As text, or see rules and steps
# In most bacteria, glucose is consumed via glucose 6-phosphate, which is a
# central metabolic intermediate.
# It can also be oxidized to 2-ketogluconate in the periplasm before uptake
# and conversion to gluconate 6-phosphate (metacyc:DHGLUCONATE-PYR-CAT-PWY).
# Periplasmic oxidation to gluconate, uptake, and phosphorylation by gnuK is also
# a potential path to gluconate-6-phosphate, but is not included in GapMind because it is not known to be
# the major path for glucose utilization in a prokaryote.
# Monomeric or homomeric transporters:
# MFS superfamily glucose transporters include:
# glcP, O07563 (glcP from B. subtilis), SLCA14/Q8TDB8,
# ght/rgt, SLC2A10, GT4, GTR6, gluP, and
# singletons Q04DP6 Q04FN1 CH_091224 CH_091141 P21906 Q8IRI6 C5DX43.
# Also add the hexose transporters HXT7_YEAST / P39004, CharProtDB::CH_091031 (nearly identical).
# Ignore CharProtDB::CH_091031 which is nearly identical to G4N740.
# Add P43581, yet another yeast glucose transporter.
# Ignore CH_122303, yet another hexose transporter.
# Ignore yet more yeast hexose transporters P40886, P54862, GHT8_SCHPO / Q9P3U7, C5E4Z7,
# CH_123252, CH_123250, CH_122864, P39924, CH_124796, P54854.
# Shewana3_2310 = glcP(Mal) = A0KXM0 was shown to be a glucose transporter (PMID:20836887).
MFS-glucose glucose transporter, MFS superfamily curated:SwissProt::A0A0H2VG78 curated:CharProtDB::CH_091029 curated:CharProtDB::CH_091305 curated:CharProtDB::CH_091400 curated:CharProtDB::CH_091463 curated:CharProtDB::CH_091493 curated:CharProtDB::CH_091695 curated:CharProtDB::CH_122958 curated:CharProtDB::CH_124310 curated:SwissProt::A0A1D8PCL1 curated:SwissProt::F1R0H0 curated:SwissProt::O44616 curated:SwissProt::O44827 curated:SwissProt::P0AEP1 curated:SwissProt::P11166 curated:SwissProt::P11167 curated:SwissProt::P11168 curated:SwissProt::P11169 curated:SwissProt::P12336 curated:SwissProt::P14142 curated:SwissProt::P14246 curated:SwissProt::P14672 curated:SwissProt::P17809 curated:SwissProt::P19357 curated:SwissProt::P27674 curated:SwissProt::P32037 curated:SwissProt::P47843 curated:SwissProt::P58353 curated:SwissProt::P58354 curated:SwissProt::Q07647 curated:SwissProt::Q56ZZ7 curated:SwissProt::Q9JIF3 curated:SwissProt::Q9JJZ1 curated:SwissProt::Q9NY64 curated:SwissProt::Q9WV38 curated:SwissProt::Q9XSC2 curated:TCDB::A0QZX3 curated:TCDB::A0ZXK6 curated:TCDB::A1Z264 curated:TCDB::G4N740 curated:TCDB::H9BPB6 curated:TCDB::P15729 curated:TCDB::P23585 curated:TCDB::P49374 curated:TCDB::Q0SE66 curated:TCDB::Q2MDH1 curated:TCDB::Q2MEV7 curated:TCDB::Q63ZP5 curated:TCDB::Q7BEC4 curated:TCDB::Q8G3X1 curated:TCDB::Q8J0U9 curated:TCDB::Q8NTX0 curated:TCDB::Q9LT15 curated:SwissProt::O07563 curated:SwissProt::Q8TDB8 curated:CharProtDB::CH_091552 curated:CharProtDB::CH_121984 curated:SwissProt::P22732 curated:SwissProt::P43427 curated:SwissProt::P46408 curated:SwissProt::Q3T9X0 curated:SwissProt::Q6PXP3 curated:SwissProt::Q9BYW1 curated:SwissProt::Q9NRM0 curated:TCDB::Q26579 curated:TCDB::A3M0N3 curated:CharProtDB::CH_091058 curated:CharProtDB::CH_123257 curated:SwissProt::B8MYS7 curated:SwissProt::P32465 curated:SwissProt::P32466 curated:TCDB::Q9P3U6 curated:SwissProt::O95528 curated:SwissProt::Q5J316 curated:SwissProt::Q6NWF1 curated:SwissProt::Q8BFW9 curated:SwissProt::Q8TD20 curated:TCDB::B1PLM1 curated:TCDB::O61059 curated:TCDB::O61060 curated:TCDB::O76486 curated:TCDB::Q06222 curated:TCDB::A5Y0C3 curated:SwissProt::Q3UDF0 curated:SwissProt::Q9UGQ3 curated:TCDB::O25788 curated:TCDB::P0C105 curated:TCDB::Q04DP6 curated:TCDB::Q04FN1 curated:CharProtDB::CH_091224 curated:CharProtDB::CH_091141 curated:SwissProt::P21906 curated:SwissProt::Q8IRI6 curated:TCDB::C5DX43 curated:TCDB::P39004 curated:CharProtDB::CH_091031 ignore:CharProtDB::CH_091031 curated:TCDB::P43581 ignore:CharProtDB::CH_122303 ignore:SwissProt::P40886 ignore:TCDB::P54862 ignore:SwissProt::Q9P3U7 ignore:TCDB::C5E4Z7 ignore:CharProtDB::CH_123252 ignore:CharProtDB::CH_123250 ignore:CharProtDB::CH_122864 ignore:TCDB::P39924 ignore:CharProtDB::CH_124796 ignore:TCDB::P54854 uniprot:A0KXM0
# solute_symporter (SSS) family transpoters
SSS-glucose Sodium/glucose cotransporter curated:SwissProt::A0PJK1 curated:CharProtDB::CH_091086 curated:SwissProt::P11170 curated:SwissProt::P31636 curated:SwissProt::P31639 curated:SwissProt::P96169 curated:SwissProt::Q28610 curated:SwissProt::Q28728 curated:SwissProt::Q2M3M2 curated:SwissProt::Q6R4Q5 curated:SwissProt::Q8K0E3 curated:SwissProt::Q8WWX8 curated:SwissProt::Q9NY91 curated:SwissProt::Q9Z1F2 curated:TCDB::P26430 curated:TCDB::Q2A687
# Named glcU' in GapMind to distinguish from an ABC transporter component named glcU
glcU' Glucose uptake protein GlcU curated:SwissProt::O07881 curated:SwissProt::P40420 curated:TCDB::L8DP77 curated:TCDB::Q9CDF7
PAST-A proton-associated sugar transporter A curated:SwissProt::Q8K4S3 curated:TCDB::Q9Y2W3
# Ignore some uncharacterized homologs:
# SwissProt::B0SR19,
# TCDB::Q8F4F7,
# SwissProt::P0DMV3 (structure is known; transports sucrose poorly; physiological substrate unclear),
# TCDB::A2BS89,
# TCDB::Q57574 ("LbSemiSWEET"; has glucose transport activity, but not clear if it is the physiological substrate).
SemiSWEET Sugar transporter SemiSWEET curated:SwissProt::B0SR19 ignore:TCDB::Q8F4F7 ignore:SwissProt::P0DMV3 ignore:TCDB::A2BS89 ignore:TCDB::Q57574
SWEET1 bidirectional sugar transporter SWEET1 curated:SwissProt::Q8L9J7
# This has a high Km, ignore
# SWEET1 Sweet1 glucose/galactose facilitator (Km ≥ 50mM) Caenorhabditis elegans;; Caenorhabditis elegans
# From gene expression only, I think, so ignore
# Singleton 5 CharProtDB::CH_124119 high-affinity glucose transporter Magnaporthe grisea 70-15
# Singleton 6 CharProtDB::CH_124120 high-affinity glucose transporter RGT2 Magnaporthe grisea 70-15
# Singleton 7 CharProtDB::CH_124123 low-affinity glucose transporter HXT1 Magnaporthe grisea 70-15
# Ignore porins and various regulators and efflux systems
# ABC transporters:
# mglABC-like ABC transporters, from E. coli, Haloferax, Thermotoga, Agrobacterium, and Phaeobacter.
# But in Haloferax, only two components are known; there is a SBP nearby but also a second permease.
# So mark TSGDD_HALVD / D4GPW3 and D4GPW2 as ignore.
# Also, there is one paper about the Salmonella ortholog of mglABC; not clear if that transports
# glucose or not, so ignore that as well (P23924).
mglA glucose ABC transporter, ATP-binding component (MglA) ignore:SwissProt::D4GPW3 curated:TCDB::G4FGN3 curated:TCDB::O05176 curated:TCDB::P0AAG8 curated:reanno::Phaeo:GFF3641 ignore:SwissProt::P23924
# mglB (b2150) from E. coli (P0AEE5; 332 a.a.),
# chvE, or TC 3.A.1.2.20 / G4FGN5 in Thermotoga (343 a.a.)
# [absent from Haloferax].
# Ignore SBPA_AZOBR / P54083 from Azospirillum, whose substrate specificity is uncertain.
mglB glucose ABC transporter, substrate-binding component curated:TCDB::P0AEE5 curated:TCDB::P25548 curated:reanno::Phaeo:GFF3639 curated:TCDB::G4FGN5 ignore:SwissProt::P54083
# mglC (b2148) and related proteins, and a protein from Haloferax (TSGBD_HALVD / D4GPW2; TSGDD_HALVD / D4GPW3)
mglC glucose ABC transporter, permease component (MglC) curated:TCDB::G4FGN4 curated:TCDB::P23200 curated:TCDB::O05177 curated:reanno::Phaeo:GFF3640 ignore:SwissProt::D4GPW2
# gtsABCD-like ABC transporters, from Thermus, Pseudomonas putida, and Pseudomonas fluorescens GW456-L13.
# (Some components cluster with glcSTUV from Saccharolobus, which is described separately;
# those are marked ignore here.)
# The system in P. fluorescens is very similar (~90% a.a. identity) to PS417_22145:PS417_22130 (GFF4324:GFF4321),
# which is involved in glucose-6-phosphate utilization, probably as a glucose transporter.
# Fitness data also identified a gtsABCD-like glucose transporter in Acidovorax sp. GW101-3H11
# (Ac3H11_2062:Ac3H11_2064:Ac3H11_2065:Ac3H11_2066; A0A165KPY4, A0A165KPZ4, A0A165KQ00, A0A165KQ08).
gtsA glucose ABC transporter, substrate-binding component (GtsA) curated:TCDB::Q88P38 curated:TCDB::Q72KX2 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1894 curated:reanno::WCS417:GFF4324 uniprot:A0A165KPY4
gtsB glucose ABC transporter, permease component 1 (GtsB) curated:TCDB::Q88P37 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1895 curated:TCDB::Q72KX3 curated:reanno::WCS417:GFF4323 uniprot:A0A165KPZ4
gtsC glucose ABC transporter, permease component 2 (GtsC) curated:TCDB::Q72KX4 curated:TCDB::Q88P36 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1896 curated:reanno::WCS417:GFF4322 uniprot:A0A165KQ00
gtsD glucose ABC transporter, ATPase component (GtsD) curated:TCDB::Q72L52 ignore:BRENDA::Q97UY8 curated:TCDB::Q88P35 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1897 curated:reanno::WCS417:GFF4321 uniprot:A0A165KQ08
# ABC transporter glcSTUV from Saccharolobus/Sulfolobus
glcS glucose ABC transporter, substrate-binding component (GlcS) curated:SwissProt::Q97UZ1
glcT glucose ABC transporter, permease component 1 (GlcT) curated:TCDB::Q97UZ0
glcU glucose ABC transporter, permease component 2 (GlcU) curated:TCDB::Q97UY9
glcV glucose ABC transporter, ATPase component (GclV) curated:BRENDA::Q97UY8
# ABC transporter aglEFGK (Dshi_1652:Dshi_1648) from Dinoroseobacter shibae.
# The gene names are from the related system aglEFGK of Sinorhizobium meliloti,
# which are involved in uptake of sucrose and some other disaccharides (PMID:10400573).
# In fitness data, S. meliloti aglEFGK are important for maltose & trehalose utilization (see SMc03061 = aglE);
# they are not important on glucose but S. meliloti also has SM_b20894, which is similar to gguA/mglA O05176.
# It is uncertain whether aglEFGK from S. meliloti can transport glucose or not, so it is ignored.
# Dshi_1652 = A8LLL6.
aglE' glucose ABC transporter, substrate-binding component (AglE) uniprot:A8LLL6 ignore:reanno::Smeli:SMc03061
# Dshi_1651 = A8LLL5.
aglF' glucose ABC transporter, permease component 1 (AglF) uniprot:A8LLL5 ignore:reanno::Smeli:SMc03062
# Dshi_1650 = A8LLL4.
aglG' glucose ABC transporter, permease component 2 (AglG) uniprot:A8LLL4 ignore:reanno::Smeli:SMc03063
# Dshi_1648 = A8LLL2.
aglK' glucose ABC transporter, ATPase component (AglK) uniprot:A8LLL2 ignore:reanno::Smeli:SMc03065
# Transporters and PTS systems were analyzed uzing
# query: transporter:glucose:D-glucose:D-glucopyranose:ALPHA-GLUCOSE:GLC:CPD-15374
glucose-transport: MFS-glucose
glucose-transport: SSS-glucose
glucose-transport: glcU'
glucose-transport: PAST-A
glucose-transport: SemiSWEET
glucose-transport: SWEET1
glucose-transport: mglA mglB mglC
glucose-transport: gtsA gtsB gtsC gtsD
glucose-transport: glcS glcT glcU glcV
glucose-transport: aglE' aglF' aglG' aglK'
# PTS systems, forming glucose-6-phosphate:
# Fused (one-component) PTS system, EIICBA (ptsG in B. subtilis; two systems from Staphylococcus)
ptsG-crr glucose PTS, enzyme II (CBA components, PtsG) curated:CharProtDB::CH_001857 curated:SwissProt::Q53922 curated:SwissProt::Q57071
# Another one-component PTS system, bglF from E. coli
bglF glucose PTS, enzyme II (BCA components, BglF) curated:TCDB::P08722
# PTS system EII-CB (ptsG) and EII-A (crr), in E. coli and Salmonella
# EII-CB proteins.
# Ignore O51590 (4.A.1.1.18) from Borrelia burgdorferi, which is not characterized and the EIIA component is uncertain.
# Ignore E. coli malX (P19642), which facilitates diffusion of glucose (no phosphorylation);
# its physiological function is unclear so it is not listed as a sole glucose transporter.
# Ignore PTUCB_KLEPN / Q9AGA7 from Klebsiella, as the EII-A component was not described
ptsG glucose PTS, enzyme IICB ignore:SwissProt::Q9AGA7 curated:BRENDA::P69786 curated:SwissProt::P37439 ignore:TCDB::O51590 ignore:TCDB::P19642
# Ignore a close homlog in Serratia (TC 4.A.3.2.5 / Q8L3C4) which is reported to be the II-A component
# for N,N' -diacetylchitobiose (probably shared with other sugars).
crr glucose PTS, enzyme IIA curated:CharProtDB::CH_088352 curated:SwissProt::P0A283 ignore:TCDB::Q8L3C4
# PTS system manXYZ (manX is EIIAB; manY is EIIC; manZ is EIID)
# from E. coli, Listeria, Oenococcus, Lactobacillus, and Streptococcus.
# Systems related to manXYZ in Streptococcus salivarius and Lactococcus lactis subsp. lactis are
# reported to act on glucose, but are listed with other preferred substrates; ignore these.
manX glucose PTS, enzyme EIIAB curated:CharProtDB::CH_088329 curated:TCDB::E1UCI0 curated:TCDB::Q04GK1 curated:TCDB::Q2QKM4 curated:TCDB::Q5M5W6 ignore:BRENDA::Q9S4L5 ignore:TCDB::D2BKY7
# Also similar is Lmo0782 (TC 4.A.6.1.16 / Q8Y8W0) from MpoABCD, a PTS-like glucose sensor;
# this is not ignored but possibly should be.
manY glucose PTS, enzyme EIIC curated:CharProtDB::CH_088330 curated:TCDB::E1UCI1 curated:TCDB::Q04GK0 curated:TCDB::Q2QKM3 curated:TCDB::Q5M5W7
# (The E. coli entry, P69805, is listed twice, because the sequence in TCDB has 3 extra N-terminal residues.)
# Also similar is Lmo0781 (TC 4.A.6.1.16 / Q8Y8W1) from MpoABCD; should perhaps be ignored.
manZ glucose PTS, enzyme EIID curated:SwissProt::P69805 curated:TCDB::E1UCI2 curated:TCDB::P69805 curated:TCDB::Q04GJ9 curated:TCDB::Q2QKM2 curated:TCDB::Q5M5W8 ignore:BRENDA::Q5IRC0 ignore:TCDB::D2BKY9
glucose-PTS: ptsG-crr
glucose-PTS: bglF
glucose-PTS: ptsG crr
glucose-PTS: manX manY manZ
# Dshi_1655 (A8LLL9) was identified using fitness data, is very important for growth on glucose and
# several glucose-containing disaccharides; and functional residues seem to be conserved.
# The related protein PGA1_c05420 (I7DXX1) also seems to be glk.
# Q5GAN8 = hexA from B. fragilis is a broad-specificity hexokinase (PMID:15659667).
# Q5GBH5 = rokA = MONOMER-19002 from B. fragilis is a glucose/mannose/NAG kinase (PMID:15659667).
# (MetaCyc lists it as NAG kinase only but it is just as active on glucose.)
# CH_123431 is nearly identical to a characterized broad-specificity hexose kinase, so ignore.
# SCO5059 (Q9ADE8) is reported to have ATP-glucokinase activity (PMID:24200789), so ignore.
glk glucokinase EC:2.7.1.1 EC:2.7.1.2 uniprot:A8LLL9 uniprot:Q5GAN8 curated:metacyc::MONOMER-19002 ignore:CharProtDB::CH_123431 ignore:BRENDA::Q9ADE8 uniprot:I7DXX1
gdh quinoprotein glucose dehydrogenase EC:1.1.5.2
# Add Pseudomonas ppgL (PA4204 = Q9HWH7; see PMID:18832304)
gnl gluconolactonase EC:3.1.1.17 uniprot:Q9HWH7
# gluconate 2-dehydrogenase has three subunits; known in Pseudomonas fluorescens and Pantoea/Pectobacterium cypripedii.
# There's also papers about two different enzymes in Gluconobacter.
# PMID:17720837 describes A4PIA9 = gndS = gadh3; A4PIB0 = gndL = gadh1; A4PIB1 = gndC = gadh2;
# BRENDA includes only A4PIB0.
# PMID:27392695 shows that overexpressing GOX1232 to GOX1230 (Q5FRK3 G5EBD9 Q5FRK5), paralogs of gndSLC,
# leads to increased production of 2-ketogluconate; BRENDA includes only Q5FRK5.
# Finally, C0LE03 is listed by BRENDA as a gluconate 2-dehydrogenase and is nearly identical to
# Q4KKM7 = metacyc:MONOMER-12745, so include that as well.
# Some papers also mention GOX0147 = 5FTU6 but that is the cytoplasmic 2-ketogluconate reductase.
gadh1 gluconate 2-dehydrogenase flavoprotein subunit curated:SwissProt::O34214 curated:metacyc::MONOMER-12745 curated:BRENDA::A4PIB0 uniprot:G5EBD9 curated:BRENDA::C0LE03
gadh2 gluconate 2-dehydrogenase cytochrome c subunit curated:SwissProt::O34215 curated:metacyc::MONOMER-12746 uniprot:A4PIB1 curated:BRENDA::Q5FRK5
gadh3 gluconate 2-dehydrogenase subunit 3 curated:SwissProt::O34213 curated:metacyc::MONOMER-12747 uniprot:A4PIA9 uniprot:Q5FRK3
# kguT = KU168042 = A0A167V864 was shown to be required for 2-ketogluconate utilization (PMID:30109560)
kguT 2-ketogluconate transporter uniprot:A0A167V864
kguK 2-ketogluconokinase EC:2.7.1.13
kguD 2-keto-6-phosphogluconate reductase EC:1.1.1.43
edd phosphogluconate dehydratase EC:4.2.1.12
eda 2-keto-3-deoxygluconate 6-phosphate aldolase EC:4.1.2.14 EC:4.1.2.55
# Glucose can be taken up and then phosphorylated to glucose 6-phosphate by the kinase glk.
glucose-utilization: glucose-transport glk
# Or, both uptake and phosphorylation are catalyzed by a PTS system.
glucose-utilization: glucose-PTS
# Or, glucose is oxidized to glucono-1,5-lactone in the periplasm (by gdh),
# hydrolyzed to gluconate (by gnl), oxidized to 2-ketogluconate (by gadh123),
# taken up by kguT, phosphorylated to 2-dehydro-6-phosphogluconate (by kguK),
# reduced to gluconate 6-phosphate (by kguD), dehydrated by edd to
# 2-dehydro-3-deoxy-gluconate 6-phosphate, and cleaved by aldolase eda
# to pyruvate and D-glyceraldehyde 3-phosphate.
glucose-utilization: gdh gnl gadh1 gadh2 gadh3 kguT kguK kguD edd eda
all: glucose-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