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The identity supplied by UniProt is internally consistent: Q9Y7T6 corresponds to ORF SPCC63.10c, named sec59, in Schizosaccharomyces pombe strain 972, and is annotated as dolichol kinase Sec59 (EC 2.7.1.108), a member of the polyprenol-kinase family containing the Polypren_kinase domain (InterPro IPR032974). However, exact searches for Q9Y7T6 and SPCC63.10c found no primary publication directly characterizing this S. pombe protein. The gene symbol SEC59 is therefore literature-ambiguous across yeast species: most experimental work concerns the Saccharomyces cerevisiae or Kluyveromyces lactis ortholog, not Q9Y7T6. Those studies are used below only as orthology-based evidence.
The best-supported functional assignment is that S. pombe Sec59 is an integral endoplasmic-reticulum membrane enzyme that catalyzes:
dolichol + CTP → dolichol phosphate (Dol-P) + CDP
Its principal role is to maintain the ER Dol-P pool used as the lipid carrier for N-linked oligosaccharide assembly and, after formation of Dol-P-mannose or Dol-P-glucose, for protein O-mannosylation, later luminal steps of N-glycan assembly, and GPI-anchor biosynthesis. This assignment is strong by family conservation and ortholog biochemistry, but it remains unverified directly for recombinant Q9Y7T6 or S. pombe membranes. (heller1992saccharomycescerevisiaesec59 pages 1-2, ziogiene2024dolicholkinasesfrom pages 1-2)
| Feature | Best-supported annotation | Evidence level | Important limitation |
|---|---|---|---|
| Identity | sec59 / SPCC63.10c / UniProt Q9Y7T6 from Schizosaccharomyces pombe strain 972; annotated as dolichol kinase (EC 2.7.1.108). | Curated annotation supplied by UniProt/PomBase | Exact-accession and ORF searches found no primary study directly characterizing the S. pombe protein; SEC59 results from other yeasts must not be treated as direct evidence. |
| Catalytic reaction | Dolichol + CTP → dolichol phosphate (Dol-P) + CDP. This is the terminal phosphorylation step in de novo Dol-P production. | Function inferred for Q9Y7T6 from curated annotation and conserved yeast ortholog biochemistry; direct S. cerevisiae membrane assays used dolichol and [γ-³²P]CTP (heller1992saccharomycescerevisiaesec59 pages 1-2, ziogiene2024dolicholkinasesfrom pages 1-2) | The reaction has not been demonstrated biochemically with purified Q9Y7T6 or S. pombe membranes. |
| Substrate and donor specificity | Hydrophobic free dolichol is the phosphoryl acceptor; CTP, rather than the more usual ATP, is the phosphoryl donor. | Strong ortholog evidence from S. cerevisiae Sec59 assays and conserved dolichol kinases (heller1992saccharomycescerevisiaesec59 pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4) | Chain-length preference and kinetic constants have not been reported for Q9Y7T6; activity toward other polyprenols is therefore unresolved. |
| Localization and topology | Predicted integral endoplasmic-reticulum membrane protein, with the conserved C-terminal catalytic/CTP-binding region facing the cytosol, where early Dol-P-dependent glycan assembly occurs. | Ortholog-based inference: yeast and human dolichol kinases are hydrophobic ER proteins, and conserved topology places the catalytic region cytosolically (heller1992saccharomycescerevisiaesec59 pages 3-4, ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4) | No direct microscopy, fractionation, protease-protection, or topology experiment was found for S. pombe Sec59. Earlier predictions of numerous transmembrane segments remain structurally unverified (ziogiene2024dolicholkinasesfrom pages 2-4). |
| Protein family/domain | Member of the polyprenol kinase family, containing the Polypren_kinase domain (InterPro IPR032974); recent comparative modeling supports functionally cooperating N- and C-terminal regions, with the conserved C-terminal region crucial for catalysis. | UniProt/InterPro annotation supplied for Q9Y7T6 plus 2024 cross-species sequence, AlphaFold3, chimera, and complementation evidence (ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 14-15) | Two-domain architecture is model- and complementation-supported, not an experimentally solved Q9Y7T6 structure; domain behavior in S. pombe is untested. |
| N-linked glycosylation | Sec59-generated Dol-P supplies the ER lipid carrier on which the dolichol-linked oligosaccharide precursor is assembled before transfer to nascent proteins. | Strong conserved-pathway inference; reduced Sec59 activity directly caused Dol-P depletion and N-hypoglycosylation in S. cerevisiae (heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3, ziogiene2024dolicholkinasesfrom pages 1-2) | No Q9Y7T6 perturbation followed by S. pombe glycan analysis was found. |
| O-mannosylation | Dol-P is converted to Dol-P-mannose, the membrane-linked mannose donor used for protein O-mannosylation; Q9Y7T6 is therefore expected to support this pathway indirectly by supplying Dol-P. | Conserved-pathway and ortholog-mutant evidence; S. cerevisiae sec59 deficiency abolished O-mannosylation under restrictive conditions (heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3, ziogiene2024dolicholkinasesfrom pages 1-2) | This is not evidence that Sec59 itself transfers mannose, nor has the dependency been tested directly in S. pombe. |
| GPI-anchor biosynthesis | Dol-P-mannose derived from the Sec59 product supplies mannose for glycosylphosphatidylinositol-anchor assembly. | Conserved-pathway inference supported by loss of GPI-anchor synthesis in severely impaired S. cerevisiae sec59 cells (heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3, ziogiene2024dolicholkinasesfrom pages 1-2) | No direct GPI-anchor phenotype has been reported for Q9Y7T6; Sec59 is upstream of, rather than a structural component of, the GPI-assembly machinery. |
| Expected loss-of-function phenotype | Severe depletion of Dol-P should cause ER hypoglycosylation, accumulation of incompletely glycosylated proteins, impaired secretion, O-mannosylation/GPI-anchor defects, and likely major growth or viability impairment. In S. cerevisiae sec59, Dol-P fell to 48% of wild type permissively and below 10% restrictively; kinase activity was 5% and 3% of wild type, respectively (heller1992saccharomycescerevisiaesec59 pages 3-4, heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3). | Strong biochemical and genetic evidence in the S. cerevisiae ortholog; cross-species complementation supports conservation (ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 9-11) | These are phenotype predictions for S. pombe, not observed Q9Y7T6 phenotypes; tolerance differs among yeasts, as illustrated by milder K. lactis defects (ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4). |
| Recent evidence and application | A 2024 study showed that human and C. elegans dolichol kinases complemented defective kinase function in two yeasts; separately expressed N- and C-terminal regions restored CPY glycosylation, supporting deep functional conservation and modularity. Partial Dol-P limitation in a K. lactis mutant was also associated with approximately threefold higher recombinant α-amylase secretion, suggesting a possible glycoengineering application (ziogiene2024dolicholkinasesfrom pages 14-15, ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4, ziogiene2024dolicholkinasesfrom pages 9-11). | Recent peer-reviewed ortholog and engineering evidence | The 2024 work did not study Q9Y7T6 or S. pombe; complementation demonstrates conserved core function but not identical native regulation, topology, or substrate range. |
| Literature status | Literature is limited for this specific protein. The defensible annotation is a predicted S. pombe dolichol kinase supported by UniProt/PomBase identity, family/domain conservation, and strong biochemical evidence for fungal/eukaryotic orthologs. | Evidence synthesis | Major gaps are direct localization, native substrate profile, kinetics, structure, interaction partners, and loss-of-function analysis in S. pombe. |
Table: Evidence-graded annotation of S. pombe Sec59/Q9Y7T6, separating supplied database annotation from biochemical and genetic findings in other yeast species. The table highlights both the strongly conserved functional model and the absence of direct experimental characterization of Q9Y7T6.
Dolichol kinase phosphorylates the terminal hydroxyl of free membrane-associated dolichol, producing Dol-P. Unusually for a kinase, the phosphoryl donor is CTP rather than ATP. In the definitive S. cerevisiae study, membrane fractions were incubated with pig-liver dolichol and [γ-³²P]CTP; radiolabeled Dol-P was then isolated chromatographically. This directly demonstrated a membrane-associated, CTP-dependent dolichol-kinase reaction for the ortholog. (heller1992saccharomycescerevisiaesec59 pages 1-2)
Specificity for dolichol as acceptor and CTP as donor is therefore well supported at the conserved-family level. Nevertheless, there are no reported Michaelis constants, turnover numbers, preferred dolichol chain lengths, or comparative activities toward polyprenols for Q9Y7T6. It would be premature to claim strict chain-length specificity in S. pombe.
Sec59 catalyzes the terminal phosphorylation step in de novo Dol-P production, downstream of polyisoprenoid synthesis. It does not synthesize the dolichol chain, transfer sugars, or assemble glycans directly. Instead, it supplies the activated membrane lipid on which several ER glycosylation pathways depend. (choy2025exploringsmallmolecules pages 24-28, ziogiene2024dolicholkinasesfrom pages 1-2)
Conserved eukaryotic dolichol kinases are highly hydrophobic, polytopic ER-membrane proteins. Available topology analyses place the conserved C-terminal CTP-binding/catalytic region on the cytoplasmic side of the ER, consistent with initial Dol-P-dependent oligosaccharide assembly occurring on that face. A 2024 analysis noted that earlier predictions proposed as many as 15 membrane-spanning segments, whereas AlphaFold-based models favored two cooperating structural/functional regions; no experimentally determined atomic structure was available. (ziogiene2024dolicholkinasesfrom pages 2-4)
For Q9Y7T6, ER residence and cytosolic catalytic orientation should be regarded as high-confidence orthology-based predictions, not direct localization results. No S. pombe-specific fluorescence microscopy, membrane fractionation, protease-protection experiment, or topology map was found.
Dol-P is the membrane carrier from which dolichol-pyrophosphate-linked oligosaccharides are assembled before transfer to nascent secretory and membrane proteins. Therefore, inadequate Sec59 activity limits lipid-linked oligosaccharide supply and produces underoccupied or truncated N-glycans. In S. cerevisiae sec59 mutants, incompletely glycosylated, inactive proteins accumulated in the ER and secretion of carboxypeptidase Y, invertase, and α-factor was impaired. (ziogiene2024dolicholkinasesfrom pages 1-2)
Dol-P can receive mannose from GDP-mannose to form Dol-P-mannose. This lipid-linked donor supports protein O-mannosylation and supplies mannose during GPI-anchor assembly. In severely impaired S. cerevisiae sec59 cells, O-mannosylation and GPI-anchor synthesis were abolished, demonstrating that the Dol-P supply can become limiting for both pathways. Sec59 itself is not the mannosyltransferase and is not a structural GPI-assembly component; its role is upstream substrate provision. (heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3)
Dol-P also supports formation of Dol-P-glucose, used during luminal completion of the lipid-linked N-glycan precursor. Thus, the predicted biochemical consequence of Q9Y7T6 loss is not confined to one glycosyltransferase reaction but reflects depletion of a shared lipid carrier pool. (ziogiene2024dolicholkinasesfrom pages 1-2)
The strongest classical evidence is Heller, Orlean and Adair, published August 1992 in PNAS (DOI/URL). In S. cerevisiae, Sec59-deficient membranes retained only 5% of wild-type dolichol-kinase activity at 24°C and 3% at 38°C. Absolute activities were 58.9 ± 9.8 and 63.9 ± 19.5 pmol·h⁻¹·mg⁻¹ for wild type, compared with 3.1 ± 0.3 and 1.6 ± 0.1 for the mutant. Multicopy SEC59 increased activity to 843.0 ± 57.2 and 619.2 ± 29.8 pmol·h⁻¹·mg⁻¹—approximately 14.3-fold and 10.5-fold above wild type, respectively. (heller1992saccharomycescerevisiaesec59 pages 3-4)
The mutant retained approximately 48% of wild-type Dol-P at permissive temperature and less than 10% at restrictive temperature. Cis-prenyltransferase and Dol-PP phosphatase activities remained normal. Moreover, supplying exogenous Dol-P restored Dol-P-mannose synthesis, showing that the downstream synthase was functional and that Dol-P availability was the proximate biochemical defect. (heller1992saccharomycescerevisiaesec59 pages 1-2, heller1992saccharomycescerevisiaesec59 pages 2-3)
These data strongly validate the conserved SEC59 functional assignment, but all numerical values above are from S. cerevisiae, not S. pombe.
The most relevant recent paper is Ziogiene et al., published November 2024 in PLOS ONE (DOI/URL). Sequence comparison, AlphaFold3 modeling, domain expression, chimeric proteins, and cross-species complementation supported a two-region functional model. The conserved C-terminal region contains the catalytic dolichol-kinase machinery and is crucial for activity, whereas the less-conserved N-terminal region appears to enhance structure, activity, or regulation. A single C-terminal-domain copy was generally insufficient for normal glycosylation, but overexpression improved function; co-expression of separated N- and C-terminal regions restored carboxypeptidase-Y glycosylation to approximately wild-type levels in yeast assays. (ziogiene2024dolicholkinasesfrom pages 14-15, ziogiene2024dolicholkinasesfrom pages 9-11)
Full-length human and Caenorhabditis elegans dolichol kinases complemented defective DK function in K. lactis and S. cerevisiae. N-terminal regions from K. lactis and C. elegans could also be exchanged to create active chimeras. This provides strong evidence for deep conservation of the catalytic system despite divergent N-terminal sequences. It does not prove that Q9Y7T6 has identical regulation or topology. (ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4)
No 2023–2024 study directly examining Q9Y7T6 or SPCC63.10c was found. Accordingly, the latest research advances refine the family-level structural model rather than the organism-specific annotation.
Dolichol-kinase manipulation is relevant to yeast glycoengineering and recombinant-protein production, because changing the Dol-P supply can alter glycan occupancy, ER quality control, and secretion. In one K. lactis mutant context discussed in the 2024 study, partial dolichol-kinase deficiency was associated with approximately threefold greater recombinant α-amylase secretion than wild type. This suggests that carefully tuned—not complete—Dol-P limitation may sometimes redirect secretory processing. The result is species- and construct-dependent and cannot yet be transferred directly to S. pombe. (ziogiene2024dolicholkinasesfrom pages 2-4)
The pathway also has medical relevance through human DOLK deficiency and congenital disorders of glycosylation, but that does not make S. pombe sec59 a disease gene. Its practical value is primarily as a conserved experimental model for ER lipid-carrier metabolism and as a potential engineering node controlling glycosylation and secretion.
The convergent evidence supports the following expert assessment:
The expected consequence of strong S. pombe sec59 depletion is broad ER hypoglycosylation, secretory-protein retention, defective O-mannosylation/GPI anchoring, cell-wall abnormalities, and severe growth impairment. This remains a testable prediction rather than a reported Q9Y7T6 phenotype; yeast species can differ substantially in their tolerance of partial Dol-P depletion. (ziogiene2024dolicholkinasesfrom pages 1-2, ziogiene2024dolicholkinasesfrom pages 2-4)
The most informative direct tests would be: (1) Q9Y7T6 complementation of a conditional yeast SEC59 mutant; (2) [γ-³²P]CTP or LC–MS-based dolichol-kinase assays using purified protein or S. pombe microsomes; (3) systematic testing of endogenous dolichol chain lengths and polyprenol alternatives; (4) endogenous fluorescent tagging plus membrane fractionation and topology mapping; and (5) conditional depletion followed by Dol-P lipidomics, lipid-linked-oligosaccharide profiling, N-glycoproteomics, O-mannosylation/GPI-anchor assays, and secretion measurements.
Overall, the gene symbol is ambiguous across organisms and literature is limited for this specific protein, but the UniProt assignment is strongly supported by domain/family information and exceptionally coherent ortholog biochemistry. The defensible annotation is therefore: an inferred ER dolichol kinase that uses CTP to generate the Dol-P lipid carrier required for multiple glycosylation pathways, with direct experimental validation in S. pombe still needed.
References
(heller1992saccharomycescerevisiaesec59 pages 1-2): L Heller, P Orlean, and WL Adair Jr. Saccharomyces cerevisiae sec59 cells are deficient in dolichol kinase activity. Proceedings of the National Academy of Sciences of the United States of America, 89 15:7013-6, Aug 1992. URL: https://doi.org/10.1073/pnas.89.15.7013, doi:10.1073/pnas.89.15.7013. This article has 85 citations and is from a highest quality peer-reviewed journal.
(ziogiene2024dolicholkinasesfrom pages 1-2): Danguole Ziogiene, Andrius Burdulis, Albertas Timinskas, Ruta Zinkeviciute, Emilija Vasiliunaite, Milda Norkiene, and Alma Gedvilaite. Dolichol kinases from yeast, nematode and human can replace each other and exchange their domains creating active chimeric enzymes in yeast. PLOS ONE, 19:e0313330, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0313330, doi:10.1371/journal.pone.0313330. This article has 1 citations and is from a peer-reviewed journal.
(ziogiene2024dolicholkinasesfrom pages 2-4): Danguole Ziogiene, Andrius Burdulis, Albertas Timinskas, Ruta Zinkeviciute, Emilija Vasiliunaite, Milda Norkiene, and Alma Gedvilaite. Dolichol kinases from yeast, nematode and human can replace each other and exchange their domains creating active chimeric enzymes in yeast. PLOS ONE, 19:e0313330, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0313330, doi:10.1371/journal.pone.0313330. This article has 1 citations and is from a peer-reviewed journal.
(heller1992saccharomycescerevisiaesec59 pages 3-4): L Heller, P Orlean, and WL Adair Jr. Saccharomyces cerevisiae sec59 cells are deficient in dolichol kinase activity. Proceedings of the National Academy of Sciences of the United States of America, 89 15:7013-6, Aug 1992. URL: https://doi.org/10.1073/pnas.89.15.7013, doi:10.1073/pnas.89.15.7013. This article has 85 citations and is from a highest quality peer-reviewed journal.
(ziogiene2024dolicholkinasesfrom pages 14-15): Danguole Ziogiene, Andrius Burdulis, Albertas Timinskas, Ruta Zinkeviciute, Emilija Vasiliunaite, Milda Norkiene, and Alma Gedvilaite. Dolichol kinases from yeast, nematode and human can replace each other and exchange their domains creating active chimeric enzymes in yeast. PLOS ONE, 19:e0313330, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0313330, doi:10.1371/journal.pone.0313330. This article has 1 citations and is from a peer-reviewed journal.
(heller1992saccharomycescerevisiaesec59 pages 2-3): L Heller, P Orlean, and WL Adair Jr. Saccharomyces cerevisiae sec59 cells are deficient in dolichol kinase activity. Proceedings of the National Academy of Sciences of the United States of America, 89 15:7013-6, Aug 1992. URL: https://doi.org/10.1073/pnas.89.15.7013, doi:10.1073/pnas.89.15.7013. This article has 85 citations and is from a highest quality peer-reviewed journal.
(ziogiene2024dolicholkinasesfrom pages 9-11): Danguole Ziogiene, Andrius Burdulis, Albertas Timinskas, Ruta Zinkeviciute, Emilija Vasiliunaite, Milda Norkiene, and Alma Gedvilaite. Dolichol kinases from yeast, nematode and human can replace each other and exchange their domains creating active chimeric enzymes in yeast. PLOS ONE, 19:e0313330, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0313330, doi:10.1371/journal.pone.0313330. This article has 1 citations and is from a peer-reviewed journal.
(choy2025exploringsmallmolecules pages 24-28): JL Choy. Exploring small molecules targeting downstream functions of the mevalonate biosynthesis pathway. Unknown journal, 2025.