As text, or see rules and steps
# Mannose utilization in GapMind is based on MetaCyc pathways # D-mannose degradation I via a PTS system (metacyc:MANNCAT-PWY), # pathway II via mannose kinase (metacyc:PWY3O-1743), # or conversion to fructose by mannose isomerase. # PTS systems # 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. manX mannose PTS system, EII-AB component ManX/ManL curated:CharProtDB::CH_088329 curated:TCDB::D2BKY7 curated:TCDB::E1UCI0 ignore:TCDB::Q5M5W6 ignore:BRENDA::Q9S4L5 ignore:TCDB::Q04GK1 ignore:TCDB::Q2QKM4 manY mannose PTS system, EII-C component ManY/ManM curated:CharProtDB::CH_088330 curated:TCDB::D2BKY8 curated:TCDB::E1UCI1 ignore:TCDB::Q5M5W7 ignore:TCDB::Q8Y8W0 ignore:TCDB::Q04GK0 ignore:TCDB::Q2QKM3 manZ mannose PTS system, EII-D component ManZ/ManN curated:SwissProt::P69805 curated:TCDB::D2BKY9 curated:TCDB::E1UCI2 curated:TCDB::P69805 ignore:TCDB::Q5M5W8 ignore:TCDB::Q04GJ9 ignore:TCDB::Q2QKM2 ignore:BRENDA::Q5IRC0 ignore:TCDB::Q8Y8W1 # PTS systems form D-mannose 6-phosphate mannose-PTS: manX manY manZ # B. subtilis has a combined EII-BCA PTS system manP mannose PTS system, EII-CBA components curated:BRENDA::O31645 mannose-PTS: manP # ABC transporters are described in Saccharolobus solfataricus (formerly Sulfolobus), # Thermus thermophilus, Thermotoga maritima, # and Ensifer meliloti (formerly Rhizobium or Sinorhizobium); and # fitness data identified a system in Herbaspirillum seropedicae. # The Saccharolobus solfataricus system (4 components) glcS mannose ABC transporter, substrate-binding component GlcS curated:SwissProt::Q97UZ1 glcT mannose ABC transporter, permease component 1 (GlcT) curated:TCDB::Q97UZ0 glcU mannose ABC transporter, permease component 2 (GlcU) curated:TCDB::Q97UY9 glcV mannose ABC transporter, ATPase component GlcV curated:BRENDA::Q97UY8 # Transporters and PTS systems were identified using # query: transporter:mannose:D-mannose:D-mannopyranose:CPD-13559:CPD-12601 mannose-transport: glcS glcT glcU glcV # The Thermus thermophilus system (4 components) TT_C0211 mannose ABC transporter, ATPase component MalK1 curated:TCDB::Q72L52 TT_C0327 mannose ABC transporter, permease component 1 curated:TCDB::Q72KX3 TT_C0326 mannose ABC transporter, permease component 2 curated:TCDB::Q72KX4 TT_C0328 mannose ABC transporter, substrate-binding component curated:TCDB::Q72KX2 mannose-transport: TT_C0211 TT_C0327 TT_C0326 TT_C0328 # The Thermotoga maritima system (5 components) TM1746 mannose ABC transporter, substrate-binding component curated:TCDB::Q9X268 TM1747 mannose ABC transporter, permease component 1 curated:TCDB::Q9X269 TM1748 mannose ABC transporter, permease component 2 curated:TCDB::Q9X270 TM1749 mannose ABC transporter, ATPase component 1 curated:TCDB::Q9X271 TM1750 mannose ABC transporter, ATPase component 2 curated:TCDB::Q9X272 mannose-transport: TM1746 TM1747 TM1748 TM1749 TM1750 # The Ensifer meliloti system (3 components) frcA mannose ABC transporter, ATPase component FrcA curated:SwissProt::Q9F9B0 frcB mannose ABC transporter, substrate-binding component FrcB curated:SwissProt::Q9F9B2 frcC mannose ABC transporter, permease component FrcC curated:SwissProt::Q9F9B1 mannose-transport: frcA frcB frcC # The Herbaspirillum seropedicae system (3 components) HSERO_RS03635 mannose ABC transporter, substrate-binding component uniprot:D8IZC6 HSERO_RS03640 mannose ABC transporter, ATPase component uniprot:D8IZC7 HSERO_RS03645 mannose ABC transporter, permease component uniprot:D8IZC8 mannose-transport: HSERO_RS03635 HSERO_RS03640 HSERO_RS03645 # Homomeric transporters: STP6 mannose:H+ symporter curated:CharProtDB::CH_091493 curated:TCDB::Q9LT15 mannose-transport: STP6 gluP mannose:Na+ symporter curated:TCDB::O25788 curated:reanno::SB2B:6936374 mannose-transport: gluP glcP mannose:H+ symporter curated:SwissProt::O07563 mannose-transport: glcP MST1 mannose:H+ symporter curated:TCDB::A0ZXK6 mannose-transport: MST1 manMFS mannose transporter, MFS superfamily curated:reanno::pseudo5_N2C3_1:AO356_28540 mannose-transport: manMFS # Ignore Snf3p (TCDB::Q06222 2.A.1.1.18) which has a regulatory role # SMc03111 (P29954) is specifically important for utilizing mannose, # which confirms it is mannose 6-phosphate isomerase manA mannose-6-phosphate isomerase EC:5.3.1.8 uniprot:P29954 # 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. all: mannose-PTS manA # Ignore some vaguely annotated mannose or mannose-6-phosphate isomerases man-isomerase D-mannose isomerase EC:5.3.1.7 ignore:reanno::pseudo3_N2E3:AO353_03400 ignore:reanno::pseudo1_N1B4:Pf1N1B4_597 ignore:reanno::pseudo5_N2C3_1:AO356_05200 # 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) mannokinase D-mannose kinase EC:2.7.1.7 curated:reanno::Smeli:SMc03109 curated:metacyc::MONOMER-19002 uniprot:Q5GAN8 # In pathway II, after uptake, mannose kinase is followed by isomerization to fructose 6-phosphate. all: mannose-transport mannokinase manA import fructose.steps:scrK # fructokinase # Or, D-mannose isomerase yields # fructose, which can be metabolized by fructokinase (scrK). all: mannose-transport man-isomerase scrK
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:
Otherwise, a candidate is "medium confidence" if either:
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:
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