ADK2

UniProt ID: P26364
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

ADK2 (AKY3/PAK3; YER170W) encodes the mitochondrial matrix GTP:AMP phosphotransferase of S. cerevisiae, the orthologue of vertebrate AK3. It catalyses NTP + AMP -> NDP + ADP using GTP or ITP but not ATP as phosphate donor. A strain-dependent frameshift near the 3' end yields a short (PAK3) or long (AKY3) C-terminus; both forms are active at 30 C, but the long form is more stable to heat and denaturation. Expression is low on glucose and rises on non-fermentable carbon sources. Disruption has no detectable phenotype, so its physiological role in mitochondrial nucleotide homeostasis (e.g. recycling AMP and GTP generated in the matrix) remains undefined.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004017 AMP kinase activity
IBA
GO_REF:0000033
REMOVE
Summary: IBA from PTN000599576, the adenylate kinase node that also covers ATP-using AK1/AK2 enzymes. Adk2 sits in the AK3 (GTP:AMP) subclade and has target-specific biochemical evidence that ATP is not a phosphate donor, so the ATP:AMP activity is lost/diverged in this lineage. The correct activity is captured by the IBA to nucleoside triphosphate adenylate kinase activity from the AK3 node.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000599576 SUPPORTS SOURCE BUT NOT TARGET
Node covers ATP-using AK1/AK2-type adenylate kinases; Adk2 belongs to the AK3 subclade (PTN008598552) that uses GTP/ITP and not ATP.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
IEA
GO_REF:0000002
REMOVE
Summary: IEA from InterPro IPR006259/IPR007862 (adenylate kinase family/lid domain) mapped to AMP kinase activity. The family signature does not discriminate the GTP-specific AK3 subfamily; biochemistry shows Adk2 does not use ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PWY-6126-1 (superpathway of adenosine nucleotides de novo biosynthesis II), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PWY-7219 (adenosine ribonucleotides de novo biosynthesis), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0004017 AMP kinase activity
RCA
GO_REF:0000123
REMOVE
Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways), where YeastCyc attaches Adk2 to the AMP + ATP <-> 2 ADP reaction alongside Adk1. This is a paralog over-assignment: Adk2 is a matrix GTP:AMP phosphotransferase that does not accept ATP.
Reason: Adk2 (yeast AK3 orthologue) uses GTP or ITP but does not accept ATP as phosphate donor, so ATP:AMP 'AMP kinase activity' is incorrect for this protein.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0005524 ATP binding
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: IEA from InterPro IPR000850/IPR006259 (adenylate kinase family), inferring ATP binding. Adk2 does not accept ATP as phosphate donor; its nucleotide donor site binds GTP/ITP. ATP binding is a family-level over-generalisation for this AK3 enzyme.
Reason: ATP is not a substrate of Adk2; the P-loop binds GTP/ITP.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0005737 cytoplasm
IBA
GO_REF:0000033
MODIFY
Summary: IBA (is_active_in cytoplasm) from PTN000599576, the broad adenylate kinase node dominated by cytosolic AK1/AK2 enzymes. Adk2 is located exclusively in the mitochondrial matrix; the matrix is technically within the cytoplasm in GO, but the IBA reflects cytosolic family members, not Adk2.
Reason: Adk2 is a mitochondrial matrix protein; cytoplasm (which in GO includes the mitochondria) is too general.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
PANTHER:PTN000599576 SUPPORTS SOURCE BUT NOT TARGET
Cytoplasmic activity is true of the AK1/AK2-type members of this node but not of the matrix-localised AK3-type Adk2.
Proposed replacements: mitochondrial matrix
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: HDA from the PROMITO mitochondrial proteome (Reinders et al. 2006). Correct.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were identified
PMID:8537371
was located exclusively in the mitochondrial matrix
GO:0005739 mitochondrion
IEA
GO_REF:0000002
ACCEPT
Summary: IEA from InterPro IPR028586 (AK3 mitochondrial). Correct.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005743 mitochondrial inner membrane
IDA
PMID:15753074
A GTP:AMP phosphotransferase, Adk2p, in Saccharomyces cerevi...
KEEP AS NON CORE
Summary: IDA (PMID:15753074) assigning Adk2 to the mitochondrial inner membrane. Both abstracts describe Adk2 as a matrix protein, so the inner-membrane annotation probably reflects a peripherally associated fraction in subfractionation. Abstract-only caches; defer to curator but treat as non-core.
Reason: Experimental but conflicts with the predominant matrix localisation; may reflect membrane-associated pool.
Supporting Evidence:
PMID:15753074
the corresponding protein exists as either Adk2p (short) or Adk2p (long) in the mitochondrial matrix
GO:0005743 mitochondrial inner membrane
IDA
PMID:8537371
Strain-dependent occurrence of functional GTP:AMP phosphotra...
KEEP AS NON CORE
Summary: IDA (PMID:8537371) assigning Adk2 to the mitochondrial inner membrane. Both abstracts describe Adk2 as a matrix protein, so the inner-membrane annotation probably reflects a peripherally associated fraction in subfractionation. Abstract-only caches; defer to curator but treat as non-core.
Reason: Experimental but conflicts with the predominant matrix localisation; may reflect membrane-associated pool.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
GO:0005759 mitochondrial matrix
IBA
GO_REF:0000033
ACCEPT
Summary: IBA (is_active_in) from PTN008598552 (AK3 clade). Correct; core location.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix
IDA
PMID:8537371
Strain-dependent occurrence of functional GTP:AMP phosphotra...
ACCEPT
Summary: IDA (Schricker et al. 1995): Adk2 protein was located exclusively in the mitochondrial matrix. Core location.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
GO:0005759 mitochondrial matrix
IDA
PMID:8537371
Strain-dependent occurrence of functional GTP:AMP phosphotra...
ACCEPT
Summary: IDA (Schricker et al. 1995): Adk2 protein was located exclusively in the mitochondrial matrix. Core location.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000120
ACCEPT
Summary: IEA from UniProt subcellular location SL-0170 / HAMAP MF_03169. Correct.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways PWY-6126-1 (superpathway of adenosine nucleotides de novo biosynthesis II), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways PWY-7219 (adenosine ribonucleotides de novo biosynthesis), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: RCA (is_active_in cytosol) from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways), which places all adenylate kinase reaction participants in the cytosol. Adk2 is exclusively mitochondrial (matrix).
Reason: Adk2 is a mitochondrial matrix protein; cytosol is inherited from a pathway built around Adk1.
Supporting Evidence:
PMID:8537371
was located exclusively in the mitochondrial matrix
file:yeast/ADK2/ADK2-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0006164 purine nucleotide biosynthetic process
RCA
GO_REF:0000123
MARK AS OVER ANNOTATED
Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), which attaches Adk2 to the cytosolic ATP:AMP step. Adk2 is a matrix GTP:AMP phosphotransferase whose loss has no phenotype; there is no evidence that it contributes to purine nucleotide biosynthesis.
Reason: Adk2 is dispensable and acts on GTP:AMP in the matrix, not in de novo purine synthesis.
Supporting Evidence:
PMID:8537371
yeast mitochondria can completely dispense with GTP:AMP phosphotransferase activity
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0006164 purine nucleotide biosynthetic process
RCA
GO_REF:0000123
MARK AS OVER ANNOTATED
Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), which attaches Adk2 to the cytosolic ATP:AMP step. Adk2 is a matrix GTP:AMP phosphotransferase whose loss has no phenotype; there is no evidence that it contributes to purine nucleotide biosynthesis.
Reason: Adk2 is dispensable and acts on GTP:AMP in the matrix, not in de novo purine synthesis.
Supporting Evidence:
PMID:8537371
yeast mitochondria can completely dispense with GTP:AMP phosphotransferase activity
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0006172 ADP biosynthetic process
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: IEA from HAMAP MF_03169. ADP is a direct product of the GTP:AMP phosphotransferase reaction, so the term is chemically correct, though the physiological importance is unclear (null has no phenotype).
Reason: Correct product-level BP, but the enzyme is dispensable.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
PMID:8537371
disruption of the AKY3 allele displayed no phenotype
GO:0009117 nucleotide metabolic process
IDA
PMID:15753074
A GTP:AMP phosphotransferase, Adk2p, in Saccharomyces cerevi...
ACCEPT
Summary: IDA (Gu et al. 2005): Adk2 is an active nucleoside phosphate interconverting enzyme. Correct general BP.
Supporting Evidence:
PMID:15753074
Adenylate kinases participate in maintaining the homeostasis of cellular nucleotides
PMID:15753074
both short and long forms of Adk2p are enzymatically active
GO:0009117 nucleotide metabolic process
IEA
GO_REF:0000117
ACCEPT
Summary: IEA from ARBA00027584. Correct general BP.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities. Does not accept ATP as phosphate donor.
GO:0009142 nucleoside triphosphate biosynthetic process
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: IBA from PTN008598552 (AK3 clade). The GTP:AMP phosphotransferase reaction converts GTP + AMP to GDP + ADP, i.e. consumes rather than synthesises a nucleoside triphosphate. Any NTP formation would be via other enzymes regenerating GTP/ATP from the products.
Reason: The reaction consumes an NTP; it does not synthesise one.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: ROLE CONFLATION
Sources checked:
PANTHER:PTN008598552 SOURCE WEAK OR INFERRED
The AK3 node correctly carries GTP:AMP phosphotransferase activity, but NTP biosynthesis conflates the NTP-consuming reaction with NTP synthesis.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
GO:0009165 nucleotide biosynthetic process
RCA
GO_REF:0000123
MARK AS OVER ANNOTATED
Summary: RCA from YeastPathways superpathway PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis) via the ATP:AMP reaction Adk2 does not catalyse. Not supported for Adk2.
Reason: Inherited from a superpathway via the wrong (ATP:AMP) reaction.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
PMID:8537371
yeast mitochondria can completely dispense with GTP:AMP phosphotransferase activity
GO:0016776 phosphotransferase activity, phosphate group as acceptor
IEA
GO_REF:0000120
TOO GENERAL
Summary: IEA from ARBA00026253 / InterPro IPR006259. Correct parent of nucleoside triphosphate adenylate kinase activity, uninformative.
Reason: Uninformative parent of the core MF.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
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 the core MF.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
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). Adk2 is a dispensable matrix GTP:AMP phosphotransferase; no evidence for a role in purine salvage.
Reason: Inherited from a biosynthesis+salvage superpathway via the wrong reaction.
Supporting Evidence:
PMID:8537371
yeast mitochondria can completely dispense with GTP:AMP phosphotransferase activity
GO:0046033 AMP metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN008598552 (AK3 clade). AMP is the phosphate acceptor of Adk2; correct and the most appropriate BP for this enzyme.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
GO:0046033 AMP metabolic process
IEA
GO_REF:0000104
ACCEPT
Summary: IEA from HAMAP MF_03169. Correct.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
GO:0046039 GTP metabolic process
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: IEA from HAMAP MF_03169 (GTP metabolic process). Adk2 uses GTP as phosphate donor (GTP:AMP and ITP:AMP activities), so it participates in GTP metabolism; correct but secondary.
Reason: GTP is a phosphate donor of Adk2; correct but secondary.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0046041 ITP metabolic process
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: IEA from HAMAP MF_03169 (ITP metabolic process). Adk2 uses ITP as phosphate donor (GTP:AMP and ITP:AMP activities), so it participates in ITP metabolism; correct but secondary.
Reason: ITP is a phosphate donor of Adk2; correct but secondary.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
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' was mapped to the nucleoside term 'adenosine biosynthetic process'. Adk2 does not synthesise adenosine.
Reason: Adenosine is a nucleoside; Adk2 neither makes nor uses it, and the ATP:AMP reaction behind the row is not an Adk2 activity.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
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' was mapped to the nucleoside term 'adenosine biosynthetic process'. Adk2 does not synthesise adenosine.
Reason: Adenosine is a nucleoside; Adk2 neither makes nor uses it, and the ATP:AMP reaction behind the row is not an Adk2 activity.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0046899 nucleoside triphosphate adenylate kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN008598552 (AK3 clade, GTP:AMP phosphotransferase). Correct; core MF.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
file:yeast/ADK2/ADK2-uniprot.txt
Belongs to the adenylate kinase family. AK3 subfamily.
GO:0046899 nucleoside triphosphate adenylate kinase activity
IDA
PMID:15753074
A GTP:AMP phosphotransferase, Adk2p, in Saccharomyces cerevi...
ACCEPT
Summary: IDA (Gu et al. 2005): purified short and long forms of Adk2 are both enzymatically active GTP:AMP phosphotransferases at 30 C. Core MF.
Supporting Evidence:
PMID:15753074
both short and long forms of Adk2p are enzymatically active
GO:0046899 nucleoside triphosphate adenylate kinase activity
IDA
PMID:8537371
Strain-dependent occurrence of functional GTP:AMP phosphotra...
ACCEPT
Summary: IDA (Schricker et al. 1995): the active AKY3 allele product showed GTP:AMP and ITP:AMP phosphotransferase activity but did not use ATP. Core MF.
Supporting Evidence:
PMID:8537371
The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
GO:0046899 nucleoside triphosphate adenylate kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: IEA via RHEA:13749 / EC 2.7.4.10 and HAMAP MF_03169. Correct.
Supporting Evidence:
file:yeast/ADK2/ADK2-uniprot.txt
Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-

Core Functions

Mitochondrial matrix GTP/ITP:AMP phosphotransferase (AK3-type) that converts AMP to ADP using GTP or ITP, not ATP.

Supporting Evidence:
  • PMID:8537371
    The encoded protein exhibited GTP:AMP and ITP:AMP phosphotransferase activities but did not accept ATP as phosphate donor
  • PMID:8537371
    was located exclusively in the mitochondrial matrix
  • PMID:15753074
    both short and long forms of Adk2p are enzymatically active
  • file:yeast/ADK2/ADK2-uniprot.txt
    Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-

References

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Suggested Questions for Experts

Q: What is the physiological role of the matrix GTP:AMP phosphotransferase, given that its loss has no phenotype (e.g. recycling AMP from matrix acyl-CoA synthetases using succinyl-CoA synthetase-derived GTP)?

Q: Is the inner-membrane association of Adk2 functionally significant or a fractionation artefact?

Suggested Experiments

Experiment: Measure matrix AMP/GTP/GDP pools and acyl-CoA synthetase-dependent processes (e.g. lipoylation, mtFAS) in adk2 null cells under respiratory growth and heat stress.

Deep Research

SGD

(ADK2-deep-research-sgd.md)
SGD gene description for ADK2 (yeast) SGD

SGD gene description for ADK2 (yeast)

Mitochondrial adenylate kinase; catalyzes the reversible synthesis of GTP and AMP from GDP and ADP; may serve as a back-up for synthesizing GTP or ADP depending on metabolic conditions; 3' sequence of ADK2 varies with strain background

πŸ“š Additional Documentation

Notes

(ADK2-notes.md)

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