ThrH is a magnesium-dependent phosphoserine phosphatase/phosphoserine:homoserine phosphotransferase of Pseudomonas aeruginosa. It can hydrolyze phosphoserine to serine, or transfer its phosphate to homoserine, producing phosphohomoserine and serine. The latter reaction provides an alternative to ThrB in threonine biosynthesis without using ATP as phosphate donor. ThrH overexpression can also complement serB mutants; that result does not establish its indispensability for native serine biosynthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: ThrH coordinates magnesium in its HAD-family phosphoserine-processing active site. Reason: Magnesium is directly supported by the target biochemical/structural study and curated cofactor statement. The ISS source concerns PabB, but this does not negate the independently established target metal-binding claim. Supporting Evidence: file:PSEAE/thrH/thrH-uniprot.txt Name=Mg(2+); |
| GO:0000287 magnesium ion binding | IDA PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | ACCEPT | Summary: ThrH coordinates magnesium in its HAD-family phosphoserine-processing active site. Reason: Magnesium is directly supported by the target biochemical/structural study and curated cofactor statement. The ISS source concerns PabB, but this does not negate the independently established target metal-binding claim. Supporting Evidence: file:PSEAE/thrH/thrH-uniprot.txt Name=Mg(2+); |
| GO:0000287 magnesium ion binding | ISS PMID:2251281 p-Aminobenzoate synthesis in Escherichia coli: purification ... | ACCEPT | Summary: ThrH coordinates magnesium in its HAD-family phosphoserine-processing active site. Reason: Magnesium is directly supported by the target biochemical/structural study and curated cofactor statement. The ISS source concerns PabB, but this does not negate the independently established target metal-binding claim. Supporting Evidence: file:PSEAE/thrH/thrH-uniprot.txt Name=Mg(2+); |
| GO:0004413 homoserine kinase activity | IDA NOT PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | ACCEPT | Summary: Accept the experimentally supported absence of ATP-dependent homoserine kinase activity. Reason: This original annotation is negated: it asserts that ThrH does not have ATP-dependent homoserine kinase activity. PMID:14699121 identifies phosphoserine, rather than ATP, as the phosphoryl donor for homoserine phosphorylation, consistent with the curated UniProt caution against calling ThrH a homoserine kinase. Retain this true negative assertion. The separate positive GO:0043899 phosphoserine:homoserine phosphotransferase annotation is already accepted; replacing this negated term with that activity would incorrectly negate a demonstrated function. Supporting Evidence: PMID:14699121 ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor file:PSEAE/thrH/thrH-uniprot.txt suggesting it is inappropriate to define it as a homoserine kinase |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: ThrH inherits a cytoplasmic localization from the phosphoserine-phosphatase lineage. Reason: The actual PAINT PTN000000002 cytoplasmic assertion is grounded in SerB/PSPH descendants and is assessed SOUND in the committed PTHR43344 review. Human PSPH has independent publication-linked cytosolic localization; ThrH retains the phosphoserine-phosphatase fold and participates in native intracellular amino-acid synthesis. This supports the ancestral localization inference. The target biochemical/crystal experiments are not relabeled as native localization measurements, and the former missing-target-assay rationale alone does not overturn the phylogenetic placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000000002 SUPPORTS TRANSFER Verified cytoplasmic IBD in PTHR43344-paint.tsv and SOUND node assessment. Donor PSPH has publication-linked cytosolic localization; no target-specific relocation is established. Supporting Evidence: file:human/PSPH/PSPH-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:1965857}. |
| GO:0006564 L-serine biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ThrH produces serine during phosphoserine hydrolysis or phosphate transfer to homoserine. Reason: ThrH directly makes serine by phosphoserine hydrolysis or as phosphotransfer coproduct, and overexpression complements serB. Retain conditional serine biosynthetic participation without asserting ThrH is the indispensable native SerB replacement. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase PMID:10220164 thrH overexpression allows complementation of serine auxotrophy of E. coli and P. aeruginosa serB mutants. |
| GO:0006564 L-serine biosynthetic process | TAS PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | KEEP AS NON CORE | Summary: ThrH produces serine during phosphoserine hydrolysis or phosphate transfer to homoserine. Reason: ThrH directly makes serine by phosphoserine hydrolysis or as phosphotransfer coproduct, and overexpression complements serB. Retain conditional serine biosynthetic participation without asserting ThrH is the indispensable native SerB replacement. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase PMID:10220164 thrH overexpression allows complementation of serine auxotrophy of E. coli and P. aeruginosa serB mutants. |
| GO:0009088 L-threonine biosynthetic process | IMP PMID:10220164 ThrH, a homoserine kinase isozyme with in vivo phosphoserine... | ACCEPT | Summary: ThrH supplies phosphohomoserine through an alternative route that complements ThrB loss. Reason: ThrH transfers phosphate from phosphoserine to homoserine, generating phosphohomoserine for threonine synthase. This is actual catalytic participation in L-threonine biosynthetic process. Native P. aeruginosa requires simultaneous thrB and thrH disruption for threonine auxotrophy; the later HPLC chemistry in PMID:14699121 resolves the alternative phosphate donor. Supporting Evidence: PMID:10220164 In P. aeruginosa, threonine auxotrophy is observed only when both thrB and thrH are simultaneously inactivated. PMID:14699121 ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor |
| GO:0016311 dephosphorylation | IDA PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | ACCEPT | Summary: ThrH can hydrolyze the phosphate ester of phosphoserine. Reason: Phosphoserine hydrolysis removes a phosphate group directly. This true process describes the hydrolytic branch, distinct from transfer of that phosphate to homoserine; no supported more specific dephosphorylation term is asserted. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase |
| GO:0036424 L-phosphoserine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ThrH directly hydrolyzes L-phosphoserine to L-serine and phosphate. Reason: Direct phosphoserine hydrolysis assays establish this precise molecular function; catalytic participation is stronger than the complementation-only historical interpretation. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase |
| GO:0036424 L-phosphoserine phosphatase activity | IDA PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | ACCEPT | Summary: ThrH directly hydrolyzes L-phosphoserine to L-serine and phosphate. Reason: Direct phosphoserine hydrolysis assays establish this precise molecular function; catalytic participation is stronger than the complementation-only historical interpretation. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase |
| GO:0036424 L-phosphoserine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ThrH directly hydrolyzes L-phosphoserine to L-serine and phosphate. Reason: Direct phosphoserine hydrolysis assays establish this precise molecular function; catalytic participation is stronger than the complementation-only historical interpretation. Supporting Evidence: PMID:14699121 Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase |
| GO:0043899 phosphoserine:homoserine phosphotransferase activity | IDA PMID:14699121 The thrH gene product of Pseudomonas aeruginosa is a dual ac... | ACCEPT | Summary: ThrH transfers phosphate from phosphoserine to homoserine, producing serine and phosphohomoserine. Reason: PMID:14699121 uses HPLC-based assays to demonstrate transfer of the phosphoserine phosphoryl group to homoserine. Serine is the coproduct and ATP is not the donor. This direct chemistry explains complementation of thrB mutants without calling ThrH an ATP-dependent homoserine kinase; its separate hydrolytic phosphoserine-phosphatase activity is also retained. Supporting Evidence: PMID:14699121 ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor |
| GO:0046654 tetrahydrofolate biosynthetic process | ISS PMID:16605270 Direct detection and kinetic analysis of covalent intermedia... | REMOVE | Summary: tetrahydrofolate biosynthetic process requires rejection of the inferred assignment. Reason: The similarity transfer conflates distinct enzyme families and chemistry: target ThrH is the structurally characterized HAD-like phosphoserine phosphatase/phosphotransferase, whereas these donor papers study chorismate-utilizing aminodeoxychorismate synthase. The experimentally established target fold and reactions contradict a PabB-family assignment; no target chorismate/glutamine catalytic machinery is supported. This is a challenged ISS inference, not removal of an inaccessible target experiment. Supporting Evidence: file:PSEAE/thrH/thrH-uniprot.txt Belongs to the thrH family. PMID:14699121 The structure confirms an overall fold similar to that of PSP. |
| GO:0046820 aminodeoxychorismate synthase activity | ISS PMID:2251281 p-Aminobenzoate synthesis in Escherichia coli: purification ... | REMOVE | Summary: aminodeoxychorismate synthase activity requires rejection of the inferred assignment. Reason: The similarity transfer conflates distinct enzyme families and chemistry: target ThrH is the structurally characterized HAD-like phosphoserine phosphatase/phosphotransferase, whereas these donor papers study chorismate-utilizing aminodeoxychorismate synthase. The experimentally established target fold and reactions contradict a PabB-family assignment; no target chorismate/glutamine catalytic machinery is supported. This is a challenged ISS inference, not removal of an inaccessible target experiment. Supporting Evidence: file:PSEAE/thrH/thrH-uniprot.txt Belongs to the thrH family. PMID:14699121 The structure confirms an overall fold similar to that of PSP. |
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