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 the paper from 2019 on GapMind for amino acid biosynthesis, the preprint on GapMind for carbon sources, or view the source code.
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