine-specific PTS permease, GlcNAc IIBC/GlcNAc I-HPr-IIA
- Total: 4 characterized proteins
crr: N-acetylglucosamine phosphotransferase system, EII-A component Crr
- UniProt sequence Q9KZP2: SubName: Full=Putative PTS system sugar phosphotransferase component IIA {ECO:0000313|EMBL:CAB88886.1};
- Comment: Streptomyces coelicolor has just EII-B and EII-C (ptsB, ptsC); "crr" (SCO1390 or Q9KZP2) is the EII-A (see PMC3294797). Streptomyces olivaceoviridis has a related system with EII-B, EII-C, and EII-C' components (ptsBC1C2). Did not find any papers about the EII-A component in S. olivaceoviridis.
- Total: 1 characterized proteins
ptsB: N-acetylglucosamine-specific phosphotransferase system, EII-B component PtsB
- Curated sequence Q9S2H6: PTS system N-acetylglucosamine-specific EIIB component; PTS system GlcNAc-specific EIIB component; N-acetylglucosamine-specific phosphotransferase enzyme IIB component; GlcNAc-specific phosphotransferase enzyme IIB component; EC 2.7.1.193
- Curated sequence Q8GBT8: IIB aka PtsB, component of N-Acetylglucosamine (NAG) porter (PtsBC1C2)(also may facilitate xylose transport)
- Total: 2 characterized proteins
ptsC: N-acetylglucosamine phosphotransferase system, EII-C component PtsC
- Curated sequence Q9S2H4: PTS system N-acetylglucosamine-specific EIIC component; PTS system GlcNAc-specific EIIC component; GlcNAc-specific transporter; N-acetylglucosamine permease IIC component; GlcNAc permease IIC component
- Curated sequence Q8GBT6: IIC' aka PtsC2, component of N-Acetylglucosamine (NAG) porter (PtsBC1C2)(also may facilitate xylose transport)
- Comment: In S. olivaceoviridis, either ptsC1 or ptsC2 suffices for xylose uptake, but ptsC2 is specific for NAG (PMID:12436256), so include ptsC2 here. Not sure if ptsC1 = Q8GBT7 should be marked ignore or not.
- Total: 2 characterized proteins
nagEIIA: N-acetylglucosamine phosphotransferase system, EII-A component (PtsG/YpqE/GamP)
- Curated sequence P20166: PTS system glucose-specific EIICBA component; EC 2.7.1.-; EC 2.7.1.69. The glucose IICBA porter (PtsG) 44% identical to 4.A.1.1.1)
- UniProt sequence P50829: RecName: Full=Putative phosphotransferase enzyme IIA component YpqE; AltName: Full=Putative PTS system EIIA component;
- Curated sequence P39816: Putative PTS system glucosamine-specific EIICBA component; EC 2.7.1.193. The glucosamine IICBA porter (GamP) (40% identical to 4.A.1.1.2) (Plumbridge 2015). The IIA domain in this protein can transfer the phosphoryl moiety to the maltose, N-acetylglucosamine, sucrose and trehalose PTS systems (MalP, NagP, SacP and TreP, respectively)
- Comment: Bacillus subtilis has EII-CB, known as nagP. The major EII-A is ptsG (P20166, see PMID:30038046), which is a bit surprising as ptsG has EII-B and EII-C domains as well and is thought to be specific for glucose; YpqE (P50829) or GamP (P39816) also suffice. (YpqE has EII-A only, while GamP is the EII-CBA protein for glucosamine)
- Total: 3 characterized proteins
nagPcb: N-acetylglucosamine phosphotransferase system, EII-CB component NagP
- Curated sequence O34521: PTS system N-acetylglucosamine-specific EIICB component; EIICB-Nag; EC 2.7.1.-. The N-acetylglucosamine IICB porter (NagP; YflF) (45% identical to 4.A.1.1.2)
- Total: 1 characterized proteins
SMc02869: N-acetylglucosamine ABC transporter, ATPase component
- Curated sequence GFF2754: N-Acetyl-D-glucosamine ABC transport system, ATPase component
- Curated sequence SMc02869: N-Acetyl-D-glucosamine ABC transport system, ATPase component
- Comment: Phaeobacter inhibens and Sinorhizobium meliloti have a 4-component system; name them by the S. meliloti components
- Total: 2 characterized proteins
SMc02872: N-acetylglucosamine ABC transporter, permease component 1
- Curated sequence GFF2751: N-Acetyl-D-glucosamine ABC transport system, permease component 1
- Curated sequence SMc02872: ABC transporter for N-Acetyl-D-glucosamine, permease protein 1
- Total: 2 characterized proteins
SMc02871: N-acetylglucosamine ABC transporter, permease component 2
- Curated sequence GFF2752: N-Acetyl-D-glucosamine ABC transport system, permease component 2
- Curated sequence SMc02871: ABC transporter for N-Acetyl-D-glucosamine, permease protein 2
- Total: 2 characterized proteins
SMc02873: N-acetylglucosamine ABC transporter, substrate-binding component
- Curated sequence GFF2750: N-Acetyl-D-glucosamine ABC transport system, periplasmic substrate-binding component
- Curated sequence SMc02873: N-Acetyl-D-glucosamine ABC transport system, periplasmic substrate-binding component
- Total: 2 characterized proteins
ngcE: N-acetylglucosamine ABC transporter, substrate-binding component (NgcE)
- Curated sequence Q8RJV0: NgcE, component of N-Acetylglucosamine/N,N'-diacetyl chitobiose porter (NgcK (C) not identified)
- Comment: Streptomyces olivaceoviridis has ngcEFG, with the presumed ATPase component not identified. It probably depends on a shared ATPase component such as msiK (known in S. coelicolor)
- Total: 1 characterized proteins
ngcF: N-acetylglucosamine ABC transporter, permease component 1 (NgcF)
- Curated sequence Q8RJU9: NgcF, component of N-Acetylglucosamine/N,N'-diacetyl chitobiose porter (NgcK (C) not identified)
- Total: 1 characterized proteins
ngcG: N-acetylglucosamine ABC transporter, permease component 2 (NgcG)
- Curated sequence Q8RJU8: NgcG, component of N-Acetylglucosamine/N,N'-diacetyl chitobiose porter (NgcK (C) not identified)
- Total: 1 characterized proteins
nagP: N-acetylglucosamine transporter NagP
- Curated sequence Q8EBL0: N-acetylglucosamine porter, NagP. N-acetyl glucosamine transporter, NagP
- Curated sequence 7025962: N-acetylglucosamine transporter nagP
- Total: 2 characterized proteins
nag3: N-acetylglucosamine transporter nag3/nag4
- Curated sequence A0A1D8PQG0: Major facilitator superfamily multidrug transporter NAG3; Multidrug resistance protein 97; N-acetylglucosamine utilization protein 3; Transmembrane protein 1
- Curated sequence Q59RG0: Major facilitator superfamily multidrug transporter NAG4; N-acetylglucosamine utilization protein 4; Transmembrane protein 2. potential polyamine transporter
- Total: 2 characterized proteins
ngt1: N-acetylglucosamine:H+ symporter Ngt1
nagA: N-acetylglucosamine 6-phosphate deacetylase
- Curated proteins or TIGRFams with EC 3.5.1.25
- Ignore hits to CH_123434 when looking for 'other' hits (predicted N-acetylglucosamine-6-phosphate deacetylase)
- Comment: Ignore a putative NAG deacetylase from C. albicans, not given this EC number, in CharProtDB
- Total: 1 HMMs and 27 characterized proteins
nagB: glucosamine 6-phosphate deaminase (isomerizing)
- Curated proteins or TIGRFams with EC 3.5.99.6
- Curated sequence CH_123433: glucosamine-6-phosphate deaminase
- UniProt sequence Q92VI1: RecName: Full=Glutamine--fructose-6-phosphate aminotransferase [isomerizing] {ECO:0000256|ARBA:ARBA00016090}; EC=2.6.1.16 {ECO:0000256|ARBA:ARBA00012916};
- Comment: Add the Candida isomerase, not given this EC number by CharProtDB. And fitness data confirms the proposal that SM_b21218 (Q92VI1) is this enzyme.
- Total: 1 HMMs and 25 characterized proteins
nagK: N-acetylglucosamine kinase
- Curated proteins or TIGRFams with EC 2.7.1.59
- Ignore hits to CH_123431 when looking for 'other' hits (N-acetylglucosamine kinase)
- UniProt sequence Q8P6S9: SubName: Full=Glucose kinase {ECO:0000313|EMBL:AAM42158.1};
- UniProt sequence Q8P6M4: SubName: Full=Glucose kinase {ECO:0000313|EMBL:AAM42215.1};
- Comment: Ignore a putative enzyme from C. albicans, not given this EC number in CharProtDB. PMC2832512 identified two NAG kinases in Xanthomonas campestris, XCC2886 (Q8P6S9) and XCC2943 (Q8P6M4)
- Total: 18 characterized proteins
Links
Downloads
Related tools
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