DGUOK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004136 deoxyadenosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of deoxyadenosine kinase activity. This is a genuine, experimentally confirmed activity of DGUOK: recombinant human dGK phosphorylates deoxyadenosine (EC 2.7.1.76) in addition to its preferred substrate deoxyguanosine. Correct and part of the core molecular function. Reason: DGUOK phosphorylates deoxyadenosine as well as deoxyguanosine, an activity demonstrated directly for the recombinant human enzyme and encoded as EC 2.7.1.76 in UniProt. Supporting Evidence: PMID:8706825 phosphorylation of dGuo, arabinosyl guanine, dAdo, 2-chloro-2'-deoxyadenosine file:human/DGUOK/DGUOK-uniprot.txt EC=2.7.1.76
GO:0004137 deoxycytidine kinase activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) assignment of deoxycytidine kinase activity. DGUOK is a purine-specific deoxyribonucleoside kinase; deoxycytidine is the substrate of the paralog deoxycytidine kinase (DCK), not DGUOK. This IBA over-reaches from the shared DCK/DGK family tree onto DGUOK. Reason: Human DGUOK efficiently phosphorylates the purine deoxyribonucleosides deoxyguanosine and deoxyadenosine, whereas pyrimidine deoxyribonucleosides (deoxycytidine) are handled by other kinases; deoxycytidine kinase activity is not a demonstrated DGUOK function and is inappropriately transferred across the family tree. The related paralog DCK carries this activity. The seeding PANTHER family (PTN002236991) groups purine-specific DGUOK/DGK orthologs together with the broader-specificity deoxycytidine kinase (DCK) clade, so deoxycytidine (a DCK substrate) kinase activity leaks onto DGUOK. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002236991 · DCK/DGK deoxyribonucleoside kinase family node UniProtKB:P27707 · DCK (deoxycytidine kinase paralog carrying dCyd activity) Supporting Evidence: PMID:11687801 efficiently phosphorylates PMID:11687801 deoxyguanosine and deoxyadenosine, whereas TK2 phosphorylates
GO:0004138 deoxyguanosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of deoxyguanosine kinase activity. This is the defining, best-supported molecular function of DGUOK (EC 2.7.1.113): it phosphorylates deoxyguanosine with highest efficiency. Core function. Reason: Deoxyguanosine kinase activity is the primary, experimentally established catalytic activity of DGUOK and is consistent across the phylogeny; this is the core molecular function. Supporting Evidence: PMID:11687801 efficiently phosphorylates file:human/DGUOK/DGUOK-uniprot.txt EC=2.7.1.113
GO:0005737 cytoplasm	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) is_active_in cytoplasm. DGUOK is a mitochondrial matrix-resident enzyme (nuclear-encoded, imported via a cleaved N-terminal transit peptide). The pan-family IBA reflects the cytosolic paralogs (e.g. DCK) rather than DGUOK itself; the specific, correct compartment is the mitochondrion / mitochondrial matrix. Reason: DGUOK acts in the mitochondrial matrix, not the general cytoplasm; the cytoplasm IBA is transferred from cytosolic family members and is superseded by the more specific and experimentally supported mitochondrial/matrix localisation. The seeding family node (PTN000053758) includes cytosolic deoxyribonucleoside kinases (e.g. DCK), whose cytoplasmic localisation does not apply to the matrix-targeted DGUOK. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000053758 · deoxyribonucleoside kinase family node (mixed cytosolic/mitochondrial members) UniProtKB:P27707 · DCK (cytosolic paralog) Supporting Evidence: PMID:8706825 phosphorylation of purine deoxyribonucleosides in the file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) is_active_in mitochondrion. Correct: DGUOK is a mitochondrial deoxyribonucleoside salvage enzyme acting in the matrix. Reason: DGUOK is localised to and active within the mitochondrion (matrix), consistent with its role in supplying dNTP precursors for mtDNA replication. Supporting Evidence: PMID:8706825 phosphorylation of purine deoxyribonucleosides in the file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0004136 deoxyadenosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated EC/RHEA-based (IEA) assignment of deoxyadenosine kinase activity (EC 2.7.1.76, RHEA:23452). Consistent with the experimentally verified activity. Reason: Mapping matches the UniProt EC 2.7.1.76 catalytic activity and the experimentally demonstrated deoxyadenosine phosphorylation by DGUOK. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt EC=2.7.1.76
GO:0004138 deoxyguanosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated EC/RHEA-based (IEA) assignment of deoxyguanosine kinase activity (EC 2.7.1.113, RHEA:19201). Matches the core, experimentally verified activity. Reason: Mapping matches the UniProt EC 2.7.1.113 catalytic activity and the primary experimentally demonstrated function of DGUOK. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt EC=2.7.1.113
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based (IEA) ATP binding. DGUOK uses ATP (or another NTP) as the phosphate donor; the crystal structure defines discrete ATP-binding residues (P-loop / glycine-rich motif). Correct supporting molecular function. Reason: ATP binding is required for the phosphotransfer reaction and is directly supported by the ligand-binding residues resolved in the DGUOK crystal structure. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt Reaction=2'-deoxyguanosine + ATP = dGMP + ADP + H(+)
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: UniProt Subcellular Location mapping (IEA) to mitochondrion. Correct primary localisation of DGUOK. Reason: DGUOK is a nuclear-encoded mitochondrial matrix protein; the SubCell mapping is accurate. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0019136 deoxynucleoside kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (IEA) assignment of the broad parent term deoxynucleoside kinase activity. Correct but generic: DGUOK is a deoxyribonucleoside (deoxyguanosine/ deoxyadenosine) kinase. Valid umbrella term above the specific EC-based terms. Reason: DGUOK is a deoxyribonucleoside kinase; this parent term is accurate though less informative than the specific deoxyguanosine/deoxyadenosine kinase activities. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt Belongs to the DCK/DGK family
GO:1901135 carbohydrate derivative metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning (IEA) assignment of a very high-level process term. Nucleotides/nucleosides are carbohydrate derivatives, so this is technically correct but far too generic to be informative about DGUOK's function. Reason: The term is a broad, non-specific umbrella; it is not wrong (deoxyribonucleotides are carbohydrate derivatives) but conveys nothing about the specific deoxyribonucleoside salvage role. Retained as non-core. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt phosphorylation of purine deoxyribonucleosides in the
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IntAct/BioPlex high-throughput AP-MS interaction (WITH/FROM DCK, P27707). "Protein binding" is uninformative about molecular function; the underlying DGUOK-DCK interaction is documented in UniProt but does not describe a distinct molecular function of DGUOK. Reason: Bare protein binding provides no functional information and derives from a proteome-scale AP-MS screen; per curation policy it is marked as over-annotated rather than removed. The captured DCK interaction is recorded in the UniProt INTERACTION block. Supporting Evidence: PMID:33961781 suggesting functions for thousands of proteins file:human/DGUOK/DGUOK-uniprot.txt Q16854; P27707: DCK;
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: IntAct interaction from a genome-scale multimodal cell-map study (WITH/FROM DCK, P27707). As with the BioPlex IPI, "protein binding" is a non-informative molecular-function term. Reason: Uninformative bare protein-binding term from a high-throughput interactome map; marked as over-annotated (not removed) per policy. The DGUOK-DCK interaction it captures is already recorded in UniProt. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt Q16854; P27707: DCK;
GO:0010977 negative regulation of neuron projection development	IEA GO_REF:0000107	REMOVE	Summary: Ensembl-Compara ortholog transfer (IEA) from a rat gene of a neuronal developmental process. DGUOK is a housekeeping mitochondrial salvage kinase; there is no evidence that it functions in negative regulation of neuron projection development in human. This is an over-propagated, biologically implausible electronic inference. Reason: No experimental or family-level support for DGUOK participating in neuron projection development; the annotation is an automated ortholog transfer that does not reflect DGUOK's established molecular/cellular role. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt phosphorylation of purine deoxyribonucleosides in the
GO:0042775 mitochondrial ATP synthesis coupled electron transport	IEA GO_REF:0000107	REMOVE	Summary: Ensembl-Compara ortholog transfer (IEA) from a rat gene, assigning DGUOK to the respiratory-chain electron-transport process. DGUOK is a deoxyribonucleoside salvage kinase, not an OXPHOS/electron-transport-chain component; although DGUOK deficiency secondarily impairs the mtDNA-encoded respiratory chain (via mtDNA depletion), DGUOK itself is not involved_in electron transport. Reason: DGUOK does not participate in mitochondrial electron transport; any respiratory chain deficit in DGUOK disease is a downstream consequence of mtDNA depletion, not a direct role. This is an incorrect over-propagated electronic inference. Supporting Evidence: PMID:11687801 mtDNA synthesis depends solely on the mitochondrial
GO:0004136 deoxyadenosine kinase activity	EXP PMID:17073823 Kinetic properties of mutant deoxyguanosine kinase in a case...	ACCEPT	Summary: Experimental (EXP) deoxyadenosine kinase activity. Kinetic characterisation of normal and mutant DGUOK in mitochondrial preparations measured activity with deoxyadenosine as a phosphate acceptor, confirming dAdo phosphorylation. Reason: Direct kinetic assays of DGUOK with deoxyadenosine as substrate confirm this catalytic activity; it is part of the core molecular function (purine arm). Supporting Evidence: PMID:17073823 rate-limiting phosphorylation of the purine deoxynucleosides, using a nucleoside
GO:0004136 deoxyadenosine kinase activity	EXP PMID:8692979 Cloning and expression of human deoxyguanosine kinase cDNA.	ACCEPT	Summary: Experimental (EXP) deoxyadenosine kinase activity from the original cloning/ expression study; recombinant human dGK showed the same substrate specificity as purified mitochondrial dGK, which phosphorylates purine deoxyribonucleosides including deoxyadenosine. Reason: The cloned, expressed enzyme reproduced the mitochondrial dGK substrate specificity (purine deoxyribonucleosides), supporting deoxyadenosine kinase activity as a core function. Supporting Evidence: PMID:8692979 with the same substrate specificity as described for the mitochondrial
GO:0004136 deoxyadenosine kinase activity	EXP PMID:8706825 Cloning and expression of human mitochondrial deoxyguanosine...	ACCEPT	Summary: Experimental (EXP) deoxyadenosine kinase activity. Recombinant human dGK catalysed efficient phosphorylation of dAdo (and 2-chloro-2'-deoxyadenosine), confirming deoxyadenosine kinase activity. Reason: Purified recombinant DGUOK phosphorylates deoxyadenosine directly; core molecular function of the purine salvage arm. Supporting Evidence: PMID:8706825 phosphorylation of dGuo, arabinosyl guanine, dAdo, 2-chloro-2'-deoxyadenosine
GO:0004138 deoxyguanosine kinase activity	EXP PMID:11687801 Mutant mitochondrial thymidine kinase in mitochondrial DNA d...	ACCEPT	Summary: Experimental (EXP) deoxyguanosine kinase activity. Human dGK is described as efficiently phosphorylating deoxyguanosine (and deoxyadenosine) as one of the two mitochondrial deoxyribonucleoside kinases. Core molecular function. Reason: Deoxyguanosine kinase activity is the primary, experimentally established function of DGUOK. Supporting Evidence: PMID:11687801 deoxyguanosine and deoxyadenosine, whereas TK2 phosphorylates
GO:0004138 deoxyguanosine kinase activity	EXP PMID:17073823 Kinetic properties of mutant deoxyguanosine kinase in a case...	ACCEPT	Summary: Experimental (EXP) deoxyguanosine kinase activity from kinetic characterisation of normal and mutant DGUOK in mitochondrial preparations, with deoxyguanosine as phosphate acceptor. Confirms the core catalytic activity. Reason: Direct kinetic assay of DGUOK activity with deoxyguanosine substrate; the rate-limiting phosphorylation step of the purine salvage arm. Supporting Evidence: PMID:17073823 rate-limiting phosphorylation of the purine deoxynucleosides, using a nucleoside
GO:0004138 deoxyguanosine kinase activity	EXP PMID:23043144 Next-generation sequencing reveals DGUOK mutations in adult ...	ACCEPT	Summary: Experimental (EXP) deoxyguanosine kinase activity. DGUOK mutations in patients impaired muscle DGUOK activity and protein stability, confirming that the encoded protein carries deoxyguanosine kinase activity. Reason: Patient DGUOK variants reduced measured DGUOK enzymatic activity, corroborating the core deoxyguanosine kinase function. Supporting Evidence: PMID:23043144 DGUOK activity and protein stability
GO:0005739 mitochondrion	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS) transfer of mitochondrial localisation from the mouse ortholog (Q9QX60). Consistent with the experimentally established mitochondrial localisation of DGUOK. Reason: DGUOK localises to mitochondria; the ISS transfer is accurate and corroborated by multiple independent lines of evidence. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput (HTP) localisation from a quantitative high-confidence human mitochondrial proteome study (MitoCoP). Supports DGUOK as a bona fide mitochondrial protein. Reason: DGUOK is recovered in a high-confidence mitochondrial proteome, consistent with its established mitochondrial matrix localisation. Supporting Evidence: file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005739 mitochondrion	IDA PMID:19221117 In vitro supplementation with dAMP/dGMP leads to partial res...	ACCEPT	Summary: Direct-assay (IDA) is_active_in mitochondrion. DGUOK-deficient patient cells were studied for mtDNA content and rescue by dAMP/dGMP supplementation, consistent with DGUOK acting within mitochondria on the mtDNA salvage pathway. Reason: DGUOK functions within mitochondria as part of the mtDNA-supporting salvage pathway, consistent with the experimental context. Supporting Evidence: PMID:19221117 rescue of mtDNA depletion in DGUOK deficiency
GO:0106383 dAMP salvage	IDA PMID:19221117 In vitro supplementation with dAMP/dGMP leads to partial res...	ACCEPT	Summary: Direct-assay (IDA) involvement in dAMP salvage. DGUOK phosphorylates deoxyadenosine to dAMP; supplementation with dAMP/dGMP significantly and reproducibly rescued mtDNA depletion in DGUOK-deficient cells, tying DGUOK to salvage production of dAMP. Core biological process. Reason: DGUOK generates dAMP from deoxyadenosine as part of the mitochondrial purine deoxyribonucleoside salvage pathway; this is a core process for the enzyme. Supporting Evidence: PMID:19221117 Supplementation with dAMP/dGMP leads to a significant and reproducible PMID:19221117 rescue of mtDNA depletion in DGUOK deficiency
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: High-throughput proteomics (HDA) detecting DGUOK in an isolated human sperm nucleus preparation (a 403-protein catalogue). DGUOK is a mitochondrial matrix enzyme; nuclear detection in a specialised sperm proteome most likely reflects residual co-isolation rather than a functional nuclear localisation. Reason: The nuclear assignment comes from a single specialised sperm-nucleus proteome and is inconsistent with DGUOK's well-established mitochondrial matrix localisation and function; it is treated as an over-annotation rather than a core location. Supporting Evidence: PMID:21630459 sperm nuclei were obtained file:human/DGUOK/DGUOK-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-74207	ACCEPT	Summary: Reactome (TAS) localisation to the mitochondrial matrix, the most specific and correct compartment for DGUOK, where purine deoxyribonucleoside salvage occurs. Reason: DGUOK phosphorylates purine deoxyribonucleosides in the mitochondrial matrix; this is the precise, correct subcellular location. Supporting Evidence: PMID:8706825 phosphorylation of purine deoxyribonucleosides in the
GO:0004138 deoxyguanosine kinase activity	IDA PMID:8706825 Cloning and expression of human mitochondrial deoxyguanosine...	ACCEPT	Summary: Direct-assay (IDA) deoxyguanosine kinase activity. Purified recombinant human dGK efficiently phosphorylated deoxyguanosine, directly demonstrating the core catalytic activity. Reason: Enzyme-assay evidence for deoxyguanosine phosphorylation by DGUOK; the defining molecular function. Supporting Evidence: PMID:8706825 phosphorylation of dGuo, arabinosyl guanine, dAdo, 2-chloro-2'-deoxyadenosine
GO:0046122 purine deoxyribonucleoside metabolic process	IDA PMID:8706825 Cloning and expression of human mitochondrial deoxyguanosine...	ACCEPT	Summary: Direct-assay (IDA) involvement in purine deoxyribonucleoside metabolism. DGUOK is responsible for phosphorylation of purine deoxyribonucleosides (deoxyguanosine, deoxyadenosine, deoxyinosine) in the mitochondrial matrix, the salvage arm that feeds mtDNA precursor supply. Core biological process. Reason: DGUOK phosphorylates purine deoxyribonucleosides as the committed salvage step; this accurately captures the enzyme's core metabolic process. Supporting Evidence: PMID:8706825 phosphorylation of purine deoxyribonucleosides in the
GO:0004138 deoxyguanosine kinase activity	TAS PMID:8692979 Cloning and expression of human deoxyguanosine kinase cDNA.	ACCEPT	Summary: Author-statement (TAS) deoxyguanosine kinase activity from the original cloning paper, which reported that the expressed cDNA encodes a protein with the same substrate specificity as mitochondrial dGK (EC 2.7.1.113). Core function. Reason: Corroborates the core deoxyguanosine kinase activity of DGUOK. Supporting Evidence: PMID:8692979 with the same substrate specificity as described for the mitochondrial
GO:0005739 mitochondrion	TAS PMID:8692979 Cloning and expression of human deoxyguanosine kinase cDNA.	ACCEPT	Summary: Author-statement (TAS) mitochondrial localisation. The cloning paper described a protein with an N-terminal mitochondrial translocation signal and matching the mitochondrial dGK. Correct localisation. Reason: DGUOK carries a mitochondrial targeting/transit sequence and is the mitochondrial deoxyguanosine kinase; the mitochondrial localisation is well supported. Supporting Evidence: PMID:8692979 N terminus of the deduced amino
GO:0008617 guanosine metabolic process	TAS PMID:8692979 Cloning and expression of human deoxyguanosine kinase cDNA.	MODIFY	Summary: Author-statement (TAS) involvement in guanosine metabolic process. DGUOK's substrate is 2'-deoxyguanosine, not guanosine (a ribonucleoside); the process term is slightly mis-specified. The accurate parent process is purine deoxyribonucleoside metabolism. Reason: DGUOK metabolises the deoxyribonucleoside deoxyguanosine, not the ribonucleoside guanosine; the term should be replaced by the deoxyribonucleoside-level process. Proposed replacements: purine deoxyribonucleoside metabolic process Supporting Evidence: PMID:8706825 phosphorylation of purine deoxyribonucleosides in the

Gene Description

Existing Annotations Review

Core Functions

Deoxyguanosine kinase activity: phosphorylates deoxyguanosine to dGMP in the mitochondrial matrix, using ATP as phosphate donor. This is the defining, rate-limiting purine-salvage activity of DGUOK.

Deoxyadenosine kinase activity: phosphorylates deoxyadenosine to dAMP (also deoxyinosine) in the mitochondrial matrix, the second purine substrate of the mitochondrial deoxyribonucleoside salvage pathway, feeding dAMP salvage.

References

📚 Additional Documentation

Notes

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