DGUOK (Q16854) review notes

Human deoxyguanosine kinase, mitochondrial. Deep research via falcon was unavailable
(provider out of credits, HTTP 402); this review is grounded in the UniProt record,
the seeded GOA TSV, and the cached publications.

Core biology

• DGUOK is the purine arm of the mitochondrial deoxyribonucleoside salvage pathway.
  It phosphorylates the purine deoxyribonucleosides deoxyguanosine (dGuo) and
  deoxyadenosine (dAdo) (also deoxyinosine, arabinosyl-guanine, cladribine) to their
  monophosphates (dGMP, dAMP) inside the mitochondrial matrix, using ATP (or another
  NTP) as phosphate donor [PMID:8706825 "phosphorylation of purine deoxyribonucleosides in the"; PMID:17073823 "rate-limiting phosphorylation of the purine deoxynucleosides, using a nucleoside"].
• Highest efficiency for deoxyguanosine (EC 2.7.1.113); also acts on deoxyadenosine
  (EC 2.7.1.76) [UniProt CATALYTIC ACTIVITY, EC=2.7.1.113 / EC=2.7.1.76].
• Together with TK2 (pyrimidine arm), it supplies dNTPs for mtDNA replication in
  non-proliferating/post-mitotic tissues, where cytosolic de-novo dNTP synthesis is
  down-regulated PMID:11687801.
• Homodimer; structure solved as complex with dATP (PDB 2OCP) [UniProt SUBUNIT].
• DCK/DGK family; ~46-48% identity to cytosolic deoxycytidine kinase (DCK)
  [PMID:8692979; UniProt SIMILARITY].

Localisation

• Mitochondrion / mitochondrial matrix; nuclear-encoded with cleaved N-terminal
  mitochondrial transit peptide (residues 1-39) [UniProt SUBCELLULAR LOCATION; TRANSIT].
• The nucleus HDA annotation (PMID:21630459) is from a sperm-nucleus proteome
  catalogue (403 proteins co-isolated); not a validated functional localisation — treat
  as over-annotation / contaminant, not core.

Disease

• MTDPS3: hepatocerebral mitochondrial DNA depletion syndrome (infantile liver failure +
  neurologic features) [UniProt DISEASE MTDPS3; PMID:12205643, PMID:15639197].
• NCPH1: non-cirrhotic portal hypertension (N46S) [PMID:26874653, PMID:17073823].
• PEOB4: adult-onset progressive external ophthalmoplegia / mtDNA multiple deletions
  PMID:23043144.

Annotation-review reasoning highlights

• MF core: GO:0004138 deoxyguanosine kinase activity and GO:0004136 deoxyadenosine kinase
  activity — both strongly experimentally supported (EXP/IDA/TAS) and are the core MF.
• GO:0004137 deoxycytidine kinase activity (IBA only): DGUOK is purine-specific; dCyd
  is the substrate of the paralog DCK, not DGUOK. This IBA over-reaches from the family
  tree; MARK_AS_OVER_ANNOTATED (do not attribute dCK activity to DGUOK).
• GO:0019136 deoxynucleoside kinase activity (IEA): correct but generic parent; ACCEPT
  as a valid broad umbrella.
• GO:0005524 ATP binding (IEA): supported by structure/ligand binding; ACCEPT.
• GO:0005737 cytoplasm (IBA is_active_in): DGUOK is matrix-resident; the pan-family IBA
  reflects the cytosolic paralogs (DCK etc.). MARK_AS_OVER_ANNOTATED — the specific,
  correct compartment is mitochondrion/matrix.
• BP:
• GO:0106383 dAMP salvage (IDA, PMID:19221117): ACCEPT, core process (dAMP product).
• GO:0046122 purine deoxyribonucleoside metabolic process (IDA, PMID:8706825): ACCEPT,
  core process.
• GO:0008617 guanosine metabolic process (TAS, PMID:8692979): substrate is
  2'-deoxyguanosine, not guanosine; slightly mis-specified. MODIFY toward
  GO:0046122 (purine deoxyribonucleoside metabolic process).
• GO:1901135 carbohydrate derivative metabolic process (ARBA IEA): extremely generic
  umbrella; KEEP_AS_NON_CORE.
• GO:0010977 negative regulation of neuron projection development (Ensembl ortholog IEA
  from rat): not a demonstrated DGUOK function in human; over-propagated ortholog
  transfer. REMOVE (clearly wrong IEA inference).
• GO:0042775 mitochondrial ATP synthesis coupled electron transport (Ensembl ortholog
  IEA from rat): DGUOK is a salvage kinase, not an OXPHOS/ETC component; the mtDNA-
  depletion phenotype secondarily affects the respiratory chain but DGUOK is not
  involved_in electron transport. REMOVE (clearly wrong IEA inference).
• CC mitochondrion (multiple IBA/IEA/ISS/IDA/HTP/TAS) and mitochondrial matrix (TAS):
  ACCEPT; matrix is the most specific correct location.
• protein binding IPIs (PMID:33961781 BioPlex, PMID:40205054 cell-map): both interactome
  screens; WITH/FROM = DCK (P27707). Bare "protein binding" is uninformative;
  MARK_AS_OVER_ANNOTATED per policy (do not REMOVE IPI). DGUOK-DCK is a documented
  interaction in the UniProt INTERACTION block.