As text, or see rules and steps
# Many bacteria take up fructose by a phosphotransferase (PTS) system # that forms fructose 1-phosphate; this can be consumed via 1-phosphofructokinase # and glycolysis (metacyc:PWY0-1314). # Alternatively, some PTS systems form fructose 6-phosphate, which is # a central metabolic intermediate. # Fructose can also be taken up directly and then phosphorylated to # fructose 6-phosphate, a central metabolic intermediate. # Another path is known in Aeromonas hydrophila -- phosphofructomutase # converts fructose 1-phosphate (formed by a PTS system) to fructose # 6-phosphate (PMID:9579084). This path is not included in GapMind because # phosphofructomutase has not been linked to sequence. # Also, in eukaryotes, fructose-1,6-bisphosphate aldolase is reported # to cleave fructose 1-phosphate to glycerone phosphate and glyceraldehyde # (metacyc:PWY66-373). This would make 1-phosphofructokinase # unnececessary. It's not clear that this occurs in prokaryotes, so # this is not listed. # Two classes of phosphotransferase systems: # PTS 4.A.2.* produce fructose 1-phosphate, while other PTS produce fructose 6-phosphate # FruA/FruB: # E. coli: FruA has EII-B'BC # FruB includes E-IIA and also an HPr domain # Also a paralogous system frvAB, TC 4.A.2.1.25 (P32154,P32155), but it is not actually characterized # Deinococcus radiodurans has FruA-like II-BC; the adjacent II-A is a pseudogene, but it still functions, # apparently by an as-yet unknown cytoplasmic ATP-driven component. # (For now, just annotate it as another fruA) # FruA/FruI, where FruI has I-Hpr-IIA components # P. aeruginosa has FruA and "FruI" # Azospirillum brasilense: FruA = uniprot:G8B0J2 (not yet reannotated) and FruI = AZOBR_RS32325 # (curated, but definition line does not mention fructose, so was not originally included) # Xanthomonas campestris: FruA = P23355 and FruI = XCC2370 = P45597 fruA fructose-specific PTS system (fructose 1-phosphate forming), EII-B'BC components curated:BRENDA::Q8DWE7 curated:SwissProt::P20966 curated:SwissProt::P23355 ignore:TCDB::P32154 curated:TCDB::Q9HY57 curated:TCDB::Q9RZP7 uniprot:G8B0J2 # Homologs of fruB from Salmonella typhimurium and Haemophilus influenzae probably have the # same function, but are annotated differently in SwissProt. fruB fructose-specific PTS system (fructose 1-phosphate forming), Hpr and EII-A components curated:SwissProt::P69811 ignore:SwissProt::P17127 ignore:SwissProt::P44715 # Homologs of fruI in other Pseudomonas fluorescens are annotated differently, but # are important for fructose utilization, so probably have the same function. fruI fructose-specific PTS system (fructose 1-phosphate forming), EI, Hpr, and EII-A components curated:TCDB::Q9HY55 curated:reanno::azobra:AZOBR_RS32325 curated:reanno::pseudo3_N2E3:AO353_05485 curated:SwissProt::P45597 curated:reanno::pseudo1_N1B4:Pf1N1B4_1146 curated:reanno::pseudo5_N2C3_1:AO356_07335 curated:reanno::WCS417:GFF780 curated:reanno::psRCH2:GFF3291 # Streptococcus mutans has FruA-like "FruC" plus "FruD" with EII-A only. fruD fructose-specific PTS system (fructose 1-phosphate forming), EII-A component curated:BRENDA::Q8DWE6 # Fructose 1-phosphate forming PTS systems contain FruA with either FruB, FruI, or FruD. # FruA has EII-B'BC components; the other genes all have E-IIA but their domain content varies. # FruB has E-IIA and Hpr components; FruI has EI-Hpr-IIA components; and FruD has E-IIA only. fructose-PTS-1-phosphate: fruA fruB fructose-PTS-1-phosphate: fruA fruI fructose-PTS-1-phosphate: fruA fruD # 3-part PTS system (fructose 1-phosphate forming) in Haloferax volcanii, Haloterrigena turkmenica, Haloarcula marismortui. # The Haloarcula gene cluster also includes enzyme I (ptsI, Q5V5X2) and HPr (ptsH, Q5V5X3), # which is not represented here fruII-A fructose-specific PTS system (fructose 1-phosphate forming), EII-A component curated:TCDB::D2RXA7 curated:SwissProt::D4GYE4 curated:TCDB::Q5V5X4 fruII-B fructose-specific PTS system (fructose 1-phosphate forming), EII-B component curated:SwissProt::D4GYE1 curated:TCDB::D2RXA4 curated:TCDB::Q5V5X1 fruII-C fructose-specific PTS system (fructose 1-phosphate forming), EII-C component curated:SwissProt::D4GYE5 curated:TCDB::D2RXA8 curated:TCDB::Q5V5X5 fructose-PTS-1-phosphate: fruII-A fruII-B fruII-C # Spiroplasma citri has a unified PTS system E-IIABC which clustered with fruA above but is distantly related # The others were in cluster 4 fruII-ABC fructose-specific PTS system (fructose 1-phosphate forming), EII-ABC components curated:TCDB::Q9RMF5 curated:TCDB::Q3K0G6 curated:TCDB::P71012 curated:TCDB::Q0S1N2 curated:TCDB::Q1LZ59 fructose-PTS-1-phosphate: fruII-ABC # Fructose 6-phosphate forming PTS systems, which are all of the "mannose" type # and have an additional EII-D component. # B. subtilis has 4 components (levDEFG, also known as ptfABCD) # while in E. coli, Oneococcus oeni, and Streptococcus thermophilus, the EII-AB components are fused levD fructose PTS system (fructose 6-phosphate forming), EII-A component curated:SwissProt::P26379 levE fructose PTS system (fructose 6-phosphate forming), EII-B component curated:SwissProt::P26380 # uniprot:Q9S4L5 is nearly identical to uniprot:Q5M5W6; not sure if it acts on fructose or not. # uniprot:D2BKY7 is very similar to uniprot:Q5M5W6 and has been studied mostly as a receptor to bacteriocins; not # sure if it acts on fructose or not. levDE fructose PTS system (fructose 6-phosphate forming), EII-AB component curated:CharProtDB::CH_088329 curated:TCDB::Q04GK1 curated:TCDB::Q5M5W6 ignore:BRENDA::Q9S4L5 ignore:TCDB::D2BKY7 levF fructose PTS system (fructose 6-phosphate forming), EII-C component curated:CharProtDB::CH_088330 curated:TCDB::P26381 curated:TCDB::Q04GK0 curated:TCDB::Q5M5W7 # Ignore SwissProt::P69805 which is nearly identical to P69805. # Ignore Q5IRC0, whose specificity is unknown. levG fructose PTS system (fructose 6-phosphate forming), EII-D component curated:TCDB::P26382 curated:TCDB::P69805 curated:TCDB::Q04GJ9 curated:TCDB::Q5M5W8 ignore:SwissProt::P69805 ignore:BRENDA::Q5IRC0 fructose-PTS-6-phosphate: levD levE levF levG fructose-PTS-6-phosphate: levDE levF levG # ABC type transporters # AraSUTV from Sulfolobus solfataricus araV fructose ABC transporter, ATPase component AraV curated:TCDB::Q97UF2 araU fructose ABC transporter, permease component 1 (AraU) curated:TCDB::Q97UF3 araT fructose ABC transporter, permease component 2 (AraT) curated:TCDB::Q97UF4 araS fructose ABC transporter, substrate-binding component AraS curated:TCDB::Q97UF5 # Transporters and PTS systems (forming -1-phosphate or -6-phosphate) were found using # query: transporter:fructose:D-fructose:BETA-D-FRUCTOSE. fructose-transport: araV araU araT araS # FruEFGK from Bifidobacterium longum. # (FruF is distantly related to frcC, which is described separately) fruE fructose ABC transporter, substrate-binding component FruE curated:SwissProt::Q8G848 fruF fructose ABC transporter, permease component 1 (FruF) curated:SwissProt::Q8G846 fruG fructose ABC transporter, permease component 2 (FruG) curated:SwissProt::Q8G845 fruK fructose ABC transporter, ATPase component FruK curated:SwissProt::Q8G847 fructose-transport: fruE fruF fruG fruK # FrcABC from Rhizobium meliloti. # A distantly related system in Ralstonia eutropha H16 is required for fructose utilization (PMID:21478317), # and fitness data confirms that the homologs in Cupriavidus basilensis 4G11 are # important during growth on fructose # (frcA = RR42_RS03360 = A0A0C4Y5F6; frcC = RR42_RS03365 = A0A0C4Y7K0; frcB = RR42_RS03370 = A0A0C4Y591) frcA fructose ABC transporter, ATPase component FrcA curated:SwissProt::Q9F9B0 uniprot:A0A0C4Y5F6 frcB fructose ABC transporter, substrate-binding component FrcB curated:SwissProt::Q9F9B2 uniprot:A0A0C4Y591 frcC fructose ABC transporter, permease component FrcC curated:SwissProt::Q9F9B1 uniprot:A0A0C4Y7K0 fructose-transport: frcA frcB frcC # Homomeric transporters: # Ignore Q6PXP3 (GTR7_HUMAN) as there is debate as to its activity Slc2a5 fructose:H+ symporter curated:TCDB::A0ZXK6 curated:CharProtDB::CH_091463 curated:SwissProt::P22732 curated:SwissProt::P43427 curated:SwissProt::P46408 curated:SwissProt::P58353 ignore:SwissProt::Q6PXP3 curated:SwissProt::Q9WV38 curated:TCDB::Q9XIH7 fructose-transport: Slc2a5 ffz fructose facilitator (uniporter) curated:TCDB::C5DX43 curated:TCDB::C5E4Z7 curated:TCDB::Q70WR7 fructose-transport: ffz glcP fructose:H+ symporter GlcP curated:TCDB::P15729 curated:reanno::Korea:Ga0059261_1777 fructose-transport: glcP ght6 high-affinity fructose transporter ght6 curated:CharProtDB::CH_091085 fructose-transport: ght6 STP6 sugar transport protein 6 curated:CharProtDB::CH_091493 fructose-transport: STP6 THT2A fructose THT2A curated:TCDB::Q06222 fructose-transport: THT2A frt1 fructose:H+ symporter Frt1 curated:TCDB::Q8NJ22 fructose-transport: frt1 # N515DRAFT_1918 (A0A1I2JXG1) from Dyella japonica UNC79MFTsu3.2 is an MFS-type transporter that is # specifically important for growth on fructose. fruP fructose porter FruP uniprot:A0A1I2JXG1 fructose-transport: fruP # The putative hexose transporter BT1758 (Q8A6W8) is important for fructose and levan utilization # It is in a fructan utilization cluster, so was propsoed to be the fructose transporter (see PMC3225772) BT1758 fructose transporter uniprot:Q8A6W8 fructose-transport: BT1758 # Ignore CharProtDB::CH_122687, potential proton-coupled fructose symporter from Candida albicans, # not actually characterized # Ignore the fructose porin (TCDB::Q51485, 1.B.19.1.1) from Pseudomonas aeruginosa # For a PTS forming fructose 6-phosphate, no further steps are needed to reach # central metabolism. fructose-utilization: fructose-PTS-6-phosphate # ignore fragmentary sequence of Q09123 scrK fructokinase EC:2.7.1.4 ignore:SwissProt::Q09123 # For direct transport, the usual pathway is fructokinase (scrK), forming fructose 6-phosphate. fructose-utilization: fructose-transport scrK 1pfk 1-phosphofructokinase EC:2.7.1.56 # Ignore several fragmentary sequences, and CH_091808 seems to be misannotated with another EC number # Q5SJM8 is nearly identical to Q72K02, a bifunctional aldolase/phosphatase, but is annotated only as phosphatase fba fructose 1,6-bisphosphate aldolase EC:4.1.2.13 ignore:SwissProt::P84722 ignore:SwissProt::P86979 ignore:SwissProt::P86980 ignore:CharProtDB::CH_091808 ignore:BRENDA::Q5SJM8 # Ignore a fragmentary (allergen) sequence tpi triose-phosphate isomerase EC:5.3.1.1 ignore:SwissProt::P85814 # For PTS forming fructose 1-phosphate, the usual path is phosphorylation (1pfk) and # cleavage by fructose 1,6-bisphosphate aldolase (fba); triose-phosphate isomerase (tpi) # converts the glycerone phosphate to D-glyceraldehyde 3-phosphate, which is # a central metabolic intermediate. fructose-utilization: fructose-PTS-1-phosphate 1pfk fba tpi all: fructose-utilization
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