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# Galactose utilization in GapMind is based on MetaCyc pathways # lactose and galactose degradation I via tagatose 6-phosphate (metacyc:LACTOSECAT-PWY), # the Leloir pathway via UDP-galactose (metacyc:PWY-6317), # and the oxidative pathway via D-galactonate (metacyc:GALDEG-PWY). # Pathway IV via galactitol (metacyc:PWY-6693) is not reported in prokaryotes and is not included. # (There is no pathway III.) # ABC transporters # Escherichia coli has a 3-part system (mglABC) and a 4-part system (ytfQTR-yjtF) # Salmonella typhimurium also has mglABC; but only mglA is listed mglA galactose ABC transporter, ATPase component MglA curated:TCDB::P0AAG8 curated:SwissProt::P23924 mglB galactose ABC transporter, substrate-binding component MglB curated:TCDB::P0AEE5 mglC galactose ABC transporter, permease component MglC curated:TCDB::P23200 # Transporters and PTS systems were identified using: # query: transporter:galactose:D-galactose:D-galactofuranose:D-galactopyranose:CPD0-2486:CPD0-2485:alpha-d-galactose:CPD-15590 galactose-transport: mglA mglB mglC ytfQ galactose ABC transporter, substrate-binding component curated:SwissProt::P39325 ytfR galactose ABC transporter, ATPase component curated:ecocyc::YTFR-MONOMER ytfT galactose ABC transporter, permease component 1 curated:SwissProt::P39328 yjtF galactose ABC transporter, permease component 2 curated:SwissProt::P37772 galactose-transport: ytfQ ytfR ytfT yjtF # Agrobacterium tumefaciens / radiobacter has a 3-part transporter (GguAB-ChvE, also known as CVE1) gguA galactose ABC transporter, ATPase component GguA curated:TCDB::O05176 gguB galactose ABC transporter, permease component GguB curated:TCDB::O05177 # SbpA from Azospirillum brasilense (P543083) is involved in chemotaxis towards galactose, and could well # be part of a galactose transport system chvE galactose ABC transporter, substrate-binding component ChvE curated:TCDB::P25548 ignore:SwissProt::P54083 galactose-transport: gguA gguB chvE # Sulfolobus (Saccharolobus) solfataricus has a 4-part transporter glcSTUV glcS galactose ABC transporter, substrate-binding component GlcS curated:SwissProt::Q97UZ1 glcT galactose ABC transporter, permease component 1 (GlcT) curated:TCDB::Q97UZ0 glcU galactose ABC transporter, permease component 2 (GlcU) curated:TCDB::Q97UY9 glcV galactose ABC transporter, ATPase component (GlcV) curated:BRENDA::Q97UY8 galactose-transport: glcS glcT glcU glcV # Pseudomonas fluorescens has a 4-part transporter. # A related system in P. simiae WCS417 is slightly deleterious during growth on galactose, # so it could be a galactose transporter; it is marked ignore. # A related system is also found in P. putida (gtsABCD), which does not utilize galactose, # but similar systems in other Pseudomonas do seem to be involved in galactose transport # (i.e., AO356_05195:AO356_05180 from FW300-N2C3), so gtsABCD is also marked ignore.. PfGW456L13_1894 ABC transporter for D-Galactose and D-Glucose, periplasmic substrate-binding component curated:reanno::pseudo13_GW456_L13:PfGW456L13_1894 ignore:reanno::WCS417:GFF4324 ignore:TCDB::Q88P38 PfGW456L13_1895 ABC transporter for D-Galactose and D-Glucose, permease component 1 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1895 ignore:reanno::WCS417:GFF4323 ignore:TCDB::Q88P37 PfGW456L13_1896 ABC transporter for D-Galactose and D-Glucose, permease component 2 curated:reanno::pseudo13_GW456_L13:PfGW456L13_1896 ignore:reanno::WCS417:GFF4322 ignore:TCDB::Q88P36 PfGW456L13_1897 ABC transporter for D-Galactose and D-Glucose, ATPase component curated:reanno::pseudo13_GW456_L13:PfGW456L13_1897 ignore:reanno::WCS417:GFF4321 ignore:TCDB::Q88P35 galactose-transport: PfGW456L13_1894 PfGW456L13_1895 PfGW456L13_1896 PfGW456L13_1897 # Burkholderia phytofirmans and some other Pseudomonas fluorescens (such as FW300-N2E2) # have a 3-part galactose transporter. It is related to araFGH and also transports L-arabinose. # BPHYT_RS16935 = B2SYR6; Pf6N2E2_5968 = A0A161H4E4 BPHYT_RS16935 galactose ABC transporter, substrate-binding component uniprot:B2SYR6 uniprot:A0A161H4E4 # BPHYT_RS16930 = B2SYR5; Pf6N2E2_5969 = A0A165ZSX8 BPHYT_RS16930 galactose ABC transporter, ATPase component uniprot:B2SYR5 uniprot:A0A165ZSX8 # BPHYT_RS16925 = B2SYR4; Pf6N2E2_5970 = A0A161GM94 BPHYT_RS16925 galactose ABC transporter, permease component uniprot:B2SYR4 uniprot:A0A161GM94 galactose-transport: BPHYT_RS16935 BPHYT_RS16930 BPHYT_RS16925 # PTS systems (forming galactose-6-phosphate) # A close homolog of ptcAB from another strain of Lactococcus lactis is annotated # as being cellobiose-specific ptcA galactose PTS system, EIIA component curated:SwissProt::A2RIE7 ignore:SwissProt::Q9CIE9 ptcB galactose PTS system, EIIB component curated:SwissProt::A2RIE6 ignore:SwissProt::Q9CIF0 ptcEIIC galactose PTS system, EIIC component curated:SwissProt::A2RJV0 galactose-PTS: ptcA ptcB ptcEIIC # Homomeric transporters galP galactose:H+ symporter GalP curated:SwissProt::P0AEP1 curated:CharProtDB::CH_091493 curated:SwissProt::P0AE24 curated:SwissProt::P96710 curated:TCDB::Q9LT15 galactose-transport: galP HP1174 Na+-dependent galactose transporter curated:TCDB::O25788 curated:TCDB::P0C105 galactose-transport: HP1174 gal2 galactose transporter curated:CharProtDB::CH_091029 galactose-transport: gal2 SGLT1 sodium/galactose cotransporter curated:CharProtDB::CH_091086 galactose-transport: SGLT1 CeSWEET1 galactose transporter curated:SwissProt::O45102 galactose-transport: CeSWEET1 # Echvi_1871 (L0FZF3) seems to be a glucose/galactose transporter. # CA265_RS06130 (A0A1X9Z2P8) seems to be a galactose transporter. sglS sodium/galactose cotransporter curated:SwissProt::P96169 uniprot:L0FZF3 uniprot:A0A1X9Z2P8 galactose-transport: sglS MST1 galactose:H+ symporter curated:TCDB::A0ZXK6 galactose-transport: MST1 lacP galactose:H+ symporter curated:TCDB::P07921 galactose-transport: lacP # Ignore TCDB::A1RW34 2.A.1.66.1, which is not characterized # EC:5.3.1.26; only a few characterized members, all heterodimeric lacA galactose-6-phosphate isomerase, lacA subunit curated:SwissProt::P23494 curated:metacyc::MONOMER-2781 lacB galactose-6-phosphate isomerase, lacB subunit curated:SwissProt::P23495 curated:metacyc::MONOMER-2782 lacC D-tagatose-6-phosphate kinase EC:2.7.1.144 lacD D-tagatose-1,6-bisphosphate aldolase (monomeric) curated:BRENDA::Q5HE13 curated:SwissProt::P26593 gatY D-tagatose-1,6-bisphosphate aldolase, catalytic subunit (GatY/KbaY) curated:CharProtDB::CH_024465 curated:SwissProt::P0C8J6 curated:SwissProt::P0C8J7 curated:SwissProt::Q8VS16 curated:SwissProt::Q9KIP8 gatZ D-tagatose-1,6-bisphosphate aldolase, chaperone subunit (GatZ/KbaZ) curated:SwissProt::P0C8J8 curated:SwissProt::P0C8J9 curated:SwissProt::P0C8K0 curated:metacyc::MONOMER-18280 curated:SwissProt::Q8VS12 # Two forms of D-tagatose-1,6-phosphate aldolase are known, homomeric (lacD) or heteromeric (gatYZ or kbaYZ) tag16P-aldolase: lacD tag16P-aldolase: gatY gatZ import fructose.steps:tpi # The tagatose 6-phosphate pathway involves the isomerization of galactose 6-phosphate # to tagatose-6-phosphate (by lacAB), phosphorylation to tagatose 1,6-bisphosphate (by lacC), and an aldolase. galactose-6-phosphate-degradation: lacA lacB lacC tag16P-aldolase tpi # Some curated sequences match an HMM and are annotated as galactokinases, but # without the EC number. galK galactokinase (-1-phosphate forming) EC:2.7.1.6 ignore_other:galactokinase # In the reannotations, galT is often misannotated as 2.7.7.10 (using UTP rather than UDP-glucose # as the substrate) galT UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase EC:2.7.7.12 curated:reanno::Cola:Echvi_0695 curated:reanno::Pedo557:CA265_RS06120 # Echvi_1472 (L0FXG3) is important for galactose utilization and similar to E. coli galE galE UDP-glucose 4-epimerase EC:5.1.3.2 uniprot:L0FXG3 # PH0923 (MONOMER-13382) is both phosphomannomutase and phosphoglucomutase (PMID:16091590) pgmA alpha-phosphoglucomutase EC:5.4.2.2 curated:metacyc::MONOMER-13382 # In the Leloir pathway, galactokinase (galK) forms galactose # 1-phosphate, a uridyltransferase (galT) uses glucose 1-phosphate to # form UDP-galactose, an epimerase (galE) forms UDP-glucose, and this # is converted to glucose 1-phosphate by the same uridyltransferase. # (We initially included the 1-epimerase galM, EC:5.1.3.3, in our model of the # Leloir pathway, but found that in most bacteria, galM proteins were # not important for fitness during growth on galactose; the only # exception was Echvi_0697.) galactose-degradation: galK galT galE pgmA # Some L-arabinose dehydrogenases (EC 1.1.1.46) are bifunctional. # uniprot:Q92RN6 is annotated as a probable galactose dehydrogenase, and mutants are defective in utilization, # but was not given this EC number. galdh D-galactose 1-dehydrogenase (forming 1,4- or 1,5-lactones) EC:1.1.1.48 EC:1.1.1.360 ignore_other:1.1.1.46 curated:SwissProt::Q92RN6 # This step includes both galactono-1,4-lactonases (EC:3.1.1.25) and galactono-1-5-lactonases. # Some galactonolactonases are also L-arabinolactonases (EC 3.1.1.15), so those are ignored. # BRENDA annotates uniprot:A3FJ64 (from Bacillus thuringensis) as this, which seems questionable. # Fitness data confirms diverged lactonases N515DRAFT_1229 (A0A1I2AUG6) and BPHYT_RS16915. # PS417_17365 from P. simiae WCS417 (GFF3393) is a galactono-1,5-lactonase, so is not given the EC number. # Similarly for PfGW456L13_3314. # In Acidovorax sp. GW101-3H11, fitness data suggests that the lactonase is Ac3H11_615 (A0A165IRV8). # And fitness data suggests that SMc00883 (Q92RN9) is a galactonolactonase and an arabinonolaconase # (it has a vague annotation in SwissProt). galactonolactonase galactonolactonase (either 1,4- or 1,5-lactone) EC:3.1.1.25 ignore:BRENDA::A3FJ64 curated:reanno::BFirm:BPHYT_RS16915 uniprot:A0A1I2AUG6 curated:reanno::WCS417:GFF3393 curated:reanno::pseudo13_GW456_L13:PfGW456L13_3314 uniprot:A0A165IRV8 uniprot:Q92RN9 ignore:SwissProt::Q92RN9 ignore_other:3.1.1.15 dgoD D-galactonate dehydratase EC:4.2.1.6 EC:4.2.1.140 # BRENDA misannotates Q9zU29 as dgoK. # Fitness data confirms diverged dgoK proteins BPHYT_RS16950 (B2SYR9), N515DRAFT_1233 (A0A1I2AR49), # and HSERO_RS05160 (D8J0Z3). dgoK 2-dehydro-3-deoxygalactonokinase EC:2.7.1.58 EC:2.7.1.178 ignore:BRENDA::Q9ZU29 uniprot:B2SYR9 uniprot:A0A1I2AR49 uniprot:D8J0Z3 dgoA 2-dehydro-3-deoxy-6-phosphogalactonate aldolase EC:4.1.2.21 EC:4.1.2.55 # The oxidative pathway begins with oxidation to a lactone (by galdh) and hydrolysis to galactonate; # galactonate is then dehydrated, phosphorylated, and cleaved by an aldolase. galactose-degradation: galdh galactonolactonase dgoD dgoK dgoA galactose-utilization: galactose-PTS galactose-6-phosphate-degradation galactose-utilization: galactose-transport galactose-degradation all: galactose-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