id: P23919
gene_symbol: DTYMK
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  DTYMK is thymidylate kinase (dTMP kinase; EC 2.7.4.9), a small cytosolic P-loop
  nucleotide kinase that catalyses the ATP- and Mg2+-dependent phosphorylation of
  thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP) (dTMP + ATP -> dTDP +
  ADP). This is the common penultimate step in the synthesis of the DNA building block
  dTTP: the de novo route (dUMP -> dTMP via thymidylate synthase) and the salvage route
  (thymidine -> dTMP via thymidine kinase) both converge on dTMP kinase, making it the
  bottleneck for dTTP biosynthesis; dTDP is subsequently phosphorylated to dTTP by
  nucleoside diphosphate kinase. Because dTTP cannot be generated by any bypass, the
  enzyme is essential for DNA replication and genome integrity; its expression and
  activity peak in S phase. The active enzyme is a homodimer and has been crystallised
  extensively in complex with dTMP/ATP analogues. It also activates thymidine-analogue
  prodrugs (e.g. zidovudine/AZT monophosphate). Biallelic loss-of-function variants cause
  a severe childhood-onset neurodegenerative disorder with progressive microcephaly.
alternative_products:
- name: '1'
  id: P23919-1
- name: '2'
  id: P23919-2
  sequence_note: VSP_054164
existing_annotations:
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetically inferred dTMP kinase activity, the defining molecular function of
      the thymidylate kinase family. This is correct and central for DTYMK and is
      independently supported by direct human experimental evidence.
    action: ACCEPT
    reason: >-
      dTMP kinase activity is the core, experimentally validated molecular function of the
      human enzyme, catalysing dTMP + ATP -> dTDP + ADP. The IBA call is consistent with
      abundant human EXP/IDA evidence.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "Catalyzes the phosphorylation of thymidine monophosphate"
    - reference_id: PMID:34918187
      supporting_text: "catalyzes the penultimate step in dTTP biosynthesis"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically inferred cytoplasmic localization. DTYMK is a small soluble kinase
      with no targeting signal and is described as cytosolic; cytoplasm is a correct,
      appropriately general compartment.
    action: ACCEPT
    reason: >-
      Consistent with the cytosolic localization of the enzyme reported by Reactome and
      with GOA cytosol (GO:0005829) annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0006233
    label: dTDP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetically inferred involvement in dTDP biosynthesis. This is the direct
      product-forming reaction of DTYMK (dTMP -> dTDP) and is a core process for the gene.
    action: ACCEPT
    reason: >-
      The immediate reaction product of DTYMK is dTDP; this is the enzyme's direct
      biosynthetic contribution and is experimentally supported.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "the immediate precursor for the"
    - reference_id: PMID:34918187
      supporting_text: "The thymidine de novo and salvage pathways converge at the point of the phosphorylation of dTMP to dTDP by dTMPK"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically inferred mitochondrial localization. The human enzyme is
      established as cytosolic, and this IBA call is propagated from a subset of orthologs;
      it is weakly supported and not the functionally relevant compartment for human DTYMK.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      DTYMK is a small soluble protein with no mitochondrial targeting sequence and is
      described as cytosolic deoxythymidylate kinase (Reactome). The mitochondrial IBA is
      over-propagated from the PANTHER family; the established and functionally relevant
      compartment is the cytosol/cytoplasm.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - COMPARTMENT_OR_COMPLEX_MISMATCH
    supported_by:
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0006227
    label: dUDP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetically inferred involvement in dUDP biosynthesis, reflecting the enzyme's
      ability to also phosphorylate dUMP to dUDP. This is a secondary/promiscuous activity,
      not the biological purpose of DTYMK, which is dTTP synthesis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Reactome records dUMP as an alternative substrate (dUMP or TMP + ATP -> dUDP or TDP),
      so dUDP formation is biochemically plausible, but the physiological role of DTYMK is
      the synthesis of thymidine nucleotides (dTDP/dTTP). Retain as a non-core, secondary
      activity rather than a core function.
    supported_by:
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "dUMP or TMP + ATP <=> dUDP or TDP + ADP [DTYMK]"
- term:
    id: GO:0006235
    label: dTTP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetically inferred involvement in dTTP biosynthesis. DTYMK performs the
      penultimate, common step of dTTP synthesis (dTMP -> dTDP), and is the essential
      bottleneck for making dTTP; this is a core biological process for the gene.
    action: ACCEPT
    reason: >-
      Both de novo and salvage routes converge on DTYMK, which is indispensable for dTTP
      biosynthesis and DNA replication; loss of function completely blocks dTTP synthesis.
    supported_by:
    - reference_id: PMID:34918187
      supporting_text: "This makes dTMPK the bottleneck for dTTP biosynthesis"
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "Pyrimidine metabolism; dTTP biosynthesis."
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically inferred nuclear localization, propagated from a subset of orthologs.
      The human enzyme is characterised as cytosolic, and nuclear localization is weakly
      supported.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      DTYMK has no nuclear-localization signal and is described as cytosolic (Reactome).
      Although dNTP synthesis serves nuclear DNA replication, the enzyme itself acts in the
      cytosol; the nuclear IBA is an over-propagation.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - COMPARTMENT_OR_COMPLEX_MISMATCH
    supported_by:
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic annotation of dTMP kinase activity from combined IEA methods (ARBA,
      InterPro, RHEA/EC mapping). This correctly captures the defining molecular function.
    action: ACCEPT
    reason: >-
      Matches the experimentally validated function and the RHEA:13517 / EC:2.7.4.9
      reaction; a correct, well-supported electronic call.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "Reaction=dTMP + ATP = dTDP + ADP"
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based electronic annotation of ATP binding. DTYMK is a P-loop ATP-dependent
      kinase; ATP binding is directly confirmed by crystal structures.
    action: ACCEPT
    reason: >-
      ATP is the phosphoryl donor and is bound at a defined P-loop site (structurally
      characterised, PMID:12614151); the electronic call is correct and supported by
      experimental evidence.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "Reaction=dTMP + ATP = dTDP + ADP"
- term:
    id: GO:0006233
    label: dTDP biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation of involvement in dTDP biosynthesis, matching the direct
      product-forming reaction of DTYMK.
    action: ACCEPT
    reason: >-
      dTDP is the immediate reaction product; the call is consistent with experimental and
      IBA evidence.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "the immediate precursor for the"
- term:
    id: GO:0006235
    label: dTTP biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation (UniPathway mapping) of involvement in dTTP biosynthesis,
      matching the UniProt pathway assignment "Pyrimidine metabolism; dTTP biosynthesis".
    action: ACCEPT
    reason: >-
      DTYMK performs the penultimate step of dTTP biosynthesis; the UniPathway-derived call
      is correct.
    supported_by:
    - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
      supporting_text: "Pyrimidine metabolism; dTTP biosynthesis."
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: EXP
  original_reference_id: PMID:2017365
  qualifier: enables
  review:
    summary: >-
      Human dTMP kinase cDNA cloned by functional complementation of a yeast dTMP kinase
      temperature-sensitive mutant; expression in yeast produces dTMP kinase activity,
      experimentally establishing the molecular function.
    action: ACCEPT
    reason: >-
      Direct experimental demonstration that the human gene product has dTMP kinase
      activity (phosphorylates dTMP to dTDP with ATP and Mg2+).
    supported_by:
    - reference_id: PMID:2017365
      supporting_text: "the cloned human cDNA, when expressed in yeast, produces dTMP kinase\n activity."
    - reference_id: PMID:2017365
      supporting_text: "(Deoxy)thymidylate (dTMP) kinase is an enzyme which phosphorylates dTMP to dTDP \nin the presence of ATP and magnesium."
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: EXP
  original_reference_id: PMID:34918187
  qualifier: enables
  review:
    summary: >-
      dTMPK enzyme activity measured directly in patient fibroblasts (severely reduced in
      individuals with biallelic DTYMK variants), and the enzyme is defined as catalysing
      the phosphorylation of dTMP to dTDP, confirming dTMP kinase activity for the human
      protein.
    action: ACCEPT
    reason: >-
      Provides human experimental (activity assay) evidence for dTMP kinase activity and
      links loss of this activity to disease; the affected step is the phosphorylation of
      dTMP to dTDP.
    supported_by:
    - reference_id: PMID:34918187
      supporting_text: "The thymidine de novo and salvage pathways converge at the point of the phosphorylation of dTMP to dTDP by dTMPK"
    - reference_id: PMID:34918187
      supporting_text: "dTMPK enzyme activity of the individual is significantly lower than those of the parents"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput mitochondrial proteomics (MitoCoP) call. DTYMK is an established
      cytosolic enzyme; a proteomics dataset hit likely reflects co-purification or
      dual/low-level reporting rather than a bona fide mitochondrial function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      DTYMK has no mitochondrial targeting presequence and its characterised, functional
      compartment is the cytosol (Reactome). A single HTP proteomics localization does not
      establish the mitochondrion as a functional site for this soluble kinase; treat as an
      over-annotation relative to the core cytosolic localization.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: "high-confidence proteome of >1,100 proteins"
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: IDA
  original_reference_id: PMID:12614151
  qualifier: enables
  review:
    summary: >-
      Structural and steady-state kinetic characterisation of human thymidylate kinase
      (TMPK) converting thymidine monophosphate analogues to the corresponding
      diphosphates, directly demonstrating dTMP kinase activity.
    action: ACCEPT
    reason: >-
      Crystal structures with substrate/product analogues plus steady-state kinetics
      directly establish the dTMP kinase catalytic activity of the human enzyme.
    supported_by:
    - reference_id: PMID:12614151
      supporting_text: "the enzyme thymidylate kinase (TMPK) of clinically important \nthymidine monophosphate analogues to the corresponding diphosphates"
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:12614151
  qualifier: enables
  review:
    summary: >-
      Crystal structures solved with ADP or the ATP analogue AppNHp bound at the
      phosphoryl-donor site, providing direct experimental evidence of ATP binding.
    action: ACCEPT
    reason: >-
      Structures with the ATP analogue at the phosphoryl-donor site directly demonstrate
      ATP binding by human thymidylate kinase.
    supported_by:
    - reference_id: PMID:12614151
      supporting_text: "with either ADP or the ATP analogue AppNHp \nat the phosphoryl donor site"
- term:
    id: GO:0006233
    label: dTDP biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:12614151
  qualifier: involved_in
  review:
    summary: >-
      Direct assay of the conversion of thymidine monophosphates to the corresponding
      diphosphates by human thymidylate kinase, supporting involvement in dTDP biosynthesis.
    action: ACCEPT
    reason: >-
      The reaction assayed produces the diphosphate (dTDP) from the monophosphate (dTMP),
      the direct biosynthetic contribution of DTYMK.
    supported_by:
    - reference_id: PMID:12614151
      supporting_text: "thymidine monophosphate analogues to the corresponding diphosphates"
- term:
    id: GO:0046105
    label: thymidine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:12614151
  qualifier: involved_in
  review:
    summary: >-
      Annotation to thymidine biosynthetic process. This mislabels the biology: DTYMK acts
      on the nucleotide dTMP (producing dTDP), not on the nucleoside thymidine, and the
      process it serves is dTDP/dTTP biosynthesis, not thymidine biosynthesis.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The paper characterises phosphorylation of thymidine monophosphate to the
      diphosphate; it does not establish biosynthesis of thymidine (the nucleoside). The
      more accurate process terms are dTDP biosynthetic process (GO:0006233) and dTTP
      biosynthetic process (GO:0006235), both already annotated. Treat this term as an
      over-annotation relative to the correctly captured dTDP/dTTP processes.
    supported_by:
    - reference_id: PMID:12614151
      supporting_text: "thymidine monophosphate analogues to the corresponding diphosphates"
- term:
    id: GO:0046105
    label: thymidine biosynthetic process
  evidence_type: TAS
  original_reference_id: PMID:8024690
  qualifier: involved_in
  review:
    summary: >-
      Author-statement annotation to thymidine biosynthetic process. As with the IDA above,
      the described activity is phosphorylation of dTMP to the diphosphate en route to dTTP,
      not biosynthesis of the nucleoside thymidine.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      DTYMK catalyses dTMP -> dTDP and is essential for dTTP synthesis, not for making
      thymidine; the correct process terms (dTDP/dTTP biosynthetic process) are already
      annotated. Over-annotation via a mismatched process term.
    supported_by:
    - reference_id: PMID:8024690
      supporting_text: "dTMP kinase (E.C.2.7.4.9.) catalyzes the phosphorylation of dTMP to the \ncorresponding diphosphate."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-73635
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement localizing DTYMK to the cytosol, consistent with
      the enzyme being a small soluble cytosolic kinase. This is the core, functionally
      relevant compartment.
    action: ACCEPT
    reason: >-
      Reactome explicitly describes cytosolic deoxythymidylate kinase; matches the
      established localization of the human enzyme.
    supported_by:
    - reference_id: Reactome:R-HSA-73635
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75126
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement (reverse reaction module) localizing DTYMK to the
      cytosol; duplicate of the cytosol call and equally correct.
    action: ACCEPT
    reason: >-
      Consistent with the cytosolic localization of the human enzyme described by Reactome.
    supported_by:
    - reference_id: Reactome:R-HSA-75126
      supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: IDA
  original_reference_id: PMID:8845311
  qualifier: enables
  review:
    summary: >-
      Characterisation of the (murine) thymidylate kinase gene, defining TMK as catalysing
      the essential conversion of dTMP to dTDP; supports the conserved dTMP kinase activity
      of the orthologous mammalian enzyme.
    action: ACCEPT
    reason: >-
      Establishes thymidylate kinase activity (dTMP -> dTDP) for the mammalian enzyme; the
      function is directly and abundantly supported for the human protein by other evidence.
    supported_by:
    - reference_id: PMID:8845311
      supporting_text: "Thymidylate kinase (TMK) catalyzes an essential reaction of converting dTMP to \ndTDP, leading to formation of the DNA precursor dTTP."
- term:
    id: GO:0004798
    label: dTMP kinase activity
  evidence_type: TAS
  original_reference_id: PMID:8024690
  qualifier: enables
  review:
    summary: >-
      Traceable-author-statement annotation of dTMP kinase activity for the human enzyme,
      defined as catalysing the phosphorylation of dTMP to the corresponding diphosphate.
    action: ACCEPT
    reason: >-
      Directly states the dTMP kinase catalytic activity of human dTMP kinase; concordant
      with the EXP/IDA evidence.
    supported_by:
    - reference_id: PMID:8024690
      supporting_text: "dTMP kinase (E.C.2.7.4.9.) catalyzes the phosphorylation of dTMP to the \ncorresponding diphosphate."
core_functions:
- description: >-
    Thymidylate (dTMP) kinase activity: ATP- and Mg2+-dependent phosphorylation of dTMP to
    dTDP, the common penultimate step of dTTP synthesis shared by the de novo and salvage
    routes; essential for supplying dTTP for DNA replication.
  molecular_function:
    id: GO:0004798
    label: dTMP kinase activity
  directly_involved_in:
  - id: GO:0006235
    label: dTTP biosynthetic process
  supported_by:
  - reference_id: file:human/DTYMK/DTYMK-uniprot.txt
    supporting_text: "Catalyzes the phosphorylation of thymidine monophosphate"
  - reference_id: PMID:34918187
    supporting_text: "This makes dTMPK the bottleneck for dTTP biosynthesis"
- description: >-
    Formation of dTDP as the direct reaction product of dTMP phosphorylation, the immediate
    biosynthetic output of DTYMK en route to dTTP.
  molecular_function:
    id: GO:0004798
    label: dTMP kinase activity
  directly_involved_in:
  - id: GO:0006233
    label: dTDP biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:34918187
    supporting_text: "The thymidine de novo and salvage pathways converge at the point of the phosphorylation of dTMP to dTDP by dTMPK"
  - reference_id: Reactome:R-HSA-73635
    supporting_text: "Cytosolic deoxythymidylate kinase (DTYMK) catalyzes the reversible reaction"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12614151
  title: 'Structures of human thymidylate kinase in complex with prodrugs: implications
    for the structure-based design of novel compounds.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Structural/kinetic characterisation of human TMPK; directly supports dTMP kinase
      activity, ATP binding, and dTDP formation. Abstract quotes verified verbatim.
- id: PMID:2017365
  title: Molecular cloning and expression of the human deoxythymidylate kinase gene
    in yeast.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cloned human dTMP kinase; complementation of yeast cdc8-type mutant and dTMP kinase
      activity on expression establish the molecular function. Quotes verified verbatim.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      MitoCoP high-throughput mitochondrial proteomics dataset; source of the HTP
      mitochondrion call. DTYMK is not discussed in the prose; the enzyme is established as
      cytosolic, so this localization is treated as an over-annotation.
- id: PMID:34918187
  title: DTYMK is essential for genome integrity and neuronal survival.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes DTYMK as the penultimate step of dTTP biosynthesis at the convergence of
      de novo and salvage pathways, with patient-fibroblast activity assays and disease
      linkage (CONPM). Full text available; quotes verified verbatim.
- id: PMID:8024690
  title: 'Human dTMP kinase: gene expression and enzymatic activity coinciding with
    cell cycle progression and cell growth.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Human dTMP kinase catalysing dTMP phosphorylation; S-phase-regulated expression and
      activity. Supports MF and cell-cycle context. Quotes verified verbatim.
- id: PMID:8845311
  title: Molecular characterization of the murine thymidylate kinase gene.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Murine ortholog; defines TMK as converting dTMP to dTDP toward dTTP and shows
      G0-to-S cell-cycle regulation. Supports the conserved mammalian function. Quotes
      verified verbatim.
- id: Reactome:R-HSA-73635
  title: dUMP or TMP + ATP <=> dUDP or TDP + ADP [DTYMK]
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction defining cytosolic DTYMK acting on dTMP (and, as an alternative
      substrate, dUMP). Supports cytosol localization and the dUDP secondary activity.
- id: Reactome:R-HSA-75126
  title: dUDP or TDP + ADP <=> dUMP or TMP + ATP [DTYMK]
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reverse-direction Reactome reaction for cytosolic DTYMK; supports cytosol
      localization.
- id: file:human/DTYMK/DTYMK-uniprot.txt
  title: UniProtKB entry P23919 (KTHY_HUMAN), thymidylate kinase
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      UniProt curated record; FUNCTION, CATALYTIC ACTIVITY (RHEA:13517), PATHWAY, and
      SUBUNIT fields support the core function and localization. Quotes verified verbatim.