ak2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: mitochondrion (GO:0005739) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: Mitochondrion localization is true and a more specific intermembrane-space annotation is also present. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space file:DANRE/ak2/ak2-deep-research-falcon.md AK2 is repeatedly described as the adenylate kinase isozyme localized to the mitochondrial intermembrane space (IMS) and distinguished from AK3/AK4, which are generally described as mitochondrial matrix enzymes.
GO:0006172 ADP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: ADP biosynthetic process (GO:0006172) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: ADP biosynthesis directly reflects the AMP + ATP to ADP adenylate kinase reaction. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP; file:DANRE/ak2/ak2-deep-research-falcon.md A key functional framing is that AK2 generates ADP in the IMS, thereby helping supply ADP for mitochondrial ATP synthesis and coupling to adenine nucleotide exchange (e.g., via the adenine nucleotide translocator, ANT).
GO:0004017 AMP kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: AMP kinase activity (GO:0004017) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: AMP kinase/adenylate kinase activity is the core molecular function. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP; file:DANRE/ak2/ak2-uniprot.txt Catalyzes the reversible transfer of the terminal phosphate file:DANRE/ak2/ak2-deep-research-falcon.md For functional annotation of zebrafish Ak2 (Q1L8L9), the best-supported specific assignment from the available evidence remains adenylate kinase activity (EC 2.7.4.3) acting on ATP and AMP to produce ADP in the mitochondrial IMS.
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding (GO:0005524) is supported or plausible for zebrafish ak2, but it is not the most informative core function. Reason: ATP binding reflects substrate binding but is less informative than adenylate kinase activity. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0005758 mitochondrial intermembrane space	IEA GO_REF:0000120	ACCEPT	Summary: mitochondrial intermembrane space (GO:0005758) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: The mitochondrial intermembrane-space location is supported. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space PMID:26150473 AK2 is expressed in the mitochondrial intermembrane space file:DANRE/ak2/ak2-deep-research-falcon.md A review further emphasizes AK2 as the only AK isozyme in the IMS and links it to supplying ADP to ANT at the inner mitochondrial membrane.
GO:0006172 ADP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: ADP biosynthetic process (GO:0006172) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: ADP biosynthesis directly reflects the AMP + ATP to ADP adenylate kinase reaction. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0016776 phosphotransferase activity, phosphate group as acceptor	IEA GO_REF:0000002	MODIFY	Summary: phosphotransferase activity, phosphate group as acceptor (GO:0016776) captures the right general area for zebrafish ak2, but AMP kinase activity (GO:0004017) is the better supported term. Reason: The broad phosphotransferase annotation should be narrowed to AMP kinase/adenylate kinase activity. Proposed replacements: AMP kinase activity Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0019205 nucleobase-containing compound kinase activity	IEA GO_REF:0000002	MODIFY	Summary: nucleobase-containing compound kinase activity (GO:0019205) captures the right general area for zebrafish ak2, but AMP kinase activity (GO:0004017) is the better supported term. Reason: The generic nucleobase-containing compound kinase annotation should be narrowed to AMP kinase/adenylate kinase activity. Proposed replacements: AMP kinase activity Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0046033 AMP metabolic process	IEA GO_REF:0000104	ACCEPT	Summary: AMP metabolic process (GO:0046033) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: AMP metabolic process directly reflects AK2 substrate use. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0046034 ATP metabolic process	IEA GO_REF:0000104	ACCEPT	Summary: ATP metabolic process (GO:0046034) is supported for zebrafish ak2 and is coherent with the synthesized gene function. Reason: ATP metabolic process directly reflects AK2 substrate use. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP;
GO:0002244 hematopoietic progenitor cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: hematopoietic progenitor cell differentiation (GO:0002244) is supported or plausible for zebrafish ak2, but it is not the most informative core function. Reason: Hematopoietic progenitor cell differentiation is a developmental consequence of AK2 deficiency. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects in zebrafish file:DANRE/ak2/ak2-deep-research-falcon.md Across alleles and perturbations, ak2 deficiency impairs definitive hematopoiesis
GO:0060218 hematopoietic stem cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: hematopoietic stem cell differentiation (GO:0060218) is supported or plausible for zebrafish ak2, but it is not the most informative core function. Reason: Hematopoietic stem cell differentiation is a downstream developmental consequence of AK2 deficiency. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects in zebrafish file:DANRE/ak2/ak2-deep-research-falcon.md These findings support a mechanistic model in which AK2-mediated adenine nucleotide homeostasis in mitochondria protects hematopoietic development from ROS-associated stress.
GO:0002521 leukocyte differentiation	IMP PMID:19043417 Reticular dysgenesis (aleukocytosis) is caused by mutations ...	KEEP AS NON CORE	Summary: leukocyte differentiation (GO:0002521) is supported or plausible for zebrafish ak2, but it is not the most informative core function. Reason: Leukocyte differentiation is a well-supported phenotype of ak2 deficiency but not the core molecular function. Supporting Evidence: PMID:19043417 Knockdown of zebrafish ak2 also leads to aberrant leukocyte development
GO:0002244 hematopoietic progenitor cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate row for GO:0002244 recorded against an additional ak2 mutant/morphant reagent. ak2-null (ak2del2, ak2ins4) and L124P mutants, and translation/splice morphants, all show impaired myeloid, lymphoid and erythroid development. HSPC specification (c-myb/runx1 at 30-36 hpf) is largely normal, but c-myb collapses from 2-5 dpf, i.e. maturation/maintenance fails. The defect is driven by increased mitochondrial oxidative stress and apoptosis and is rescued by antioxidants, so ak2 acts through adenine-nucleotide/energy homeostasis rather than executing a differentiation step. Reason: Duplicate of the reviewed GO:0002244 row; same action for consistency across the ZFIN reagents. The gene product does not perform a step of hematopoietic differentiation; its adenylate kinase activity maintains the adenine nucleotide pool, and its loss causes ROS-mediated apoptosis that secondarily blocks HSPC maturation. Kept as non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish
GO:0002244 hematopoietic progenitor cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate row for GO:0002244 recorded against an additional ak2 mutant/morphant reagent. ak2-null (ak2del2, ak2ins4) and L124P mutants, and translation/splice morphants, all show impaired myeloid, lymphoid and erythroid development. HSPC specification (c-myb/runx1 at 30-36 hpf) is largely normal, but c-myb collapses from 2-5 dpf, i.e. maturation/maintenance fails. The defect is driven by increased mitochondrial oxidative stress and apoptosis and is rescued by antioxidants, so ak2 acts through adenine-nucleotide/energy homeostasis rather than executing a differentiation step. Reason: Duplicate of the reviewed GO:0002244 row; same action for consistency across the ZFIN reagents. The gene product does not perform a step of hematopoietic differentiation; its adenylate kinase activity maintains the adenine nucleotide pool, and its loss causes ROS-mediated apoptosis that secondarily blocks HSPC maturation. Kept as non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish
GO:0002244 hematopoietic progenitor cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate row for GO:0002244 recorded against an additional ak2 mutant/morphant reagent. ak2-null (ak2del2, ak2ins4) and L124P mutants, and translation/splice morphants, all show impaired myeloid, lymphoid and erythroid development. HSPC specification (c-myb/runx1 at 30-36 hpf) is largely normal, but c-myb collapses from 2-5 dpf, i.e. maturation/maintenance fails. The defect is driven by increased mitochondrial oxidative stress and apoptosis and is rescued by antioxidants, so ak2 acts through adenine-nucleotide/energy homeostasis rather than executing a differentiation step. Reason: Duplicate of the reviewed GO:0002244 row; same action for consistency across the ZFIN reagents. The gene product does not perform a step of hematopoietic differentiation; its adenylate kinase activity maintains the adenine nucleotide pool, and its loss causes ROS-mediated apoptosis that secondarily blocks HSPC maturation. Kept as non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish
GO:0004017 AMP kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT inference (node PTN000599576) of adenylate kinase / AMP kinase activity, the defining activity of the adenylate kinase family, seeded by experimentally characterised members across bacteria, yeast, fly, plant, rodent and human. Zebrafish ak2 retains the CORE/NMPbind/LID architecture and the ATP- and AMP-binding residues (UniProt features), and the L124P zebrafish disease allele in the CORE-LID hinge is predicted to impair activity. Reason: Core catalytic function; the activity arose at the root of the family and there is no evidence of loss or divergence in zebrafish ak2. Consistent with the IEA row and with the EC 2.7.4.3 / RHEA:12973 reaction on the UniProt entry. Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt Reaction=AMP + ATP = 2 ADP; file:DANRE/ak2/ak2-uniprot.txt Catalyzes the reversible transfer of the terminal phosphate
GO:0005737 cytoplasm	IBA GO_REF:0000033	MODIFY	Summary: PAINT inference (node PTN000599576) that adenylate kinase acts in the cytoplasm. The family node includes the cytosolic isozyme AK1 and its orthologs, so cytoplasm reflects the ancestral cytosolic localisation. The AK2 subfamily is targeted to the mitochondrial intermembrane space, which the zebrafish entry carries as a separate, more accurate annotation. Reason: The broad cytoplasmic location is true for the family generally but the AK2 subfamily has relocalised to the mitochondrial intermembrane space; the more specific GO:0005758 is supported by the UniProt subcellular-location line and by the existing IEA IMS annotation, so the cytoplasm term should be replaced by it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000599576 SUPPORTS SOURCE BUT NOT TARGET Family node covers cytosolic AK1-type members; cytoplasm is correct at the node but the AK2 subfamily is intermembrane-space localised. Proposed replacements: mitochondrial intermembrane space Supporting Evidence: file:DANRE/ak2/ak2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space
GO:0060218 hematopoietic stem cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate GO:0060218 row against an additional ak2 reagent. In ak2 mutants/morphants HSPC specification is preserved (near-normal c-myb/runx1 at 30-36 hpf) but the population is not maintained (c-myb reduced 2-5 dpf), with increased oxidative stress and apoptosis that antioxidant treatment rescues. Reason: Duplicate of the reviewed GO:0060218 row; same action for consistency. The phenotype shows AK2 energy metabolism is required for HSPC maturation/maintenance, not that the enzyme carries out stem-cell differentiation. Downstream metabolic requirement, kept non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish
GO:0060218 hematopoietic stem cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate GO:0060218 row against an additional ak2 reagent. In ak2 mutants/morphants HSPC specification is preserved (near-normal c-myb/runx1 at 30-36 hpf) but the population is not maintained (c-myb reduced 2-5 dpf), with increased oxidative stress and apoptosis that antioxidant treatment rescues. Reason: Duplicate of the reviewed GO:0060218 row; same action for consistency. The phenotype shows AK2 energy metabolism is required for HSPC maturation/maintenance, not that the enzyme carries out stem-cell differentiation. Downstream metabolic requirement, kept non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish
GO:0060218 hematopoietic stem cell differentiation	IMP PMID:26150473 Reticular dysgenesis-associated AK2 protects hematopoietic s...	KEEP AS NON CORE	Summary: ZFIN IMP (Rissone et al. 2015, full text available): a duplicate GO:0060218 row against an additional ak2 reagent. In ak2 mutants/morphants HSPC specification is preserved (near-normal c-myb/runx1 at 30-36 hpf) but the population is not maintained (c-myb reduced 2-5 dpf), with increased oxidative stress and apoptosis that antioxidant treatment rescues. Reason: Duplicate of the reviewed GO:0060218 row; same action for consistency. The phenotype shows AK2 energy metabolism is required for HSPC maturation/maintenance, not that the enzyme carries out stem-cell differentiation. Downstream metabolic requirement, kept non-core. Supporting Evidence: PMID:26150473 AK2 deficiency induces a wide array of hematopoietic defects PMID:26150473 Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish

Gene Description

Existing Annotations Review

Core Functions

ak2 enables mitochondrial adenylate kinase activity in the intermembrane space, reversibly converting AMP plus ATP to ADP and supporting ADP biosynthesis and adenine nucleotide metabolism.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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