Definition of L-tyrosine catabolism
As rules and steps, or see full text
Rules
Overview: Tyrosine utilization in GapMind is based on MetaCyc pathway tyrosine degradation I, via homogentisate (link). This pathway requires oxygen. Another pathway via 4-hydroxyphenylacetate is known (link), but the 4-hydroxyphenylpyruvate oxidase has not been linked to sequence. The other MetaCyc pathways do not yield fixed carbon or are not reported in prokaryotes.
- all: tyrosine-transport and tyrosine-degradation
- tyrosine-degradation: HPD, hmgA, maiA, fahA and acetoacetate-degradation
- Comment: In pathway I, an aminotransferase (not represented) forms 3-(4-hydroxyphenyl)pyruvate, dioxygenase HPD forms homogentisate, another oxygenase forms 4-maleyl-acetoacetate, an isomerase forms 4-fumaryl-acetoacetate, and a hydrolase yields acetoacetate and fumarate. (Fumarate is part of the TCA cycle so its catabolism is not described.)
- acetoacetate-degradation: acetoacetate-activation and atoB
- Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
- acetoacetate-activation:
- atoA and atoD
- or aacS
- Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
- tyrosine-transport:
Steps
aroP: L-tyrosine transporter (AroP/FywP)
- Curated sequence F2HN33: Transporter for phenylalainine, tyrosine and tryptophan of 449 aas and 12 TMSs, FywP or YsjA
- Curated sequence P15993: Aromatic amino acid:H+ symporter, AroP of 457 aas and 12 TMSs (Cosgriff and Pittard 1997). Transports phenylalanine, tyrosine and tryptophan. aromatic amino acid:H+ symporter AroP. aromatic amino acid:H+ symporter AroP
- Curated sequence Q46065: Aromatic amino acid permease, AroP
- Curated sequence AO356_18530: L-tyrosine transporter
- Curated sequence A2RMP5: Aromatic amino acid permease FywP
- Total: 5 characterized proteins
Ac3H11_2396: L-tyrosine ABC transporter, substrate-binding component component
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Comment: A 5-part ABC transporter for tyrosine and other amino acids was identified in Acidovorax sp. GW101-3H11. It is related to branched-amino-acid transporters. The substrate-binding component (Ac3H11_2396) is not nearby but is cofit.
- Total: 1 characterized proteins
Ac3H11_1695: L-tyrosine ABC transporter, permease component 1
Ac3H11_1694: L-tyrosine ABC transporter, permease component 2
Ac3H11_1693: L-tyrosine ABC transporter, ATPase component 1
Ac3H11_1692: L-tyrosine ABC transporter, ATPase component 2
tyrP: Tyrosine permease
TAT1: L-tyrosine permease TAT1
- Curated sequence CH_091631: valine/tyrosine/tryptophan amino-acid permease. Valine/tyrosine/tryptophan amino-acid permease 1; Tyrosine and tryptophan amino acid transporter 1. Val/Tyr/Trp permease
- Total: 1 characterized proteins
MCT10: L-tyrosine transporter MCT10
- Curated sequence Q91Y77: Monocarboxylate transporter 10; MCT 10; Aromatic amino acid transporter 1; Solute carrier family 16 member 10; T-type amino acid transporter 1. The low affinity aromatic amino acid (Tyr, Trp, Phe) transporter, TAT1 (T-type amino acid transporter), MCT10, Slc16a10
- Total: 1 characterized proteins
CAT: L-tyrosine transporter CAT
tyt1: L-tyrosine:Na+ symporter Tyt1
atoA: acetoacetyl-CoA transferase, A subunit
- Curated sequence ATOD-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &alpha. ; acetyl-CoA:acetoacetyl-CoA transferase subunit α
- Curated sequence HP0691-MONOMER: Succinyl-CoA:3-ketoacid coenzyme A transferase subunit A; Succinyl-CoA:3-oxoacid CoA-transferase; OXCT A; EC 2.8.3.5. succinyl-CoA:acetoacetate CoA-transferase subunit A (EC 2.8.3.5)
- Curated sequence GFF1045: acetyl-CoA:acetoacetate CoA transferase, A subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2111: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit A
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
atoD: acetoacetyl-CoA transferase, B subunit
- Curated sequence ATOA-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &beta. ; acetyl-CoA:acetoacetyl-CoA transferase subunit β
- Curated sequence HP0692-MONOMER: succinyl-CoA:acetoacetate CoA-transferase subunit B (EC 2.8.3.5)
- Curated sequence GFF1044: acetyl-CoA:acetoacetate CoA transferase, B subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2112: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit B
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
aacS: acetoacetyl-CoA synthetase
atoB: acetyl-CoA C-acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.9
- Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
- Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
- Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
- Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
- Total: 36 characterized proteins
HPD: 4-hydroxyphenylpyruvate dioxygenase
- Curated proteins or TIGRFams with EC 1.13.11.27
- Ignore hits to Q8EKK9 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Ignore hits to Q9RSJ4 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Comment: Q8EKK9 and Q9RSJ4 are misannotated in BRENDA
- Total: 1 HMMs and 17 characterized proteins
hmgA: homogentisate dioxygenase
maiA: maleylacetoacetate isomerase
fahA: fumarylacetoacetate hydrolase
Links
Downloads
Related tools
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:
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