Definition of D-mannose catabolism
As rules and steps, or see full text
Rules
Overview: Mannose utilization in GapMind is based on MetaCyc pathways D-mannose degradation I via a PTS system (link), pathway II via mannose kinase (link), or conversion to fructose by mannose isomerase.
- all:
- mannose-PTS and manA
- or mannose-transport, mannokinase and manA
- or mannose-transport, man-isomerase and scrK
- Comment: In pathway I, after uptake and phosphorlation by a PTS system, mannose-6-phosphate isomerase (manA) produces fructose-6-phosphate, which is a central metabolic intermediate. In pathway II, after uptake, mannose kinase is followed by isomerization to fructose 6-phosphate. Or, D-mannose isomerase yields fructose, which can be metabolized by fructokinase (scrK).
- mannose-transport:
- mannose-PTS:
Steps
manX: mannose PTS system, EII-AB component ManX/ManL
- Curated sequence CH_088329: PTS system mannose-specific EIIAB component; EC 2.7.1.-; EC 2.7.1.69. PTS system mannose-specific EIIAB component; EIIAB-Man; EIII-Man; EC 2.7.1.191. PTNA aka MANX aka PTSL aka GPTB aka B1817, component of The mannose (glucose, 2-deoxyglucose, glucosamine, N-acetylglucosamine, N-acetylmannosamine, mannosamine and fructose) PTS porter/group translocator, ManXYZ (Rephaeli and Saier 1980; Plumbridge 2015). Catalyzes xylose facilitated diffusion in lactobacilli. The order of D-sugar substrate affinities is: glucose > mannose > 2-deoxyglucose > N-acetylglucosamine > glucosamine > N-acetylmannosamine > mannosamine > fructose. mannose-specific PTS enzyme IIAB component (EC 2.7.1.191; EC 2.7.1.199; EC 2.7.1.193). mannose-specific PTS enzyme IIAB component
- Curated sequence D2BKY7: Mannose-specificPTS system, IIAB component, component of Mannose enzyme II complex, IIAB, IIC, IID. IIC/IID serve allows entry of some bacteriocins including pediocin (class IIa) and lactococcin A (class IIc) (Kjos et al., 2011). Transports and phosphorylates Glucose, Mannose and Glucosamine
- Curated sequence E1UCI0: PTS system, mannose-specific, IIAB component, component of The primary glucose /mannose uptake transporter, ManLMN
- Ignore hits to Q5M5W6 when looking for 'other' hits (ManL, component of The glucose/mannose/2-deoxyglucose/fructose phosphotransferase systems (phosphorylates without transport), ManLMN)
- Ignore hits to Q9S4L5 when looking for 'other' hits (protein-Npi-phosphohistidine-D-mannose phosphotransferase (EC 2.7.1.191))
- Ignore hits to Q04GK1 when looking for 'other' hits (Phosphotransferase system, mannose/fructose-specific component IIA, component of The hexose (glucose and fructose demonstrated) PTS uptake system)
- Ignore hits to Q2QKM4 when looking for 'other' hits (ManL aka EIIAB, component of Glucose porter, ManLMN)
- Comment: E. coli has manXYZ, where manX has EII-AB, manY has EII-C, and manZ has EII-D. (ManZ is listed twice with slightly different sequence lengths). Similar systems are known in Lactococcus lactis, Listeria monocytogenes, and Streptococcus thermophilus. However, the S. thermophilus system seems not to be active due to a defective IIC domain (PMID:12957931), so those proteins are marked ignore. L. monocytogenes also has a PTS-like regulatory system, mpoABCD, which is not included. (It is reported to act as a glucose transporter, but slowly; not clear if it transports mannose.) There's also a paper about manLMN from Streptococcus salivarius, but I don't think it is actually characterized, so ignore. Closely related to some systems with unclear specificity, ignore those.
- Total: 3 characterized proteins
manY: mannose PTS system, EII-C component ManY/ManM
- Curated sequence CH_088330: mannose permease IIC component. PTS system mannose-specific EIIC component; EII-P-Man; EIIC-Man; Mannose permease IIC component. PTNC aka MANY aka PTSP aka PEL aka B1818, component of The mannose (glucose, 2-deoxyglucose, glucosamine, N-acetylglucosamine, N-acetylmannosamine, mannosamine and fructose) PTS porter/group translocator, ManXYZ (Rephaeli and Saier 1980; Plumbridge 2015). Catalyzes xylose facilitated diffusion in lactobacilli. The order of D-sugar substrate affinities is: glucose > mannose > 2-deoxyglucose > N-acetylglucosamine > glucosamine > N-acetylmannosamine > mannosamine > fructose. mannose-specific PTS enzyme IIC component (EC 2.7.1.191; EC 2.7.1.199; EC 2.7.1.193). mannose-specific PTS enzyme IIC component (EC 2.7.1.191; EC 2.7.1.199; EC 2.7.1.193)
- Curated sequence D2BKY8: Mannose-specific PTS system, IIC component, component of Mannose enzyme II complex, IIAB, IIC, IID. IIC/IID serve allows entry of some bacteriocins including pediocin (class IIa) and lactococcin A (class IIc) (Kjos et al., 2011). Transports and phosphorylates Glucose, Mannose and Glucosamine
- Curated sequence E1UCI1: PTS system, mannose/fructose/sorbose family, IIC component, component of The primary glucose /mannose uptake transporter, ManLMN
- Ignore hits to Q5M5W7 when looking for 'other' hits (ManM, component of The glucose/mannose/2-deoxyglucose/fructose phosphotransferase systems (phosphorylates without transport), ManLMN)
- Ignore hits to Q8Y8W0 when looking for 'other' hits (Lmo0782 protein, component of Constitutively synthesized sensor, MpoABCD, controlling man operon (see TC# 4.A.6.1.15) expression by interacting with and phosphorylating ManR, the transcriptional regulator of the man operon)
- Ignore hits to Q04GK0 when looking for 'other' hits (Mannose-specific PTS system component IIC, component of The hexose (glucose and fructose demonstrated) PTS uptake system)
- Ignore hits to Q2QKM3 when looking for 'other' hits (ManM aka EIIC, component of Glucose porter, ManLMN)
- Total: 3 characterized proteins
manZ: mannose PTS system, EII-D component ManZ/ManN
- Curated sequence P69805: PTS system mannose-specific EIID component; EII-M-Man; EIID-Man; Mannose permease IID component. mannose-specific PTS enzyme IID component (EC 2.7.1.191; EC 2.7.1.199; EC 2.7.1.193). mannose-specific PTS enzyme IID component (EC 2.7.1.191; EC 2.7.1.199; EC 2.7.1.193)
- Curated sequence D2BKY9: Mannose-specific PTS system, IID component, component of Mannose enzyme II complex, IIAB, IIC, IID. IIC/IID serve allows entry of some bacteriocins including pediocin (class IIa) and lactococcin A (class IIc) (Kjos et al., 2011). Transports and phosphorylates Glucose, Mannose and Glucosamine
- Curated sequence E1UCI2: PTS system, mannose/fructose/sorbose family, IID component, component of The primary glucose /mannose uptake transporter, ManLMN
- Curated sequence P69805: PTND aka MANZ aka PTSM aka GPTB aka B1819, component of The mannose (glucose, 2-deoxyglucose, glucosamine, N-acetylglucosamine, N-acetylmannosamine, mannosamine and fructose) PTS porter/group translocator, ManXYZ (Rephaeli and Saier 1980; Plumbridge 2015). Catalyzes xylose facilitated diffusion in lactobacilli. The order of D-sugar substrate affinities is: glucose > mannose > 2-deoxyglucose > N-acetylglucosamine > glucosamine > N-acetylmannosamine > mannosamine > fructose
- Ignore hits to Q5M5W8 when looking for 'other' hits (ManN, component of The glucose/mannose/2-deoxyglucose/fructose phosphotransferase systems (phosphorylates without transport), ManLMN)
- Ignore hits to Q04GJ9 when looking for 'other' hits (PTS system IID component, Man family, component of The hexose (glucose and fructose demonstrated) PTS uptake system)
- Ignore hits to Q2QKM2 when looking for 'other' hits (ManN aka EIID, component of Glucose porter, ManLMN)
- Ignore hits to Q5IRC0 when looking for 'other' hits (protein-Npi-phosphohistidine-D-mannose phosphotransferase (EC 2.7.1.191))
- Ignore hits to Q8Y8W1 when looking for 'other' hits (Lmo0781 protein, component of Constitutively synthesized sensor, MpoABCD, controlling man operon (see TC# 4.A.6.1.15) expression by interacting with and phosphorylating ManR, the transcriptional regulator of the man operon)
- Total: 4 characterized proteins
manP: mannose PTS system, EII-CBA components
- Curated sequence O31645: protein-Npi-phosphohistidine-D-mannose phosphotransferase (EC 2.7.1.191). PTS system mannose-specific EIIBCA component; EIIBCA-Man; EII-Man; EC 2.7.1.191. The mannose porter (ManP) (37% identical to 4.A.2.1.1). It is encoded in an operon with 3 genes:
- Comment: B. subtilis has a combined EII-BCA PTS system
- Total: 1 characterized proteins
glcS: mannose ABC transporter, substrate-binding component GlcS
- Curated sequence Q97UZ1: Glucose-binding protein GlcS; GBP. GlcS, component of Glucose, mannose, galactose porter
- Comment: The Saccharolobus solfataricus system (4 components)
- Total: 1 characterized proteins
glcT: mannose ABC transporter, permease component 1 (GlcT)
glcU: mannose ABC transporter, permease component 2 (GlcU)
glcV: mannose ABC transporter, ATPase component GlcV
- Curated sequence Q97UY8: monosaccharide-transporting ATPase (EC 3.6.3.17). Glucose import ATP-binding protein GlcV; EC 7.5.2.-. GlcV, component of Glucose, mannose, galactose porter
- Total: 1 characterized proteins
TT_C0211: mannose ABC transporter, ATPase component MalK1
- Curated sequence Q72L52: Sugar-binding transport ATP-binding protein aka MalK1 aka TT_C0211, component of The trehalose/maltose/sucrose/palatinose porter (TTC1627-9) plus MalK1 (ABC protein, shared with 3.A.1.1.24) (Silva et al. 2005; Chevance et al., 2006). The receptor (TTC1627) binds disaccharide alpha-glycosides, namely trehalose (alpha-1,1), sucrose (alpha-1,2), maltose (alpha-1,4), palatinose (alpha-1,6) and glucose
- Comment: The Thermus thermophilus system (4 components)
- Total: 1 characterized proteins
TT_C0327: mannose ABC transporter, permease component 1
- Curated sequence Q72KX3: Glucose transport system permease protein aka TT_C0327, component of The glucose/mannose porter TTC0326-8 plus MalK1 (ABC protein, shared with 3.A.1.1.25)
- Total: 1 characterized proteins
TT_C0326: mannose ABC transporter, permease component 2
- Curated sequence Q72KX4: Sugar transport system permease protein aka TT_C0326, component of The glucose/mannose porter TTC0326-8 plus MalK1 (ABC protein, shared with 3.A.1.1.25)
- Total: 1 characterized proteins
TT_C0328: mannose ABC transporter, substrate-binding component
- Curated sequence Q72KX2: Glucose-binding protein aka TT_C0328, component of The glucose/mannose porter TTC0326-8 plus MalK1 (ABC protein, shared with 3.A.1.1.25)
- Total: 1 characterized proteins
TM1746: mannose ABC transporter, substrate-binding component
- Curated sequence Q9X268: TM1746, component of Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR
- Comment: The Thermotoga maritima system (5 components)
- Total: 1 characterized proteins
TM1747: mannose ABC transporter, permease component 1
- Curated sequence Q9X269: TM1747, component of Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR
- Total: 1 characterized proteins
TM1748: mannose ABC transporter, permease component 2
- Curated sequence Q9X270: TM1748, component of Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR
- Total: 1 characterized proteins
TM1749: mannose ABC transporter, ATPase component 1
- Curated sequence Q9X271: TM1749, component of Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR
- Total: 1 characterized proteins
TM1750: mannose ABC transporter, ATPase component 2
- Curated sequence Q9X272: TM1750, component of Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR
- Total: 1 characterized proteins
frcA: mannose ABC transporter, ATPase component FrcA
- Curated sequence Q9F9B0: Fructose import ATP-binding protein FrcA; EC 7.5.2.-. FrcA, component of Fructose/mannose/ribose porter
- Comment: The Ensifer meliloti system (3 components)
- Total: 1 characterized proteins
frcB: mannose ABC transporter, substrate-binding component FrcB
frcC: mannose ABC transporter, permease component FrcC
HSERO_RS03635: mannose ABC transporter, substrate-binding component
- UniProt sequence D8IZC6: SubName: Full=ABC-type sugar transport system, periplasmic component protein {ECO:0000313|EMBL:ADJ62246.1};
- Comment: The Herbaspirillum seropedicae system (3 components)
- Total: 1 characterized proteins
HSERO_RS03640: mannose ABC transporter, ATPase component
- UniProt sequence D8IZC7: RecName: Full=Ribose import ATP-binding protein RbsA {ECO:0000256|HAMAP-Rule:MF_01716}; EC=7.5.2.7 {ECO:0000256|HAMAP-Rule:MF_01716};
- Total: 1 characterized proteins
HSERO_RS03645: mannose ABC transporter, permease component
- UniProt sequence D8IZC8: SubName: Full=ABC-type sugar transport system, permease component protein {ECO:0000313|EMBL:ADJ62248.1};
- Total: 1 characterized proteins
STP6: mannose:H+ symporter
- Curated sequence CH_091493: sugar transport protein 6. Sugar transport protein 6; Hexose transporter 6. High affinity monosaccharide (KM ≈ 20 µM):H+ symporter, Stp6 (takes up glucose, 3-O-methylglucose, mannose, fructose, galactose and to a lesser extent, xylose and ribulose.
- Curated sequence Q9LT15: The high affinity sugar:H+ symporter (sugar uptake) porter of 514 aas and 12 TMSs, STP10. It transports glucose, galactose and mannose, and is therefore a hexose transporter (Rottmann et al. 2016). The 2.4
- Total: 2 characterized proteins
gluP: mannose:Na+ symporter
- Curated sequence O25788: The Na+-dependent sugar transporter, HP1174 (transports glucose, galactose, mannose and 2-deoxyglucose (Psakis et al. 2009)). (most similar to 2.A.1.7.2; 49% identity)
- Curated sequence 6936374: D-mannitol and D-mannose transporter (MFS superfamily)
- Total: 2 characterized proteins
glcP: mannose:H+ symporter
- Curated sequence O07563: Glucose/mannose transporter GlcP; Glucose/mannose:H(+) symporter. Glucose/Mannose/Xylose: H+ symporter (Paulsen et al., 1998; G.Gosset, personal communication)
- Total: 1 characterized proteins
MST1: mannose:H+ symporter
manMFS: mannose transporter, MFS superfamily
manA: mannose-6-phosphate isomerase
- Curated proteins or TIGRFams with EC 5.3.1.8
- UniProt sequence P29954: RecName: Full=Mannose-6-phosphate isomerase; EC=5.3.1.8; AltName: Full=Phosphohexomutase; AltName: Full=Phosphomannose isomerase; Short=PMI;
- Comment: SMc03111 (P29954) is specifically important for utilizing mannose, which confirms it is mannose 6-phosphate isomerase
- Total: 1 HMMs and 29 characterized proteins
man-isomerase: D-mannose isomerase
- Curated proteins or TIGRFams with EC 5.3.1.7
- Ignore hits to AO353_03400 when looking for 'other' hits (Isomerase for D-mannose and D-mannitol catabolism (probably D-mannose-6-phosphate isomerase or D-mannose isomerase))
- Ignore hits to Pf1N1B4_597 when looking for 'other' hits (Isomerase for D-mannose and D-mannitol catabolism (probably D-mannose-6-phosphate or D-mannose isomerase))
- Ignore hits to AO356_05200 when looking for 'other' hits (Isomerase for D-mannose and D-mannitol catabolism (probably D-mannose-6-phosphate isomerase or D-mannose isomerase))
- Comment: Ignore some vaguely annotated mannose or mannose-6-phosphate isomerases
- Total: 7 characterized proteins
mannokinase: D-mannose kinase
- Curated proteins or TIGRFams with EC 2.7.1.7
- Curated sequence SMc03109: Mannokinase (EC 2.7.1.7)
- Curated sequence MONOMER-19002: N-acetylglucosamine kinase (EC 2.7.1.59)
- UniProt sequence Q5GAN8: SubName: Full=General specificity hexokinase {ECO:0000313|EMBL:AAT74901.1};
- Comment: SMc03109 was annotated as mannokinase but not given this EC number. rokA (MONOMER-19002) and hexA (Q5GAN8) are hexose kinases, including mannose kinases (PMID:PMC545704)
- Total: 7 characterized proteins
scrK: fructokinase
- Curated proteins or TIGRFams with EC 2.7.1.4
- Ignore hits to Q09123 when looking for 'other' hits (Fructokinase; EC 2.7.1.4)
- Comment: ignore fragmentary sequence of Q09123
- Total: 36 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