As text, or see rules and steps
# Valine degradation in GapMind is based on # MetaCyc pathway L-valine degradation I (metacyc:VALDEG-PWY). # The other pathways do not produce any fixed carbon and are not included. # ABC transporters with 5 components: E. coli livFGHMJ and related systems # (but the alternate substrate-binding protein livK does not transport valine). # Related systems include # livJFGHM from Streptococcus pneumoniae, # braCDEFG from Pseudomonas aeruginosa (braC is the SBP), # and braCDEFG or braC3/braDEFG from R. leguminosarum. # In R. leguminosarum, the proximal braC (Q9L3M3) transports leucine (PMC135202), and likely valine as well. # braC3 (RL3540; Q1MDE9) is a secondary SBP that transports leucine/isoleucine/valine/alanine (PMID:19597156). # LivH/BraD = RL3750/Q1MCU0; LivM/BraE = RL3749/Q1MCU1; # LivG/BraF = RL3748/Q1MCU2; LivF/BraG = RL3747/Q1MCU3. # (The related liv system from Acidovorax, Ac3H11_1692:1695 and Ac3H11_2396, # has not been shown to transport valine.) livF L-valine ABC transporter, ATPase component 1 (LivF/BraG) curated:CharProtDB::CH_003736 curated:TCDB::P21630 curated:TCDB::Q8DQH7 uniprot:Q1MCU3 livG L-valine ABC transporter, ATPase component 2 (LivG/BraF) curated:TCDB::P0A9S7 curated:TCDB::P21629 curated:TCDB::Q8DQH8 uniprot:Q1MCU2 livJ L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3) curated:SwissProt::P21175 curated:TCDB::P0AD96 curated:TCDB::Q8DQI1 uniprot:Q1MDE9 curated:TCDB::Q9L3M3 livH L-valine ABC transporter, permease component 1 (LivH/BraD) curated:TCDB::P21627 curated:TCDB::Q8DQI0 curated:ecocyc::LIVH-MONOMER uniprot:Q1MCU0 # LivM from Streptococcus pneumoniae lacks an N-terminal domain of unknown # function (DUF3382) that is found in E.coli and P. aeruginosa livM L-valine ABC transporter, permease component 2 (LivM/BraE) curated:SwissProt::P22729 curated:TCDB::P21628 curated:TCDB::Q8DQH9 uniprot:Q1MCU1 # Transporters were identified using # query: transporter:valine:L-valine:val valine-transport: livF livG livJ livH livM # Synechocystis sp. NatABCDE TC 3.A.1.4.2) and a similar system from # Anabaena (also known as N-I; TC 3.A.1.4.6) are reported to transport # many amino acids. There isn't any data for valine transport in # Synechocystis, but N-I from Anabaena is thought to contribute to the # reuptake of valine that leaks from the cell (PMC4500139). natA L-valine ABC transporter, ATPase component 1 (NatA) ignore:TCDB::Q55164 curated:TCDB::Q7A2H0 natB L-valine ABC transporter, substrate-binding component NatB ignore:TCDB::Q55387 curated:TCDB::Q8YVY4 natC L-valine ABC transporter, permease component 1 (NatC) ignore:TCDB::P74455 curated:TCDB::Q8YY08 natD L-valine ABC transporter, permease component 2 (NatD) ignore:TCDB::P74318 curated:TCDB::Q8YXD0 natE L-valine ABC transporter, ATPase component 2 (NatE) ignore:TCDB::P73650 curated:TCDB::Q8YT15 valine-transport: natA natB natC natD natE Bap2 L-valine permease Bap2 curated:CharProtDB::CH_091448 curated:CharProtDB::CH_091631 curated:SwissProt::P38084 curated:SwissProt::P41815 curated:TCDB::Q2VQZ4 valine-transport: Bap2 # E. coli BrnQ is reported to use Na+, while P. aeruginosa BraZ is reported to use H+ brnQ L-valine:cation symporter BrnQ/BraZ/BraB curated:TCDB::P0AD99 curated:TCDB::P25185 curated:TCDB::P19072 valine-transport: brnQ phtJ L-valine uptake permease PhtJ curated:TCDB::Q5ZUB4 valine-transport: phtJ bcaP L-valine uptake transporter BcaP/CitA curated:TCDB::S6EX81 valine-transport: bcaP # Non-specific large neutral amino acid tranpsorters from mammals were ignored # Amino acid efflux pumps were ignored # propionyl-CoA is an intermediate in valine degradation import propionate.steps:propionyl-CoA-degradation # 3-methyl-2-oxobutanoate dehydrogenase is one of the activities of # branched-chain alpha-ketoacid dehydrogenases, which pass electrons # to NAD (EC:1.2.1.25) or ferredoxin (EC:1.2.7.7) import leucine.steps:BKD # EC:1.3.8.5 includes isobutyryl-CoA dehydrogenases and sometimes # (2S)-2-methylbutanoyl-CoA dehydrogenases (involved in isoleucine # degradation, usually given EC:1.3.8.5 as well) or # 3-methylbutanoyl-CoA dehydrogenases (involved in leucine # degradation, usually given EC:1.3.8.4). Some enzymes act on all # three methylacyl-CoA substrates. Other genes are required # only for isoleucine degradation and their activity on # isobutyryl-CoA is uncertain, so they are marked ignore. # Also add Psest_2440 (GFF2392), given a different EC number, # and ignore PfGW456L13_2983 (given a different EC but # involved in isoleucine degradation) and # PP_2216 (MONOMER-17424), also involved in isoleucine # degradation. acdH isobutyryl-CoA dehydrogenase EC:1.3.8.5 ignore:reanno::MR1:200844 ignore:reanno::WCS417:GFF2715 ignore:reanno::acidovorax_3H11:Ac3H11_2996 ignore:reanno::psRCH2:GFF2397 ignore:reanno::pseudo1_N1B4:Pf1N1B4_4787 ignore:reanno::pseudo5_N2C3_1:AO356_26355 ignore:reanno::pseudo6_N2E2:Pf6N2E2_1146 ignore:reanno::pseudo13_GW456_L13:PfGW456L13_2983 curated:reanno::psRCH2:GFF2392 ignore:metacyc::MONOMER-17424 import phenylacetate.steps:ech # (S)-3-hydroxybutanoyl-CoA hydro-lyase bch 3-hydroxyisobutyryl-CoA hydrolase EC:3.1.2.4 ignore:BRENDA::Q9SE41 ignore:metacyc::MONOMER-11695 # D5MU22 is probably mmsB but is misannotated in BRENDA mmsB 3-hydroxyisobutyrate dehydrogenase EC:1.1.1.31 ignore:BRENDA::D5MU22 mmsA methylmalonate-semialdehyde dehydrogenase EC:1.2.1.27 # An aminotransferase (not represented) forms 3-methyl-2-oxobutanoate, # the decarboxylating alpha-ketoacid dehydrogenase (BKD) forms isobutanoyl-CoA, # dehydrogenase acdH forms methylacrylyl-CoA (2-methylprop-2-enoyl-CoA), the hydratase # ech forms (S)-3-hydroxy-isobutaonoyl-CoA, a hydrolase forms # (S)-3-hydroxy-isobutanoate, a dehydrogenase forms (S)-methylmalonate # semialdehyde (2-methyl-3-oxopropanoate), and a decarboxylating # dehydrogenase forms propionyl-CoA. all: valine-transport BKD acdH ech bch mmsB mmsA propionyl-CoA-degradation
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