THI12 (YNL332W) encodes a 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase of the NMT1/THI5 family, one of four almost identical subtelomeric paralogues (THI5, THI11, THI12, THI13) that make the pyrimidine half of thiamine. By similarity to THI5, whose sequence differs from it at only a few positions, it is an iron-dependent homodimeric enzyme that builds HMP-P from pyridoxal 5'-phosphate and the side chain of one of its own histidine residues in a single turnover. The four paralogues are functionally redundant for aerobic HMP synthesis from the vitamin B6 pathway, and the family is induced by thiamine limitation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | MODIFY | Summary: Root MF with ND is outdated: THI12 is a near-identical paralogue of THI5, whose HMP-P synthase activity was demonstrated (PMID:23048037), and THI12 already carries the ISS annotation to GO:0106344. Reason: Molecular function can now be assigned by sequence similarity to THI5 and genetic redundancy. NO_DATA re-check: PMID:12777485 shows in S. cerevisiae that THI12 alone supports HMP formation. Proposed replacements: 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP Supporting Evidence: PMID:12777485 functionally redundant in terms of HMP formation for thiamin biosynthesis |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: No experimental localisation exists for THI12; the near-identical paralogues are hard to distinguish by tagging or proteomics. Presumed cytosolic but not shown, so ND remains accurate. Reason: Accurately records the absence of localisation data. Supporting Evidence: PMID:12777485 The THI5 gene family of Saccharomyces cerevisiae comprises four highly conserved members |
| GO:0009228 thiamine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001267680) with S. pombe nmt1, C. albicans THI5 and the four S. cerevisiae paralogues, including THI12, as descendants. Correct. Reason: Core BP. Supporting Evidence: PMID:12777485 functionally redundant in terms of HMP formation for thiamin biosynthesis |
| GO:0009228 thiamine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro (IPR027939, NMT1/THI5 family) mapping to thiamine biosynthesis; correct. Reason: Core BP. Supporting Evidence: PMID:12777485 each promotes synthesis of HMP from the pyridoxine (vitamin B(6)) biosynthetic pathway |
| GO:0009228 thiamine biosynthetic process | IGI PMID:12777485 The THI5 gene family of Saccharomyces cerevisiae: distributi... | ACCEPT | Summary: Combinatorial single-to-quadruple deletion analysis shows THI12 is redundant with THI5 (SGD:S000001836) for HMP formation (PMID:12777485). Reason: Core BP; genetic redundancy evidence. Supporting Evidence: PMID:12777485 all combinations of the single, double, triple and quadruple deletion mutants were constructed |
| GO:0009228 thiamine biosynthetic process | IGI PMID:12777485 The THI5 gene family of Saccharomyces cerevisiae: distributi... | ACCEPT | Summary: Combinatorial single-to-quadruple deletion analysis shows THI12 is redundant with THI13 (SGD:S000002403) for HMP formation (PMID:12777485). Reason: Core BP; genetic redundancy evidence. Supporting Evidence: PMID:12777485 all combinations of the single, double, triple and quadruple deletion mutants were constructed |
| GO:0009228 thiamine biosynthetic process | IGI PMID:12777485 The THI5 gene family of Saccharomyces cerevisiae: distributi... | ACCEPT | Summary: Combinatorial single-to-quadruple deletion analysis shows THI12 is redundant with THI11 (SGD:S000003917) for HMP formation (PMID:12777485). Reason: Core BP; genetic redundancy evidence. Supporting Evidence: PMID:12777485 all combinations of the single, double, triple and quadruple deletion mutants were constructed |
| GO:0009229 thiamine diphosphate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00060 (thiamine diphosphate biosynthesis) mapping. HMP-P is a ThDP precursor, so this is correct; thiamine biosynthesis is the more direct process. Reason: Correct pathway assignment. Supporting Evidence: file:yeast/THI12/THI12-uniprot.txt PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis. |
| GO:0106344 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from THI5 (P43534), whose HMP-P synthase activity was characterised (PMID:23048037). THI12 differs from THI5 at only 1 of 340 residues (ungapped comparison of the UniProt sequences) and is genetically redundant with it, so the transfer is sound. Reason: Core MF; near-identical paralogue with genetic redundancy. Supporting Evidence: PMID:12777485 functionally redundant in terms of HMP formation for thiamin biosynthesis PMID:23048037 the use of pyridoxal 5'-phosphate as a substrate rather than as a cofactor |
Loading supporting content…
Download this section (compressed HTML)Q: Is THI12 expressed and active as a protein under thiamine limitation, or does it contribute mainly as a backup copy? Its residue differences from THI5 have not been tested.
Experiment: Quantify THI12-specific peptides (at the residues that differ from its paralogues) by targeted proteomics under thiamine limitation, and test single-copy strains (other three paralogues deleted) for HMP-P synthesis rate.
Protein involved in synthesis of the thiamine precursor HMP; member of a subtelomeric gene family including THI5, THI11, THI12, and THI13; hydroxymethylpyrimidine is also known as HMP
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)