Definition of D-glucosamine (chitosamine) catabolism
As rules and steps, or see full text
Rules
Overview: The canonical pathway for glucosamine utilization involves glucosamine 6-phosphate as an intermediate, as in N-acetylglucosamine utilization (link). GapMind also includes two other pathways: an oxidative pathway via glucosaminate ammonia-lyase, and a transmembrane transacetylase (NagX) pathway.
- all:
- gdh, glucosaminate-transport, glucosaminate-lyase, kdgK and kdgA
- or glucosamine-transport, glc-kinase and nagB
- or glucosamine-PTS and nagB
- or nagX and NAG-utilization
- Comment: The glucosaminate pathway begins with the periplasmic glucose dehydrogenase (gdh; PMID:1849886). (It is not clear if gdh forms glucosaminate directly or forms a lactone intermediate; the latter seems more likely but has not been demonstrated, nor has a lactonase been identified by genetics; or the lactone might hydrolyze spontaneously.) Glucosaminate is then taken up and converted to 2-keto-3-deoxygluconate by an ammonia-lyase (EC 4.3.1.9) and phosphorylated (by kdgK) to enter the Entner-Doudoroff pathway. (No phenotypes for kdgK were identified in the genetic data, but this step could be genetically redundant. It is also reported that the glucosaminate dehydratase has some aldolase activity, producing glyceraldehye and pyruvate (PMID:7766176).) Alternatively, glucosamine kinase forms glucosamine-6-phosphate, which can be converted by nagB (glucosamine 6-phosphate deaminase (isomerizing)) to fructose-6-phosphate. Glucosamine 6-phosphate can also be formed by PTS systems. Alternatively, the transmembrane transacetylase (NagX) route involves conversion in the periplasm to N-acetylglucosamine.
- 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:
- glucosamine-PTS:
- gamP
- or manX, manY and manZ
- Comment: PTS systems (forming glucosamine-6-phosphate)
- glucosaminate-transport: AO353_21715, AO353_21720, AO353_21725 and AO353_21710
- glucosamine-transport:
Steps
SM_b21216: ABC transporter for D-Glucosamine, ATPase component
- Curated sequence SM_b21216: ABC transporter for D-Glucosamine, ATPase component
- Comment: A 4-part system in Sinorhizobium meliloti was identified from genetic data; expression of this system is also induced by glucosamine or galactosamine (PMC1635973).
- Total: 1 characterized proteins
SM_b21219: ABC transporter for D-Glucosamine, permease component 1
SM_b21220: ABC transporter for D-Glucosamine, permease component 2
SM_b21221: ABC transporter for D-Glucosamine, substrate-binding protein
AO353_21715: glucosaminate ABC transporter, permease component 1
- Curated sequence AO353_21715: ABC transporter for D-glucosamine, permease component 1
- Curated sequence Pf6N2E2_2052: ABC transporter for D-Glucosamine Hydrochloride, permease component 2
- Curated sequence AO356_00475: ABC transporter for D-Glucosamine, permease component 2
- Comment: Pseudomonas oxidize glucosamine to glucosaminate using glucose dehydrogenase (PMID:1849886), which is a periplasmic enzyme. So these 4-part "glucosamine" ABC transporters, which were identified by genetic data from various Pseudomonas, are probably glucosaminate transporters
- Total: 3 characterized proteins
AO353_21720: glucosaminate ABC transporter, permease component 2
- Curated sequence AO353_21720: ABC transporter for D-glucosamine, permease component 2
- Curated sequence AO356_00470: ABC transporter for D-Glucosamine, permease component 1. ABC transporter for D-Glucosamine Hydrochloride, permease component 1
- Total: 2 characterized proteins
AO353_21725: glucosaminate ABC transporter, ATPase component
- Curated sequence AO353_21725: ABC transporter for D-glucosamine, ATPase component
- Curated sequence AO356_00465: ABC transporter for D-Glucosamine, putative ATPase component
- Curated sequence Pf6N2E2_2050: ABC transporter for D-Glucosamine, putative ATPase component
- Total: 3 characterized proteins
AO353_21710: glucosaminate ABC transporter, substrate-binding component
- Curated sequence AO353_21710: ABC transporter for D-glucosamine, periplasmic substrate-binding component
- Curated sequence AO356_00480: ABC transporter for D-Glucosamine, periplasmic substrate-binding component
- Curated sequence Pf6N2E2_2053: ABC transporter for D-Glucosamine, periplasmic substrate-binding component
- Total: 3 characterized proteins
gamP: glucosamine PTS system, EII-CBA components (GamP/NagE)
- 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 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)
- Ignore hits to P45604 when looking for 'other' hits (protein-Npi-phosphohistidine-N-acetyl-D-glucosamine phosphotransferase (EC 2.7.1.193))
- Comment: Unified EII-CBA systems from E. coli ("nagE") or B. subtilis ("gamP"). Ignore a close homolog of NagE from Klebsiella, annotated as a NAG PTS system, which is not well studied and may well act on glucosamine as well.
- Total: 2 characterized proteins
manX: glucosamine PTS system, EII-AB component ManX
- 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
- Comment: The manXYZ system from E. coli where manX has EII-AB, manY has EII-C, and manZ has EII-D. (manZ is listed twice with slightly different sequence lengths)
- Total: 1 characterized proteins
manY: glucosamine PTS system, EII-C component ManY
- 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)
- Total: 1 characterized proteins
manZ: glucosamine PTS system, EII-D component ManZ
- 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 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
- Total: 2 characterized proteins
SLC2A2: glucosamine transporter SLC2A2
- Curated sequence P11168: Solute carrier family 2, facilitated glucose transporter member 2; Glucose transporter type 2, liver; GLUT-2. Glucosamine/glucose uniporter, Glut-2; it may also transport dehydroascorbate (Mardones et al., 2011;
- Total: 1 characterized proteins
gdh: quinoprotein glucose dehydrogenase
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
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
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
glucosaminate-lyase: glucosaminate ammonia-lyase
- Curated proteins or TIGRFams with EC 4.3.1.9
- Ignore hits to Q93HX6 when looking for 'other' hits (Glucosaminate ammonia-lyase; D-glucosaminate dehydratase alpha-subunit; GlcNA-DH alpha subunit; GlcNADH-alpha; EC 4.3.1.9. glucosaminate ammonia-lyase (EC 4.3.1.9))
- Comment: A purified glucosaminate dehydratase "alpha subunit" was determined to be thioredoxin (SwissProt Q93HX6), which seems unlikely to physiologically relevant.
- Total: 5 characterized proteins
kdgK: 2-keto-3-deoxygluconate kinase
- Curated proteins or TIGRFams with EC 2.7.1.45
- Curated proteins or TIGRFams with EC 2.7.1.178
- Ignore hits to Q9ZU29 when looking for 'other' hits (2-dehydro-3-deoxyglucono/galactono-kinase (EC 2.7.1.178))
- Ignore hits to DEHYDDEOXGALACTKIN-MONOMER when looking for 'other' hits (2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178; EC 2.7.1.58). 2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178))
- Comment: The entry for Q9ZU29 is erroneous (the correct accession is Q97U29). EcoCyc 2-dehydro-3-deoxygalactonokinase (dgoK) is given this EC number as well but I could not determine why. It doesn't link to the ketodeoxygluconate kinase reaction.
- Total: 14 characterized proteins
kdgA: 2-keto-3-deoxygluconate-6-phosphate aldolase EC:4.1.2.14
glc-kinase: glucosamine kinase
- Curated proteins or TIGRFams with EC 2.7.1.8
- Curated proteins or TIGRFams with EC 2.7.1.147
- UniProt sequence Q92VI2: SubName: Full=Sugar amine kinase {ECO:0000313|EMBL:CAC49121.1}; EC=2.7.1.- {ECO:0000313|EMBL:CAC49121.1};
- Comment: Fitness data confirms that SM_b21217 (Q92VI2), a proposed glucosamine kinase, is involved in glucosamine utilization.
- Total: 13 characterized proteins
nagX: transmembrane glucosamine N-acetyltransferase NagX
- UniProt sequence A0KZW6: RecName: Full=DUF5009 domain-containing protein {ECO:0000259|Pfam:PF16401};
- UniProt sequence A1S448: RecName: Full=DUF5009 domain-containing protein {ECO:0000259|Pfam:PF16401};
- UniProt sequence L0FVP4: RecName: Full=DUF1624 domain-containing protein {ECO:0000259|Pfam:PF07786};
- Comment: These NagX proteins are distantly related to human HGSNAT (Q68CP4), which is a transmembrane acetyl-CoA:alpha-glucosaminide N-acetyltransferase. Genetic data suggests that these bacterial homologs are involved in glucosamine utilization, but not as a transporter -- N-acetylglucosamine utilization genes are also involved. So, they appear to be transmembrane N-acetyltransferases for glucosamine. The key histidine which holds the acetyl group as it passes through the membrane (His269 in NG_009552.1, or His297 in Q68CP4) is conserved in these proteins. The bacterial proteins with clear evidence for this role are: Shewana3_3111 (A0KZW6), Sama_0947 (A1S448), and Echvi_1106 (L0FVP4).
- Total: 3 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