hom (PA3736) encodes homoserine dehydrogenase (HDH, EC 1.1.1.3) of Pseudomonas aeruginosa. The enzyme reduces L-aspartate 4-semialdehyde to L-homoserine with NADH or NADPH, the third step from aspartate and the branch point that supplies homoserine to both threonine biosynthesis (via homoserine kinase and threonine synthase) and methionine biosynthesis (via homoserine O-succinyltransferase MetXS). It has an N-terminal NAD(P)-binding domain, a central catalytic domain and a C-terminal ACT domain, and its activity is feedback-inhibited by threonine. hom lies at the thr locus, apparently co-transcribed with thrC (threonine synthase), and is expressed constitutively. It is the only homoserine dehydrogenase encoded in the PAO1 genome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | MODIFY | Summary: Rhea2GO mapping of the NAD+-dependent homoserine dehydrogenase reaction (RHEA:15757) to the generic EC 1.1.1.1 alcohol dehydrogenase (NAD+) term. Reason: Homoserine is formally an alcohol and aspartate semialdehyde an aldehyde, so the reaction fits the generic definition, but the term names a different enzyme class (EC 1.1.1.1) and adds nothing. The NAD+ reaction is part of the EC 1.1.1.3 homoserine dehydrogenase activity already carried by the gene; replace with GO:0004412. Proposed replacements: homoserine dehydrogenase activity Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt Reaction=L-homoserine + NAD(+) = L-aspartate 4-semialdehyde + NADH + H(+); Xref=Rhea:RHEA:15757 |
| GO:0004412 homoserine dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000752178 (PTHR43331 homoserine dehydrogenase), seeded by this gene and B. subtilis Hom (P19582). The target in its own WITH/FROM is expected. Reason: All 41 leaves of the node are homoserine dehydrogenases, and the second seed supports the IBD independently of the PseudoCAP row. P29365 has the full HDH architecture and family signature and is the only HDH in PAO1; HDH activity of the P. aeruginosa enzyme was reported when the gene was cloned. Supporting Evidence: PMID:1333566 HDH activity was feedback inhibited by threonine file:PSEAE/hom/hom-uniprot.txt Belongs to the homoserine dehydrogenase family. |
| GO:0004412 homoserine dehydrogenase activity | IDA PMID:10220164 ThrH, a homoserine kinase isozyme with in vivo phosphoserine... | ACCEPT | Summary: PseudoCAP row citing Patte et al. 1999, a paper on the ThrH homoserine kinase isozyme. One of two seeds of the PTN000752178 HDH IBD. Reason: The activity is correct for this gene: the 1992 paper from the same group that cloned hom reports HDH activity and its threonine feedback inhibition. The cited 1999 abstract is about ThrB and ThrH and does not mention hom or HDH; PseudoCAP attached the same paper to thrB, hom and thrH, which looks like a batch citation. The full text is not available to check, so I keep the row (deferring to the curator) and flag the reference for checking rather than removing it. Supporting Evidence: PMID:1333566 HDH activity was feedback inhibited by threonine |
| GO:0004412 homoserine dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro HDH family IPR016204, EC 1.1.1.3, Rhea) for HDH activity. Reason: Same correct claim as the IBA and IDA rows; the family signature supports it. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt Belongs to the homoserine dehydrogenase family. |
| GO:0004412 homoserine dehydrogenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt ISS from the structurally characterised homoserine dehydrogenase P31116. Reason: Same correct claim; the curated UniProt function and reactions are transferred from P31116. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt the third step in the biosynthesis of threonine and methionine from aspartate |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the HDH catalytic domain and family signatures. Reason: Correct but very general. The step Hom catalyses is L-homoserine biosynthesis (GO:0009090), the precursor of both threonine and methionine; the gene already carries the two downstream biosynthetic processes. Proposed replacements: L-homoserine biosynthetic process Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt pathway; L-homoserine from L-aspartate: step 3/3. |
| GO:0009088 L-threonine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000752178, whose L-threonine biosynthesis IBD rests solely on this gene's PseudoCAP IDA row (41 leaf IBAs). Reason: Hom catalyses step 3 of the 5-step threonine pathway from aspartate, so the enzyme does part of the work of the process. Every leaf under the node is an HDH, so the term suits the clade. The node term is incomplete rather than wrong: HDH equally feeds methionine biosynthesis. Although the seed's cited reference is questionable, the claim is independently supported. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt L-threonine biosynthesis; L-threonine from L-aspartate: step 3/5. PMID:1333566 Three genes from Pseudomonas aeruginosa involved in threonine biosynthesis, hom, thrB and thrC, encoding homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase (TS), respectively, have been cloned and sequenced. |
| GO:0009088 L-threonine biosynthetic process | IDA PMID:10220164 ThrH, a homoserine kinase isozyme with in vivo phosphoserine... | ACCEPT | Summary: PseudoCAP row citing Patte et al. 1999 (ThrH paper); sole seed of the PTN000752178 L-threonine biosynthesis IBD. Reason: The process claim is correct for Hom (see the IBA row), so the row stands. The cited reference is questionable for this gene and is flagged for checking on the MF IDA row; the same defect applies here. Supporting Evidence: PMID:1333566 Three genes from Pseudomonas aeruginosa involved in threonine biosynthesis, hom, thrB and thrC, encoding homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase (TS), respectively, have been cloned and sequenced. |
| GO:0009088 L-threonine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (L-threonine biosynthesis) to the threonine biosynthetic process. Reason: Same correct claim as the IBA row. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt L-threonine biosynthesis; L-threonine from L-aspartate: step 3/5. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the aspartate/homoserine dehydrogenase NAD-binding domain. Reason: True but general; the specific activity, homoserine dehydrogenase activity (GO:0004412), is a descendant already carried by the gene. Proposed replacements: homoserine dehydrogenase activity Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt Belongs to the homoserine dehydrogenase family. |
| GO:0050661 NADP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO from the NAD(P)-binding domain. Reason: Hom uses NADPH or NADH as cosubstrate, so binding NADP is true; it is part of the dehydrogenase activity rather than a separate function. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt Reaction=L-homoserine + NADP(+) = L-aspartate 4-semialdehyde + NADPH + H(+) |
| GO:0070403 NAD+ binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS from P31116 NAD+-binding residues. Reason: True (the enzyme uses NAD(H) as well as NADP(H)), but cofactor binding is part of the dehydrogenase activity, not a separate function. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt Reaction=L-homoserine + NAD(+) = L-aspartate 4-semialdehyde + NADH + H(+) |
| GO:0071265 L-methionine biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt ISS (UniPathway L-methionine biosynthesis via de novo pathway, step 3/3 of homoserine formation). Reason: Homoserine is the precursor of methionine in P. aeruginosa via the MetXS homoserine O-succinyltransferase (PA0390) and MetZ O-succinylhomoserine sulfhydrylase (PA3107). Hom is the only homoserine dehydrogenase in PAO1, so it supplies this branch as well as threonine. Supporting Evidence: file:PSEAE/hom/hom-uniprot.txt the third step in the biosynthesis of threonine and methionine from aspartate |
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Download this section (compressed HTML)Q: Does the full text of PMID:10220164 (Patte et al. 1999, ThrH) contain a homoserine dehydrogenase assay or hom mutant, or should the PseudoCAP hom IDA rows cite PMID:1333566 instead?
Q: Should PTN000752178 also carry an L-methionine biosynthetic process (or L-homoserine biosynthetic process) IBD, since every homoserine dehydrogenase in the clade supplies homoserine to both branches?
Experiment: Construct a clean hom deletion in PAO1 and test for combined threonine and methionine auxotrophy (with homoserine rescue), and assay purified Hom with NADH versus NADPH and with threonine, to confirm its sole-HDH role and cofactor preference.
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