Definition of myo-inositol catabolism
As rules and steps, or see full text
Rules
Overview: Myo-inositol degradation in GapMind is based on MetaCyc pathways myo-inositol degradation I via inosose dehydratase (link) and pathway II inosose dehydrogenase (link).
- all:
- myo-inositol-transport, iolG, iolE, iolD, iolB, iolC, iolJ, mmsA and tpi
- or myo-inositol-transport, iolG, iolM, iolN, iolO, uxaE, uxuB, uxuA, kdgK and eda
- Comment: Both pathways begin with the 2-dehydrogenase (iolG) forming scyllo-inosose. In pathway I, inosose dehydratase (iolE) forms 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione, followed by a ring-cleaving hydrolase to 5-deoxy-D-glucuronate, isomerization to 5-dehydro-2-deoxy-D-gluconate, phosphorylation, and cleavage by an aldolase to 3-oxopropionate (malonate semialdehyde) and glycerone phosphate; the 3-oxopropionate is oxidized to acetyl-CoA while the glycerone phosphate is converted by triose-phosphate isomerase to glyceraldehyde 3-phosphate. In pathway II, a dehydrogenase forms 3-dehydro scyllo-inosose (also known as 2,4-diketo-inositol), a hydratase forms 5-dehydro-L-gluconate, an epimerase forms D-tagaturonate, another forms to D-fructonate, a reductase forms D-mannonate, a dehydratase forms 2-keto-3-deoxygluconate, a kinase forms 2-keto-3-deoxy-gluconate 6-phosphate, and an aldolase forms glyceraldehyde-3-phosphate and pyruvate.
- myo-inositol-transport:
Steps
PGA1_c07300: myo-inositol ABC transport, substrate-binding component
PGA1_c07310: myo-inositol ABC transporter, permease component
PGA1_c07320: myo-inositol ABC transporter, ATPase component
iatP: myo-inositol ABC transporter, permease component IatP
- Curated sequence B8H230: Inositol ABC transport system, permease protein IatP, component of The myoinositol (high affinity)/ D-ribose (low affinity) transporter IatP/IatA/IbpA. The structure of IbpA with myoinositol bound has been solved
- Total: 1 characterized proteins
iatA: myo-inositol ABC transporter, ATPase component IatA
- Curated sequence B8H229: Inositol transport ATP-binding protein IatA, component of The myoinositol (high affinity)/ D-ribose (low affinity) transporter IatP/IatA/IbpA. The structure of IbpA with myoinositol bound has been solved
- Total: 1 characterized proteins
ibpA: myo-inositol ABC transporter, substrate-binding component IbpA
- Curated sequence B8H228: Inositol ABC transporter, periplasmic inositol-binding protein IbpA, component of The myoinositol (high affinity)/ D-ribose (low affinity) transporter IatP/IatA/IbpA. The structure of IbpA with myoinositol bound has been solved
- Total: 1 characterized proteins
PS417_11885: myo-inositol ABC transporter, substrate-binding component
- Curated sequence GFF2331: Inositol transport system sugar-binding protein
- UniProt sequence A0A0N9WNI6: SubName: Full=Rhizopine-binding protein {ECO:0000313|EMBL:ALI03491.1};
- Comment: The ortholog in P. fluorescens FW300-N2E3 (AO353_21380, A0A0N9WNI6) was not reannotated but does have the phenotype
- Total: 2 characterized proteins
PS417_11890: myo-inositol ABC transporter, ATPase component
PS417_11895: myo-inositol ABC transporter, permease component
iolT: myo-inositol:H+ symporter
- Curated sequence Q8VZR6: Inositol transporter 1. The tonoplast H+:Inositol symporter 1, Int1 (mediates efflux from the tonoplast to the cytoplasm (Schneider et al., 2008) (most similar to 2.A.1.1.63 and 2.A.1.1.62)
- Curated sequence CH_091483: polyol transporter 5. Polyol transporter 5; Protein POLYOL TRANSPORTER 5; AtPLT5; Sugar-proton symporter PLT5. The broad specificity sugar/sugar alcohol (myo-inositol, glycerol, ribose, sorbitol, mannitol, xylitol, erythritol, etc) H+ symporter, AtPLT5 (transports a wide range of hexoses, pentoses, tetroses, sugar alcohols and a sugar acid, but not disaccharides) (Reinders et al., 2005) (expressed in roots, leaves and floral organs)
- Curated sequence CH_091623: Myo-inositol transporter 1. Myo-inositol transporter 1. Myoinositol:H+ symporter
- Curated sequence CH_123508: myo-inositol transporter 2
- Curated sequence O34718: Major myo-inositol transporter IolT. Major myoinositol:H+ symporter, IolT
- Curated sequence P30606: Myo-inositol transporter 2. Myo-inositol transporter 2
- Curated sequence P87110: Myo-inositol transporter 2. MFS myo-inositol transporter
- Curated sequence Q10286: Myo-inositol transporter 1. myo-inositol transporter Itr1
- Curated sequence A8DCT2: Myo inositol uptake porter of 574 aas and 12 TMSs, Fst1
- Curated sequence AIU34725.1: Myo-inositol-specific uptake transporter, ITR1 of 509 aas and 12 TMSs
- Curated sequence Q01440: Myoinositol:H+ symporter, MIT
- Curated sequence Q8NTX0: Myo-Inositol uptake porter, IolT1 (Km=0.2mM)
- Curated sequence E1WAV3: Major myo-inositol transporter, IolT1, of 456 aas
- Curated sequence E1WAV4: Minor myo-inositol transporter, IolT2, of 478 aas
- Curated sequence Q8NL90: Myo-Inositol (Km=0.45mM) uptake porter, IolT2 (Krings et al., 2006). Can not transport D-glucose
- Curated sequence CH_123411: potential myo-inositol transporter
- Curated sequence CH_124311: major myo-inositol transporter iolT
- Comment: Distantly related transporters with the same domain content were grouped together into iolT
- Total: 17 characterized proteins
SMIT1: myo-inositol:Na+ symporter
- Curated sequence Q28728: Sodium/myo-inositol cotransporter 2; Na(+)/myo-inositol cotransporter 2; Sodium-dependent glucose cotransporter; Sodium/glucose cotransporter KST1; rKST1; Sodium/myo-inositol transporter 2; SMIT2; Solute carrier family 5 member 11
- Curated sequence Q8K0E3: Sodium/myo-inositol cotransporter 2; Na(+)/myo-inositol cotransporter 2; Sodium-dependent glucose cotransporter; Sodium/glucose cotransporter KST1; Sodium/myo-inositol transporter 2; SMIT2; Solute carrier family 5 member 11
- Curated sequence Q8WWX8: Sodium/myo-inositol cotransporter 2; Na(+)/myo-inositol cotransporter 2; Sodium-dependent glucose cotransporter; Sodium/glucose cotransporter KST1; Sodium/myo-inositol transporter 2; SMIT2; Solute carrier family 5 member 11. Myoinositol:Na+ symporter, SMIT2 (also transports D-chiro-inositol, D-glucose and D-xylose)
- Curated sequence Q9JKZ2: Sodium/myo-inositol cotransporter; Na(+)/myo-inositol cotransporter; Sodium/myo-inositol transporter 1; SMIT1; Solute carrier family 5 member 3
- Curated sequence Q9Z1F2: Sodium/myo-inositol cotransporter 2; Na(+)/myo-inositol cotransporter 2; Sodium-dependent glucose cotransporter; Sodium/glucose cotransporter KST1; rkST1; Sodium/myo-inositol transporter 2; SMIT2; Solute carrier family 5 member 11
- Curated sequence P31637: Myoinositol:Na+ symporter, SMIT1
- Curated sequence P53794: Sodium/myo-inositol cotransporter (Na(+)/myo-inositol cotransporter) (Sodium/myo-inositol transporter 1) (SMIT1) (Solute carrier family 5 member 3)
- Total: 7 characterized proteins
HMIT: myo-inositol:H+ symporter
- Curated sequence CH_091598: inositol transporter 4. Inositol transporter 4; Myo-inositol-proton symporter INT4; Protein INOSITOL TRANSPORTER 4. High affinity (0.24mM) plasma membrane myoinositol-specific H+ symporter, INT4
- Curated sequence Q921A2: Proton myo-inositol cotransporter; H(+)-myo-inositol cotransporter; Hmit; H(+)-myo-inositol symporter; Solute carrier family 2 member 13
- Curated sequence Q96QE2: Proton myo-inositol cotransporter; H(+)-myo-inositol cotransporter; Hmit; H(+)-myo-inositol symporter; Solute carrier family 2 member 13. Myoinositol:H+ symporter, HMIT (also transport other inositols including scyllo-, muco- and chiro-, but not allo-inositol) (Aouameur et al., 2007). Expressed in the Golgi of the hippocampus and cortex. May also transport inositoltriphosphate (Di Daniel et al., 2009). Interacts directly with γ-secretase (9.B.47.1.1) to regulate its activity and the production of Abeta production, important in Alzheimer's disease
- Curated sequence Q9C757: Probable inositol transporter 2. Low affinity inositol (myoinsoitol (Km = 1 mM), scylloinositol, d-chiroinositol and mucoinositol):H+ symporter (expressed in the anther tapetum, the vasculature, and the leaf mesophyll
- Curated sequence Q9ZQP6: Probable inositol transporter 3
- Total: 5 characterized proteins
iolF: myo-inositol:H+ symporter
kdgK: 2-keto-3-deoxygluconate kinase
- Curated proteins or TIGRFams with EC 2.7.1.45
- Curated proteins or TIGRFams with EC 2.7.1.178
- Ignore hits to Q9ZU29 when looking for 'other' hits (2-dehydro-3-deoxyglucono/galactono-kinase (EC 2.7.1.178))
- Ignore hits to DEHYDDEOXGALACTKIN-MONOMER when looking for 'other' hits (2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178; EC 2.7.1.58). 2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178))
- Comment: The entry for Q9ZU29 is erroneous (the correct accession is Q97U29). EcoCyc 2-dehydro-3-deoxygalactonokinase (dgoK) is given this EC number as well but I could not determine why. It doesn't link to the ketodeoxygluconate kinase reaction.
- Total: 14 characterized proteins
eda: 2-keto-3-deoxygluconate 6-phosphate aldolase
tpi: triose-phosphate isomerase
- Curated proteins or TIGRFams with EC 5.3.1.1
- Ignore hits to P85814 when looking for 'other' hits (Triosephosphate isomerase; TIM; Triose-phosphate isomerase; Allergen Pla o 4; EC 5.3.1.1)
- Comment: Ignore a fragmentary (allergen) sequence
- Total: 1 HMMs and 55 characterized proteins
iolG: myo-inositol 2-dehydrogenase
iolE: scyllo-inosose 2-dehydratase
iolD: 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase
- Curated proteins or TIGRFams with EC 3.7.1.22
- Ignore hits to items matching epi-inositol hydrolase when looking for 'other' hits
- Comment: Erroneous annotations of epi-inositol hydrolases from SEED were "confirmed" by the fitness data and included in reannotations; these are all ignored.
- Total: 2 characterized proteins
iolB: 5-deoxy-D-glucuronate isomerase
iolC: 5-dehydro-2-deoxy-D-gluconate kinase
iolJ: 5-dehydro-2-deoxyphosphogluconate aldolase
- Curated proteins or TIGRFams with EC 4.1.2.29
- Comment: DUF2090 appears to be a substitute for the aldolase. It is distantly related to aldolases and is found fused to iolC in inositol degradation clusters that lack any apparent iolJ. Fitness data confirms that these fusion proteins are required for myo-inositol utilization (but does not prove that the DUF2090 domain is required). These proteins are included in iolJ via their reannotations.
- Total: 11 characterized proteins
mmsA: malonate-semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.18
- Ignore hits to items matching 1.2.1.27 when looking for 'other' hits
- Ignore hits to Q9I702 when looking for 'other' hits (Putative 3-oxopropanoate dehydrogenase; EC 1.2.1.-)
- Comment: Related to methylmalonate-semialdehyde dehydrogenase (1.2.1.27), and many enzymes may have both activities. Q9I702 is annotated as doing this but as "putative" and without the EC number
- Total: 11 characterized proteins
iolM: 2-inosose 4-dehydrogenase
iolN: 2,4-diketo-inositol hydratase
- Curated sequence Q9WYP4: 3-dehydro-scyllo-inosose hydrolase; Diketo-inositol hydrolase; EC 3.7.1.-. 2,4-didehydro-inositol hydratase
- Total: 1 characterized proteins
iolO: 5-dehydro-L-gluconate epimerase
- Curated sequence Q9WYP7: 5-keto-L-gluconate epimerase; Bifunctional nonphosphorylated sugar isomerase; D-erythrose/D-threose isomerase; L-ribulose 3-epimerase; R3E; Nonphosphorylated sugar 3-epimerase; Nonphosphorylated sugar aldose-ketose isomerase; EC 5.1.3.-; EC 5.3.1.-. 5-dehydro-L-gluconate epimerase
- Total: 1 characterized proteins
uxaE: D-tagaturonate epimerase
uxuB: D-mannonate dehydrogenase
uxuA: D-mannonate dehydratase
- Curated proteins or TIGRFams with EC 4.2.1.8
- Ignore hits to A4WA78 when looking for 'other' hits (D-galactonate dehydratase family member Ent638_1932; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to A5KUH4 when looking for 'other' hits (D-galactonate dehydratase family member VSWAT3_13707)
- Ignore hits to A6AMN2 when looking for 'other' hits (D-galactonate dehydratase family member A1Q3065)
- Ignore hits to A6M2W4 when looking for 'other' hits (D-galactonate dehydratase family member Cbei_4837)
- Ignore hits to A6VRA1 when looking for 'other' hits (D-galactonate dehydratase family member Mmwyl1_0037; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to A8RQK7 when looking for 'other' hits (D-galactonate dehydratase family member CLOBOL_02770)
- Ignore hits to B1ELW6 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B3PDB1 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B5GCP6 when looking for 'other' hits (D-galactonate dehydratase family member SSBG_02010)
- Ignore hits to B5QBD4 when looking for 'other' hits (D-galactonate dehydratase family member SeV_A0456; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to B5R541 when looking for 'other' hits (D-galactonate dehydratase family member SEN1436; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to B5RAG0 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B8HCK2 when looking for 'other' hits (D-galactonate dehydratase family member Achl_0790)
- Ignore hits to C6CBG9 when looking for 'other' hits (D-galactonate dehydratase family member Dd703_0947; D-gluconate dehydratase; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to C6CVY9 when looking for 'other' hits (D-galactonate dehydratase family member Pjdr2_1176)
- Ignore hits to C6D9S0 when looking for 'other' hits (D-galactonate dehydratase family member PC1_0802; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to C6DI84 when looking for 'other' hits (D-galactonate dehydratase family member PC1_4063)
- Ignore hits to C7PW26 when looking for 'other' hits (D-galactonate dehydratase family member Caci_4410)
- Ignore hits to C8ZZN2 when looking for 'other' hits (D-galactonate dehydratase family member EGBG_01401)
- Ignore hits to C9A1P5 when looking for 'other' hits (D-galactonate dehydratase family member EGBG_02030)
- Ignore hits to C9CN91 when looking for 'other' hits (D-galactonate dehydratase family member ECAG_02205)
- Ignore hits to C9NUM5 when looking for 'other' hits (D-galactonate dehydratase family member VIC002985)
- Ignore hits to C9Y5D5 when looking for 'other' hits (D-galactonate dehydratase family member Ctu_1p00430)
- Ignore hits to D0KC90 when looking for 'other' hits (D-galactonate dehydratase family member Pecwa_4254)
- Ignore hits to D0X4R4 when looking for 'other' hits (D-galactonate dehydratase family member VME_00770)
- Ignore hits to D4GJ14 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-gluconate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to D7BPX0 when looking for 'other' hits (D-galactonate dehydratase family member SBI_01856; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to D8ADB5 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to D9UNB2 when looking for 'other' hits (D-galactonate dehydratase family member SSLG_02014; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to E1V4Y0 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-gluconate dehydratase; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to Q1QT89 when looking for 'other' hits (D-galactonate dehydratase family member ManD; D-gluconate dehydratase; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to Q2CIN0 when looking for 'other' hits (D-galactonate dehydratase family member OG2516_05608)
- Ignore hits to Q6DAR4 when looking for 'other' hits (D-galactonate dehydratase family member ECA0189)
- Ignore hits to Q8FHC7 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Comment: Many proteins are annotated in SwissProt as "D-galactonate dehydratase family member" but have little activity on D-mannonoate; it is probably not the physiological substrate
- Total: 1 HMMs and 12 characterized proteins
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About GapMind
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:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
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:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
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 paper from 2022 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