ADK1

UniProt ID: P07170
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

ADK1 (AKY2; YDR226W) encodes the major adenylate kinase of S. cerevisiae (AK2 subfamily), which catalyses the reversible reaction AMP + ATP <-> 2 ADP. About 90% of the protein is cytosolic and ~10% is imported, without a cleavable presequence, into the mitochondrial intermembrane space. Adk1 maintains adenine nucleotide homeostasis and energy charge; adk1 null mutants are viable but slow-growing, respiration-deficient and temperature-sensitive, retaining ~10% of cytosolic activity from a minor, exclusively cytoplasmic isozyme. Loss of Adk1 catalytic activity changes adenylate pools and derepresses the PHO and ADE regulons. Adk1 has also been reported to associate with chromatin and Orc3 and to promote pre-replicative complex assembly.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003688 DNA replication origin binding
IDA
PMID:20659900
ATP-dependent pre-replicative complex assembly is facilitate...
MARK AS OVER ANNOTATED
Summary: IDA (Cheng et al. 2010): Adk1 was detected at replication origins by ChIP and binds chromatin/Orc3. ChIP shows proximity to origins, most plausibly via ORC, rather than direct sequence-specific binding to origin DNA by a cytosolic/IMS adenylate kinase. The moonlighting replication role is captured as non-core by the pre-RC assembly row.
Reason: ChIP association with origins does not demonstrate sequence-specific origin DNA binding.
Supporting Evidence:
PMID:20659900
Adk1p associated with replication origins by ChIP assay
PMID:20659900
Adk1p bound to chromatin throughout the cell cycle and physically interacted with Orc3p
GO:0004017 AMP kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PANTHER node PTN000599576 (adenylate kinase). Adk1 is the major ATP:AMP adenylate kinase (AK2 subfamily) of yeast; core MF.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Belongs to the adenylate kinase family. AK2 subfamily.
GO:0004017 AMP kinase activity
IDA
PMID:15753074
A GTP:AMP phosphotransferase, Adk2p, in Saccharomyces cerevi...
ACCEPT
Summary: IDA (Gu et al. 2005): a study of the paralog Adk2 that also characterised adenylate kinase activities; abstract-only cache does not show the Adk1 assay, so defer to the curator. Adk1 ATP:AMP activity is independently well established.
Supporting Evidence:
PMID:15753074
Adenylate kinases participate in maintaining the homeostasis of cellular nucleotides
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0004017 AMP kinase activity
IDA
PMID:18433446
Co-regulation of yeast purine and phosphate pathways in resp...
ACCEPT
Summary: IDA (Gauthier et al. 2008): adk1 point mutants isolated for PHO5 misregulation all severely reduced Adk1 catalytic activity, and catalytic activity was critical for PHO/ADE regulation. Core MF.
Supporting Evidence:
PMID:18433446
these mutations also severely affected Adk1p catalytic activity
PMID:18433446
adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways
GO:0004017 AMP kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: IEA via RHEA:12973 / EC 2.7.4.3 and HAMAP MF_03168. Correct for Adk1.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0004017 AMP kinase activity
IMP
PMID:18433446
Co-regulation of yeast purine and phosphate pathways in resp...
ACCEPT
Summary: IMP (Gauthier et al. 2008): loss-of-function adk1 alleles lose catalytic activity and are rescued by heterologous adenylate kinase. Core MF.
Supporting Evidence:
PMID:18433446
these mutations also severely affected Adk1p catalytic activity
PMID:18433446
adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways
GO:0004017 AMP kinase activity
IMP
PMID:2850178
Yeast adenylate kinase is active simultaneously in mitochond...
ACCEPT
Summary: IMP (Bandlow et al. 1988): disruption of ADK1 abolishes mitochondrial adenylate kinase activity and removes ~90% of cytoplasmic activity. Core MF.
Supporting Evidence:
PMID:2850178
Adenylate kinase activity is found both in mitochondria and cytoplasm of wild type yeast
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways PWY-6126-1 (superpathway of adenosine nucleotides de novo biosynthesis II), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways PWY-7219 (adenosine ribonucleotides de novo biosynthesis), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways), assigning Adk1 to AMP + ATP <-> 2 ADP (EC 2.7.4.3). Correct reaction for Adk1, which supplies ADP from AMP made by the de novo and salvage pathways.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0005524 ATP binding
IDA
PMID:7635152
Stability, activity and structure of adenylate kinase mutant...
KEEP AS NON CORE
Summary: IDA from structural/biochemical work on yeast adenylate kinase (PMID:7635152) showing ATP (or ATP-analogue/Ap5A) bound in the LID/CORE site. Correct, but ATP binding is part of the catalytic AMP kinase activity rather than a separate function.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
PMID:7635152
Sequence/structure relationships have been explored by site-directed mutagenesis using a structurally known adenylate kinase
GO:0005524 ATP binding
IDA
PMID:7670369
High-resolution structures of adenylate kinase from yeast li...
KEEP AS NON CORE
Summary: IDA from structural/biochemical work on yeast adenylate kinase (PMID:7670369) showing ATP (or ATP-analogue/Ap5A) bound in the LID/CORE site. Correct, but ATP binding is part of the catalytic AMP kinase activity rather than a separate function.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
PMID:7670369
The structure of adenylate kinase from yeast ligated with the two-substrate-mimicking inhibitor Ap5A and Mg2+ has been refined to 1.96 A resolution
GO:0005524 ATP binding
IDA
PMID:8594191
Structure of a mutant adenylate kinase ligated with an ATP-a...
KEEP AS NON CORE
Summary: IDA from structural/biochemical work on yeast adenylate kinase (PMID:8594191) showing ATP (or ATP-analogue/Ap5A) bound in the LID/CORE site. Correct, but ATP binding is part of the catalytic AMP kinase activity rather than a separate function.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
PMID:8594191
two domains, LID and NMPbind, close over the bound substrates, ATP and AMP, respectively
GO:0005524 ATP binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA from InterPro IPR000850/IPR006259 (adenylate kinase). ATP is a substrate; true but subsumed by AMP kinase activity.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0005737 cytoplasm
IBA
GO_REF:0000033
ACCEPT
Summary: IBA (is_active_in cytoplasm) from PTN000599576. Correct; Adk1 is ~90% cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
GO:0005737 cytoplasm
IDA
PMID:2850178
Yeast adenylate kinase is active simultaneously in mitochond...
ACCEPT
Summary: IDA (Bandlow et al. 1988): adenylate kinase protein and activity detected in the cytoplasmic fraction. Correct; cytosol is the more specific term.
Supporting Evidence:
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005737 cytoplasm
IEA
GO_REF:0000104
ACCEPT
Summary: IEA from HAMAP MF_03168. Correct.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: HDA mitochondrial proteomics (PMID:16823961) detecting Adk1. Correct; the mitochondrial pool is in the intermembrane space.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were identified
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph...
ACCEPT
Summary: HDA mitochondrial proteomics (PMID:24769239) detecting Adk1. Correct; the mitochondrial pool is in the intermembrane space.
Supporting Evidence:
PMID:24769239
quantitative proteomic and phosphoproteomic study of isolated mitochondria
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: IBA (is_active_in mitochondrion) from PTN001916109 (AK2 clade, whose members are IMS enzymes). Correct; Adk1 is partly in the mitochondrial intermembrane space.
Supporting Evidence:
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
file:yeast/ADK1/ADK1-uniprot.txt
Belongs to the adenylate kinase family. AK2 subfamily.
GO:0005758 mitochondrial intermembrane space
EXP
PMID:12045196
Redundant mitochondrial targeting signals in yeast adenylate...
ACCEPT
Summary: EXP (PMID:12045196) placing Adk1 in the mitochondrial intermembrane space (protease protection/submitochondrial fractionation, IMS proteomics). Adk1 is imported without a cleavable presequence and sorted to the IMS, where it equilibrates adenine nucleotides exchanged by the ADP/ATP carrier. Core location.
Supporting Evidence:
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005758 mitochondrial intermembrane space
EXP
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: EXP (PMID:16823961) placing Adk1 in the mitochondrial intermembrane space (protease protection/submitochondrial fractionation, IMS proteomics). Adk1 is imported without a cleavable presequence and sorted to the IMS, where it equilibrates adenine nucleotides exchanged by the ADP/ATP carrier. Core location.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were identified
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005758 mitochondrial intermembrane space
EXP
PMID:22984289
Intermembrane space proteome of yeast mitochondria.
ACCEPT
Summary: EXP (PMID:22984289) placing Adk1 in the mitochondrial intermembrane space (protease protection/submitochondrial fractionation, IMS proteomics). Adk1 is imported without a cleavable presequence and sorted to the IMS, where it equilibrates adenine nucleotides exchanged by the ADP/ATP carrier. Core location.
Supporting Evidence:
PMID:22984289
many of the known IMS proteins either were localized to the cytosol and/or the nucleus
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005758 mitochondrial intermembrane space
IDA
PMID:2850178
Yeast adenylate kinase is active simultaneously in mitochond...
ACCEPT
Summary: IDA (PMID:2850178) placing Adk1 in the mitochondrial intermembrane space (protease protection/submitochondrial fractionation, IMS proteomics). Adk1 is imported without a cleavable presequence and sorted to the IMS, where it equilibrates adenine nucleotides exchanged by the ADP/ATP carrier. Core location.
Supporting Evidence:
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005758 mitochondrial intermembrane space
IEA
GO_REF:0000120
ACCEPT
Summary: IEA from UniProt subcellular location SL-0169 / HAMAP. Correct.
Supporting Evidence:
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005829 cytosol
IDA
PMID:12045196
Redundant mitochondrial targeting signals in yeast adenylate...
ACCEPT
Summary: IDA (PMID:12045196): fractionation shows Adk1 in the cytosol as well as mitochondria. Core location.
Supporting Evidence:
PMID:12045196
Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
GO:0005829 cytosol
IDA
PMID:2850178
Yeast adenylate kinase is active simultaneously in mitochond...
ACCEPT
Summary: IDA (PMID:2850178): fractionation shows Adk1 in the cytosol as well as mitochondria. Core location.
Supporting Evidence:
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
IEA
GO_REF:0000044
ACCEPT
Summary: IEA from UniProt subcellular location SL-0091 (Cytoplasm, cytosol). Correct.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways PWY-6126-1 (superpathway of adenosine nucleotides de novo biosynthesis II). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways PWY-7219 (adenosine ribonucleotides de novo biosynthesis). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA (is_active_in cytosol) from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). Correct: ~90% of Adk1 is cytosolic.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Note=90% cytoplasmic, 10% mitochondrial.
PMID:2850178
yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
GO:0006164 purine nucleotide biosynthetic process
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). Adenylate kinase converts de novo AMP to ADP en route to ATP, so participation in purine nucleotide biosynthesis is reasonable; ADP biosynthetic process is the precise term.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
PMID:18433446
adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways
GO:0006164 purine nucleotide biosynthetic process
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). Adenylate kinase converts de novo AMP to ADP en route to ATP, so participation in purine nucleotide biosynthesis is reasonable; ADP biosynthetic process is the precise term.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
PMID:18433446
adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways
GO:0006172 ADP biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000599693. ADP formation is the direct product of the AMP kinase reaction. Core BP.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0006172 ADP biosynthetic process
IDA
PMID:2848829
Analysis and in vivo disruption of the gene coding for adeny...
ACCEPT
Summary: IDA (Konrad 1988): ADK1 encodes the major adenylate kinase; disruption leaves only ~10% activity and lowers nucleoside triphosphate levels. ADP formation from AMP + ATP is the direct product of the reaction. Core BP.
Supporting Evidence:
PMID:2848829
the ADK1 gene is needed for normal cell proliferation but is not essential for cell viability
PMID:2848829
a significant decrease in the level of nucleoside triphosphates was found in the mutant strain
GO:0006172 ADP biosynthetic process
IEA
GO_REF:0000120
ACCEPT
Summary: IEA from InterPro IPR028587 / HAMAP. Correct.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0006270 DNA replication initiation
IMP
PMID:20980819
Identification of novel factors involved in or regulating in...
KEEP AS NON CORE
Summary: IMP (Ma et al. 2010): a genome-wide plasmid-loss screen recovered adk1 among mutants defective in single-origin plasmid maintenance. Supports a role in replication initiation (elaborated in Cheng et al. 2010), but this is a secondary, mechanistically unresolved role.
Reason: Moonlighting role from a single lab; not the core metabolic function.
Supporting Evidence:
PMID:20980819
identified several novel factors, including Ctf1p Ctf3p, Ctf4p, Ctf18p, Adk1p and Cdc60p
GO:0009117 nucleotide metabolic process
IEA
GO_REF:0000117
TOO GENERAL
Summary: IEA from ARBA00027584. True but general.
Reason: Correct but general parent.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0009117 nucleotide metabolic process
IMP
PMID:2850178
Yeast adenylate kinase is active simultaneously in mitochond...
TOO GENERAL
Summary: IMP (Bandlow et al. 1988): adk1 disruptants are petite-like and grow slowly. True but general; ADP biosynthesis/AMP metabolism are more specific.
Reason: Correct but general parent.
Supporting Evidence:
PMID:2850178
The phenotype of these disruption mutants is pet
GO:0009165 nucleotide biosynthetic process
RCA
GO_REF:0000123
TOO GENERAL
Summary: RCA from YeastPathways superpathway PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). True in a broad sense (ADP for ATP regeneration) but uninformative.
Reason: True but very general parent from a superpathway.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0016208 AMP binding
IDA
PMID:7635152
Stability, activity and structure of adenylate kinase mutant...
KEEP AS NON CORE
Summary: IDA from yeast adenylate kinase structures (PMID:7635152) with AMP (or Ap5A, which occupies both ATP and AMP sites) in the NMPbind site. Correct but subsumed by AMP kinase activity.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
PMID:7635152
Sequence/structure relationships have been explored by site-directed mutagenesis using a structurally known adenylate kinase
GO:0016208 AMP binding
IDA
PMID:7670369
High-resolution structures of adenylate kinase from yeast li...
KEEP AS NON CORE
Summary: IDA from yeast adenylate kinase structures (PMID:7670369) with AMP (or Ap5A, which occupies both ATP and AMP sites) in the NMPbind site. Correct but subsumed by AMP kinase activity.
Reason: Substrate binding implied by the catalytic MF.
Supporting Evidence:
PMID:7670369
The structure of adenylate kinase from yeast ligated with the two-substrate-mimicking inhibitor Ap5A and Mg2+ has been refined to 1.96 A resolution
GO:0016776 phosphotransferase activity, phosphate group as acceptor
IEA
GO_REF:0000120
TOO GENERAL
Summary: IEA from ARBA00026253 / InterPro IPR006259. Correct parent of AMP kinase activity, uninformative.
Reason: Uninformative parent of AMP kinase activity.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0019205 nucleobase-containing compound kinase activity
IEA
GO_REF:0000120
TOO GENERAL
Summary: IEA from ARBA00028083 / InterPro IPR000850. Correct parent, uninformative.
Reason: Uninformative parent of AMP kinase activity.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0036388 pre-replicative complex assembly
IMP
PMID:20659900
ATP-dependent pre-replicative complex assembly is facilitate...
KEEP AS NON CORE
Summary: IMP (Cheng et al. 2010): depletion of Adk1 (adk1-td) prevented pre-RC assembly, and the adk1(G20S) P-loop mutant was defective in replication initiation and Orc3 binding without changing cellular ATP. Accept as a non-core role.
Reason: Moonlighting role from a single study; mechanism (local ATP supply to ORC/Cdc6 vs structural) unresolved.
Supporting Evidence:
PMID:20659900
Adk1-td protein depletion prevented pre-RC assembly during the M-to-G(1) transition
PMID:20659900
Adk1p bound to chromatin throughout the cell cycle and physically interacted with Orc3p
GO:0043101 purine-containing compound salvage
RCA
GO_REF:0000123
MARK AS OVER ANNOTATED
Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). Adk1 phosphorylates AMP whatever its origin (de novo, Apt1 salvage, or ATP-consuming reactions); it is a general adenine-nucleotide interconversion enzyme rather than a step of base/nucleoside salvage.
Reason: Inherited from a biosynthesis+salvage superpathway; Adk1 phosphorylates AMP irrespective of its source.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0046033 AMP metabolic process
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: IEA from HAMAP MF_03168 (AMP metabolic process). Adk1 interconverts AMP, ADP and ATP and buffers the adenylate energy charge; true but less specific than ADP biosynthetic process.
Reason: Correct but general metabolic-process term.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0046034 ATP metabolic process
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: IEA from HAMAP MF_03168 (ATP metabolic process). Adk1 interconverts AMP, ADP and ATP and buffers the adenylate energy charge; true but less specific than ADP biosynthetic process.
Reason: Correct but general metabolic-process term.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP
GO:0046086 adenosine biosynthetic process
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PWY-6126-1 (superpathway of adenosine nucleotides de novo biosynthesis II). The pathway name 'adenosine ribonucleotides de novo biosynthesis' has been mapped to the nucleoside term 'adenosine biosynthetic process'. Adk1 converts AMP + ATP to 2 ADP; it does not synthesise adenosine. Mapping error.
Reason: Adenosine is a nucleoside; adenylate kinase neither makes nor uses it.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP
GO:0046086 adenosine biosynthetic process
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PWY-7219 (adenosine ribonucleotides de novo biosynthesis). The pathway name 'adenosine ribonucleotides de novo biosynthesis' has been mapped to the nucleoside term 'adenosine biosynthetic process'. Adk1 converts AMP + ATP to 2 ADP; it does not synthesise adenosine. Mapping error.
Reason: Adenosine is a nucleoside; adenylate kinase neither makes nor uses it.
Supporting Evidence:
file:yeast/ADK1/ADK1-uniprot.txt
Reaction=AMP + ATP = 2 ADP

Core Functions

ATP:AMP phosphotransferase (adenylate kinase) interconverting AMP, ADP and ATP in the cytosol and mitochondrial intermembrane space.

Supporting Evidence:
  • file:yeast/ADK1/ADK1-uniprot.txt
    Reaction=AMP + ATP = 2 ADP
  • PMID:2850178
    Adenylate kinase activity is found both in mitochondria and cytoplasm of wild type yeast
  • PMID:2850178
    yeast adenylate kinase (long version, AKY2) simultaneously occurs and is active in mitochondria and cytoplasm of the wild type
  • PMID:12045196
    Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space
  • PMID:18433446
    adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways

References

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Suggested Questions for Experts

Q: Is the pre-RC assembly role of Adk1 catalytic (local ADP/ATP buffering for ORC/Cdc6 ATPases) or structural (Orc3 binding)?

Q: Which enzyme supplies the residual ~10% cytosolic adenylate kinase activity in adk1 null cells?

Suggested Experiments

Experiment: Test whether catalytically dead but Orc3-binding-competent Adk1 variants support pre-RC assembly, separating catalytic from scaffolding roles.

Deep Research

SGD

(ADK1-deep-research-sgd.md)
SGD gene description for ADK1 (yeast) SGD

SGD gene description for ADK1 (yeast)

Adenylate kinase, required for purine metabolism; controls ATP homeostasis; localized to the cytoplasm and the mitochondria; lacks cleavable signal sequence; protein abundance increases in response to DNA replication stress; mutations affecting Adk1p catalytic activity deregulate expression of phosphate utilization genes PHO5 and PHO84; human homolog AK1 can complement yeast adk1 mutant

πŸ“š Additional Documentation

Notes

(ADK1-notes.md)

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πŸ“„ View Raw YAML

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