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
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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