TYMP

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009032 thymidine phosphorylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred thymidine phosphorylase activity, the defining and experimentally validated molecular function of TYMP. This is the core MF. Reason: TYMP is thymidine phosphorylase (EC 2.4.2.4), catalyzing the reversible phosphorolysis of thymidine to thymine and 2-deoxy-alpha-D-ribose 1-phosphate. The IBA propagation across the thymidine/pyrimidine-nucleoside phosphorylase family (PTN000054065) matches direct enzymatic evidence for the human protein. Supporting Evidence: PMID:1590793 PD-ECGF has thymidine phosphorylase activity file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: TYMP is a cytosolic enzyme; phylogenetic inference of cytosolic localization is consistent with Reactome and UniProt. Reason: Thymidine phosphorylase acts in the cytosol, where it participates in cytosolic pyrimidine salvage/catabolism. This is corroborated by Reactome (both catalytic reactions localized to the cytosol) and by the enzyme lacking any organellar targeting signal. Supporting Evidence: Reactome:R-HSA-112265 Cytosolic thymidine phosphorylase (TYMP) catalyzes the reversible reactions of thymidine or deoxyuridine with orthophosphate to form thymine or uracil and 2-deoxy-D-ribose 1-phosphate.
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	IEA GO_REF:0000002	REMOVE	Summary: Electronic InterPro2GO mapping (IPR000053) assigning glycogen/starch phosphorylase activity. This is incorrect for TYMP. Reason: GO:0004645 (1,4-alpha-oligoglucan phosphorylase activity, i.e. glycogen/starch phosphorylase) is a distinct enzyme acting on alpha-1,4-glucan polysaccharides, not on nucleosides. TYMP is a pyrimidine-nucleoside phosphorylase (EC 2.4.2.4) that phosphorolyses thymidine/deoxyuridine; it has no activity on oligoglucans. This is a demonstrably wrong IEA arising from the InterPro entry being over-broad relative to the actual catalytic specificity; the correct MF is GO:0009032. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:0006206 pyrimidine nucleobase metabolic process	IEA GO_REF:0000002	ACCEPT	Summary: TYMP produces the pyrimidine nucleobase thymine (and uracil from deoxyuridine) and, in the reverse direction, consumes them, so it participates in pyrimidine nucleobase metabolism. Reason: The phosphorolysis reaction produces thymine/uracil from thymidine/deoxyuridine (and the reverse builds nucleosides from nucleobases), placing TYMP directly in pyrimidine nucleobase metabolism. This is an accurate InterPro2GO mapping. Supporting Evidence: Reactome:R-HSA-112265 Cytosolic thymidine phosphorylase (TYMP) catalyzes the reversible reactions of thymidine or deoxyuridine with orthophosphate to form thymine or uracil and 2-deoxy-D-ribose 1-phosphate.
GO:0006213 pyrimidine nucleoside metabolic process	IEA GO_REF:0000002	ACCEPT	Summary: TYMP metabolizes the pyrimidine nucleosides thymidine and 2'-deoxyuridine; this is the core biological process for the enzyme and is well supported by the IDA/IMP experimental annotations below. Reason: Phosphorolysis of thymidine/2'-deoxyuridine is precisely pyrimidine nucleoside metabolism. This InterPro2GO mapping is accurate and duplicates the experimentally supported (IDA, IMP) annotations to the same term. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:0009032 thymidine phosphorylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of thymidine phosphorylase activity via EC 2.4.2.4 / RHEA:16037. Correct and matches the experimental IDA/IMP annotations. Reason: This IEA mapping (ARBA/EC:2.4.2.4/RHEA:16037) reproduces the core, experimentally validated molecular function of TYMP. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Reaction=thymidine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate +
GO:0016154 pyrimidine-nucleoside phosphorylase activity	IEA GO_REF:0000002	ACCEPT	Summary: Parent MF term for TYMP's activity. TYMP phosphorolyses not only thymidine but also 2'-deoxyuridine, so it genuinely has pyrimidine-nucleoside phosphorylase activity; the more specific thymidine phosphorylase activity term is preferred as the core annotation. Reason: Accurate InterPro2GO mapping. TYMP acts on multiple pyrimidine 2'-deoxyribonucleosides (thymidine and 2'-deoxyuridine), justifying this broader activity term alongside the specific GO:0009032. Supporting Evidence: Reactome:R-HSA-112265 Cytosolic thymidine phosphorylase (TYMP) catalyzes the reversible reactions of thymidine or deoxyuridine with orthophosphate to form thymine or uracil and 2-deoxy-D-ribose 1-phosphate.
GO:0016757 glycosyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Very general MF derived from the glycosyltransferase-family-3 (IPR000312) fold. Not wrong in the broadest sense (a pentosyl group is transferred) but uninformative relative to the specific thymidine phosphorylase activity. Reason: TYMP belongs to the glycosyltransferase family 3 fold, so this high-level term is technically compatible, but it conveys no useful functional information beyond the specific and experimentally supported GO:0009032. Retain the specific MF terms instead. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:0016763 pentosyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: General parent term (pentosyltransferase) above thymidine/pyrimidine-nucleoside phosphorylase activity. Correct in ancestry but too broad to be informative. Reason: Thymidine phosphorylase activity (GO:0009032) is a subtype of pentosyltransferase activity (transfer of the 2-deoxyribose pentosyl group), so this term is an ancestor rather than a distinct function. The specific terms should carry the annotation. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Reaction=thymidine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate +
GO:0055086 nucleobase-containing small molecule metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: High-level ARBA-derived BP term. True but far more general than the specific pyrimidine nucleoside/nucleobase metabolic process terms. Reason: Thymidine, deoxyuridine, thymine and uracil are nucleobase-containing small molecules, so the term is an accurate ancestor, but it is uninformative relative to GO:0006213 and GO:0006206 which are already annotated. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:0072527 pyrimidine-containing compound metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: General ARBA-derived parent of pyrimidine nucleoside/nucleobase metabolic process. Correct but too broad. Reason: This is a direct ancestor of the more specific pyrimidine nucleoside (GO:0006213) and nucleobase (GO:0006206) metabolic process terms that already capture TYMP's role; the broad term adds no specific information. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Catalyzes the reversible phosphorolysis of thymidine
GO:1901135 carbohydrate derivative metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very general ARBA-derived BP term. The reaction does generate the sugar-phosphate 2-deoxy-alpha-D-ribose 1-phosphate, but this broad term is uninformative. Reason: The 2-deoxy-alpha-D-ribose 1-phosphate product is a carbohydrate derivative, so the term is technically compatible, but it is far too general to convey TYMP's function; the specific pyrimidine metabolic process terms are preferred. Supporting Evidence: file:human/TYMP/TYMP-uniprot.txt Reaction=thymidine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate +
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare 'protein binding' from a high-throughput binary interactome screen (HuRI; interactions with MESD/Q14696 and ZMYND12/Q9H0C1). Uninformative as a molecular function. Reason: GO:0005515 protein binding does not describe a specific molecular function and conveys nothing about TYMP's biology; the reported partners are from a systematic yeast-two-hybrid interactome map with no established functional consequence for TYMP. Per curation policy this is retained but marked as an over-annotation rather than removed. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions
GO:0006213 pyrimidine nucleoside metabolic process	IDA PMID:1590793 Platelet-derived endothelial cell growth factor has thymidin...	ACCEPT	Summary: Direct demonstration that recombinant human PD-ECGF (TYMP) has thymidine phosphorylase activity, i.e. metabolizes the pyrimidine nucleoside thymidine. Core biological process. Reason: Usuki et al. showed recombinant human PD-ECGF phosphorolyses thymidine, directly establishing TYMP's participation in pyrimidine nucleoside metabolism. Supporting Evidence: PMID:1590793 PD-ECGF has thymidine phosphorylase activity
GO:0006213 pyrimidine nucleoside metabolic process	IMP PMID:9924029 Thymidine phosphorylase gene mutations in MNGIE, a human mit...	ACCEPT	Summary: Loss-of-function TYMP mutations in MNGIE patients reduce TP activity to <5% of controls and are linked to aberrant thymidine metabolism and mtDNA instability, confirming TYMP's in vivo role in pyrimidine nucleoside metabolism. Reason: The MNGIE genetic evidence (mutation phenotype) demonstrates that TYMP is required for normal pyrimidine (thymidine/deoxyuridine) metabolism in humans; its loss causes thymidine accumulation that destabilizes mitochondrial DNA. Supporting Evidence: PMID:9924029 loss-of-function mutations in TP cause the disease PMID:9924029 aberrant thymidine metabolism, leading to
GO:0009032 thymidine phosphorylase activity	IDA PMID:1590793 Platelet-derived endothelial cell growth factor has thymidin...	ACCEPT	Summary: Direct experimental demonstration that recombinant human PD-ECGF/TYMP has thymidine phosphorylase activity. This is the defining, core molecular function. Reason: Usuki et al. assayed recombinant human PD-ECGF and showed it possesses thymidine phosphorylase activity, establishing EC 2.4.2.4 for the human protein. Supporting Evidence: PMID:1590793 PD-ECGF has thymidine phosphorylase activity
GO:0042803 protein homodimerization activity	IDA PMID:1590793 Platelet-derived endothelial cell growth factor has thymidin...	ACCEPT	Summary: TYMP is a homodimer; recombinant human PD-ECGF was shown to occur as a 90 kDa homodimer, and multiple crystal structures confirm the homodimeric assembly. Reason: Homodimerization is well established biochemically (gel chromatography of recombinant PD-ECGF, PMID:1590793) and structurally (X-ray structures, UniProt SUBUNIT). This is the functional oligomeric state of the active enzyme. Supporting Evidence: PMID:1590793 recombinant human PD-ECGF occurs as a 90 kDa homodimer file:human/TYMP/TYMP-uniprot.txt SUBUNIT: Homodimer
GO:0009032 thymidine phosphorylase activity	IMP PMID:9924029 Thymidine phosphorylase gene mutations in MNGIE, a human mit...	ACCEPT	Summary: MNGIE mutations reduce leukocyte thymidine phosphorylase (TP) activity to <5% of controls, showing TYMP is the enzyme responsible for this activity in vivo. Core molecular function. Reason: The mutation phenotype (near-total loss of TP activity in patients with biallelic TYMP mutations) provides genetic (IMP) evidence that TYMP enables thymidine phosphorylase activity. Supporting Evidence: PMID:9924029 TP activity PMID:9924029 loss-of-function mutations in TP cause the disease
GO:0005829 cytosol	TAS Reactome:R-HSA-112265	ACCEPT	Summary: Reactome localizes TYMP's catalytic reaction to the cytosol. Consistent with the IBA cytosol annotation. Reason: TYMP is a cytosolic enzyme carrying out cytosolic pyrimidine salvage and catabolism, as curated by Reactome. Supporting Evidence: Reactome:R-HSA-112265 Cytosolic thymidine phosphorylase (TYMP) catalyzes the reversible reactions of thymidine or deoxyuridine with orthophosphate to form thymine or uracil and 2-deoxy-D-ribose 1-phosphate.
GO:0005829 cytosol	TAS Reactome:R-HSA-112266	ACCEPT	Summary: Reactome localizes the reverse (synthetic) TYMP reaction to the cytosol. Consistent with the IBA and other cytosol annotations. Reason: The reverse reaction (nucleobase + deoxyribose-1-phosphate -> nucleoside) catalyzed by TYMP also occurs in the cytosol per Reactome. Supporting Evidence: Reactome:R-HSA-112266 Cytosolic thymidine phosphorylase (TYMP) catalyzes the reversible reactions of thymine or uracil with 2-deoxy-D-ribose 1-phosphate to form thymidine or deoxyuridine and orthiophosphate.
GO:0046104 thymidine metabolic process	IDA PMID:1590793 Platelet-derived endothelial cell growth factor has thymidin...	NEW	Summary: The most specific biological process for TYMP - metabolism of thymidine itself, via its phosphorolysis to thymine and 2-deoxy-alpha-D-ribose 1-phosphate. Proposed as a more specific complement to the existing pyrimidine nucleoside metabolic process annotations. Reason: TYMP directly metabolizes thymidine (its eponymous substrate); GO:0046104 thymidine metabolic process is a more precise descendant of the annotated GO:0006213 pyrimidine nucleoside metabolic process and better captures the core biology. Supported by direct enzymatic evidence and the MNGIE thymidine-accumulation phenotype. Supporting Evidence: PMID:1590793 PD-ECGF has thymidine phosphorylase activity PMID:9924029 aberrant thymidine metabolism, leading to

Gene Description

Existing Annotations Review

Core Functions

Thymidine phosphorylase activity - catalyzes the reversible phosphorolysis of thymidine (and 2'-deoxyuridine) to thymine (uracil) + 2-deoxy-alpha-D-ribose 1-phosphate, the defining enzymatic function of TYMP.

References

📚 Additional Documentation

Notes

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