{"gene":"PF3D7_0816900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2008,"finding":"Recombinantly produced AK2 (PF3D7_0816900) is a monomeric protein of 33 kDa with adenylate kinase enzymatic activity (specific activity of 10 U/mg with ATP and AMP as substrate pair) and is inhibited by P1,P5-(diadenosine-5')-pentaphosphate (IC50=200 nM). AK2 is N-myristoylated by P. falciparum N-myristoyltransferase (NMT), as demonstrated by co-expression in E. coli and mass spectrometry; myristoylation significantly enhances AK2 stability. Furthermore, AK2 and NMT form a heterodimeric complex in vitro.","method":"Recombinant protein production, in vitro enzymatic assay, co-expression in E. coli, protein purification, mass spectrometry","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with substrate characterization, myristoylation confirmed by mass spectrometry, heterodimer formation directly demonstrated; single lab but multiple orthogonal methods","pmids":["18973776"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Using GFP-fusion proteins and live cell imaging, AK2 (PF3D7_0816900) was localized to the parasitophorous vacuole membrane (PVM) in P. falciparum, and this localization is driven by N-myristoylation.","method":"GFP-fusion protein expression, live cell fluorescence microscopy","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by live imaging with GFP fusions, single lab, replicated finding consistent with prior biochemical data","pmids":["22819813"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Biochemical and microscopy analyses of AK2 (PF3D7_0816900) GFP-tagged variants showed that three N-terminal motifs — N-myristoylation, a cysteine potential S-palmitoylation site, and a stretch of basic (lysine) residues — are collectively involved in targeting AK2 to the parasite plasma membrane (PPM) and its translocation across the PPM into the parasitophorous vacuole (PV). The N-terminal 37 amino acids of AK2 alone are sufficient to target and translocate GFP across the PPM.","method":"GFP-tagged variant expression, biochemical fractionation, fluorescence microscopy, chimeric fusion protein analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple GFP variants and chimeric proteins analyzed, combined biochemical and imaging approaches, single lab","pmids":["25909331"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Co-expression and confocal microscopy showed that AK2 (PF3D7_0816900) and PfRab5b are co-transported from a compartment near the endoplasmic reticulum to the tubovesicular network (TVN) via an N-myristoylation-dependent, non-classical membrane-trafficking pathway. Overexpression of PfRab5b abrogated transport of AK2 to the PVM and caused AK2 accumulation in punctate structures together with PfRab5b.","method":"Co-expression with destabilization-domain (DD)-tagged PfRab5b, selective membrane permeabilization, confocal microscopy","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic and imaging approaches including selective permeabilization and overexpression phenotype; single lab","pmids":["27316546"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Genetic expression of active or inactive PfArf1 mutants specifically inhibited trafficking of AK2 (PF3D7_0816900) to the PVM, establishing that PfArf1 GTPase sorts AK2 at the ER into the PV-directed pathway. PfRab1b mutants did not affect AK2 transport. This defines the pathway as: AK2 is recognized at an ER subdomain by PfArf1 and directed toward the PV independently of the PEXEL export pathway.","method":"Co-immunoprecipitation with mass spectrometry to identify PfRab5b-associated proteins, expression of constitutively active/inactive GTPase mutants, indirect immunofluorescence assay, super-resolution microscopy","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via active/inactive mutants combined with co-IP/MS and super-resolution imaging; single lab, multiple orthogonal methods","pmids":["33604307"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum AK2 (PF3D7_0816900) is a monomeric 33 kDa adenylate kinase that catalyzes ATP+AMP↔2 ADP; its N-terminus carries a myristoylation signal (modified by PfNMT, which also forms a heterodimer with AK2), a palmitoylation site, and a basic lysine cluster that together drive targeting to the parasite plasma membrane and translocation across it into the parasitophorous vacuole, with final delivery to the PVM/tubovesicular network regulated by PfArf1-mediated sorting from the ER via an N-myristoylation-dependent, PEXEL-independent trafficking pathway."},"narrative":{"mechanistic_narrative":"AK2 (PF3D7_0816900) is a monomeric 33 kDa adenylate kinase of Plasmodium falciparum that catalyzes the interconversion of ATP and AMP to ADP and is inhibited by P1,P5-(diadenosine-5')-pentaphosphate [PMID:18973776]. Its N-terminus is N-myristoylated by P. falciparum N-myristoyltransferase (with which AK2 forms a heterodimer in vitro), a modification that stabilizes the enzyme [PMID:18973776], and together with a potential S-palmitoylation cysteine and a basic lysine cluster constitutes a targeting module: the N-terminal 37 residues alone are sufficient to direct AK2 to the parasite plasma membrane and drive its translocation across it into the parasitophorous vacuole [PMID:25909331]. Downstream of the plasma membrane, AK2 is delivered to the parasitophorous vacuole membrane and tubovesicular network by an N-myristoylation-dependent, PEXEL-independent trafficking route: it is sorted at an ER subdomain by the PfArf1 GTPase toward the PV [PMID:33604307] and co-transported with PfRab5b to the tubovesicular network, with PfRab5b overexpression rerouting AK2 into punctate structures and blocking its arrival at the PVM [PMID:27316546, PMID:22819813]. The physiological consequence of AK2 enzymatic activity at these membranes has not been characterized in the available corpus.","teleology":[{"year":2008,"claim":"Establishing that PF3D7_0816900 is a bona fide, monomeric adenylate kinase whose N-terminus is myristoylated by parasite NMT answered whether the protein is enzymatically active and post-translationally lipidated.","evidence":"Recombinant protein production, in vitro adenylate kinase assay with inhibitor characterization, co-expression with NMT in E. coli, mass spectrometry","pmids":["18973776"],"confidence":"High","gaps":["Physiological substrate flux and role of AK2 activity in parasite energy metabolism not addressed","Functional significance of the AK2–NMT heterodimer in vivo unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Localizing AK2 to the parasitophorous vacuole membrane and linking that localization to N-myristoylation answered where the enzyme resides and implicated its lipid modification in targeting.","evidence":"GFP-fusion protein expression and live cell fluorescence microscopy","pmids":["22819813"],"confidence":"Medium","gaps":["Mechanism connecting myristoylation to PVM delivery not resolved at this stage","Single-lab GFP-fusion result without endogenous tag validation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Dissecting the N-terminal targeting elements answered how AK2 is directed to and translocated across the plasma membrane, identifying a three-motif code.","evidence":"GFP-tagged variants and chimeric fusions, biochemical fractionation, fluorescence microscopy","pmids":["25909331"],"confidence":"Medium","gaps":["Machinery that recognizes the palmitoylation and lysine motifs not identified","Mechanism of translocation across the plasma membrane not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Demonstrating co-transport with PfRab5b from an ER-proximal compartment to the tubovesicular network answered which trafficking route carries AK2 beyond the plasma membrane.","evidence":"Co-expression with DD-tagged PfRab5b, selective membrane permeabilization, confocal microscopy, PfRab5b overexpression phenotype","pmids":["27316546"],"confidence":"Medium","gaps":["Whether PfRab5b directly binds AK2 or acts indirectly not established","Cargo-recognition step at the ER not defined at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Identifying PfArf1 as the GTPase that sorts AK2 at the ER answered how AK2 enters the PV-directed, PEXEL-independent pathway and distinguished it from PfRab1b-dependent routes.","evidence":"Co-IP/MS of PfRab5b-associated proteins, constitutively active/inactive GTPase mutants, immunofluorescence and super-resolution microscopy","pmids":["33604307"],"confidence":"Medium","gaps":["Direct physical interaction of PfArf1 with AK2 versus indirect effect not resolved","Molecular basis of AK2 recognition at the ER subdomain unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological purpose of positioning an adenylate kinase at the PVM/tubovesicular network and its requirement for parasite viability remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No loss-of-function/essentiality data for AK2 in the corpus","Local role of AK2 nucleotide interconversion at the PVM not tested","No structural model of the targeting or catalytic domains"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["AK2–PfNMT heterodimer (in vitro) [#0]"],"partners":["PFNMT (N-MYRISTOYLTRANSFERASE) [#0]","PFRAB5B [#3, #4]","PFARF1 GTPASE [#4]"],"other_free_text":["N-terminal targeting module comprises N-myristoylation, a candidate S-palmitoylation cysteine, and a basic lysine cluster; N-terminal 37 aa sufficient for PPM targeting and translocation [#2]","Trafficking is N-myristoylation-dependent and PEXEL-independent; PfRab1b mutants do not affect AK2 transport [#3, #4]","Enzyme inhibited by P1,P5-(diadenosine-5')-pentaphosphate (IC50 ~200 nM); myristoylation enhances protein stability [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25909331","id":"PMC_25909331","title":"Alternative Protein Secretion in the Malaria Parasite Plasmodium falciparum.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25909331","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AK2","adenylate kinase 2","PfAK2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22819813","id":"PMC_22819813","title":"Subcellular localization of adenylate kinases in Plasmodium falciparum.","date":"2012","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/22819813","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AK2","PfAK2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18973776","id":"PMC_18973776","title":"Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a heterodimer with myristoyltransferase.","date":"2008","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18973776","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AK2","adenylate kinase 2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27316546","id":"PMC_27316546","title":"Plasmodium Rab5b is secreted to the cytoplasmic face of the tubovesicular network in infected red blood cells together with N-acylated adenylate kinase 2.","date":"2016","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/27316546","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["adenylate kinase 2","PfAK2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33604307","id":"PMC_33604307","title":"Rab5b-Associated Arf1 GTPase Regulates Export of N-Myristoylated Adenylate Kinase 2 From the Endoplasmic Reticulum in Plasmodium falciparum.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33604307","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AK2","adenylate kinase 2","PfAK2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6023,"output_tokens":1701,"usd":0.021792,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6730,"output_tokens":2627,"usd":0.049662,"stage2_stop_reason":"end_turn"},"total_usd":0.071454,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"Recombinantly produced AK2 (PF3D7_0816900) is a monomeric protein of 33 kDa with adenylate kinase enzymatic activity (specific activity of 10 U/mg with ATP and AMP as substrate pair) and is inhibited by P1,P5-(diadenosine-5')-pentaphosphate (IC50=200 nM). AK2 is N-myristoylated by P. falciparum N-myristoyltransferase (NMT), as demonstrated by co-expression in E. coli and mass spectrometry; myristoylation significantly enhances AK2 stability. Furthermore, AK2 and NMT form a heterodimeric complex in vitro.\",\n      \"method\": \"Recombinant protein production, in vitro enzymatic assay, co-expression in E. coli, protein purification, mass spectrometry\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with substrate characterization, myristoylation confirmed by mass spectrometry, heterodimer formation directly demonstrated; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"18973776\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Using GFP-fusion proteins and live cell imaging, AK2 (PF3D7_0816900) was localized to the parasitophorous vacuole membrane (PVM) in P. falciparum, and this localization is driven by N-myristoylation.\",\n      \"method\": \"GFP-fusion protein expression, live cell fluorescence microscopy\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by live imaging with GFP fusions, single lab, replicated finding consistent with prior biochemical data\",\n      \"pmids\": [\"22819813\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Biochemical and microscopy analyses of AK2 (PF3D7_0816900) GFP-tagged variants showed that three N-terminal motifs — N-myristoylation, a cysteine potential S-palmitoylation site, and a stretch of basic (lysine) residues — are collectively involved in targeting AK2 to the parasite plasma membrane (PPM) and its translocation across the PPM into the parasitophorous vacuole (PV). The N-terminal 37 amino acids of AK2 alone are sufficient to target and translocate GFP across the PPM.\",\n      \"method\": \"GFP-tagged variant expression, biochemical fractionation, fluorescence microscopy, chimeric fusion protein analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple GFP variants and chimeric proteins analyzed, combined biochemical and imaging approaches, single lab\",\n      \"pmids\": [\"25909331\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Co-expression and confocal microscopy showed that AK2 (PF3D7_0816900) and PfRab5b are co-transported from a compartment near the endoplasmic reticulum to the tubovesicular network (TVN) via an N-myristoylation-dependent, non-classical membrane-trafficking pathway. Overexpression of PfRab5b abrogated transport of AK2 to the PVM and caused AK2 accumulation in punctate structures together with PfRab5b.\",\n      \"method\": \"Co-expression with destabilization-domain (DD)-tagged PfRab5b, selective membrane permeabilization, confocal microscopy\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic and imaging approaches including selective permeabilization and overexpression phenotype; single lab\",\n      \"pmids\": [\"27316546\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Genetic expression of active or inactive PfArf1 mutants specifically inhibited trafficking of AK2 (PF3D7_0816900) to the PVM, establishing that PfArf1 GTPase sorts AK2 at the ER into the PV-directed pathway. PfRab1b mutants did not affect AK2 transport. This defines the pathway as: AK2 is recognized at an ER subdomain by PfArf1 and directed toward the PV independently of the PEXEL export pathway.\",\n      \"method\": \"Co-immunoprecipitation with mass spectrometry to identify PfRab5b-associated proteins, expression of constitutively active/inactive GTPase mutants, indirect immunofluorescence assay, super-resolution microscopy\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via active/inactive mutants combined with co-IP/MS and super-resolution imaging; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"33604307\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum AK2 (PF3D7_0816900) is a monomeric 33 kDa adenylate kinase that catalyzes ATP+AMP↔2 ADP; its N-terminus carries a myristoylation signal (modified by PfNMT, which also forms a heterodimer with AK2), a palmitoylation site, and a basic lysine cluster that together drive targeting to the parasite plasma membrane and translocation across it into the parasitophorous vacuole, with final delivery to the PVM/tubovesicular network regulated by PfArf1-mediated sorting from the ER via an N-myristoylation-dependent, PEXEL-independent trafficking pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AK2 (PF3D7_0816900) is a monomeric 33 kDa adenylate kinase of Plasmodium falciparum that catalyzes the interconversion of ATP and AMP to ADP and is inhibited by P1,P5-(diadenosine-5')-pentaphosphate [#0]. Its N-terminus is N-myristoylated by P. falciparum N-myristoyltransferase (with which AK2 forms a heterodimer in vitro), a modification that stabilizes the enzyme [#0], and together with a potential S-palmitoylation cysteine and a basic lysine cluster constitutes a targeting module: the N-terminal 37 residues alone are sufficient to direct AK2 to the parasite plasma membrane and drive its translocation across it into the parasitophorous vacuole [#2]. Downstream of the plasma membrane, AK2 is delivered to the parasitophorous vacuole membrane and tubovesicular network by an N-myristoylation-dependent, PEXEL-independent trafficking route: it is sorted at an ER subdomain by the PfArf1 GTPase toward the PV [#4] and co-transported with PfRab5b to the tubovesicular network, with PfRab5b overexpression rerouting AK2 into punctate structures and blocking its arrival at the PVM [#3, #1]. The physiological consequence of AK2 enzymatic activity at these membranes has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Establishing that PF3D7_0816900 is a bona fide, monomeric adenylate kinase whose N-terminus is myristoylated by parasite NMT answered whether the protein is enzymatically active and post-translationally lipidated.\",\n      \"evidence\": \"Recombinant protein production, in vitro adenylate kinase assay with inhibitor characterization, co-expression with NMT in E. coli, mass spectrometry\",\n      \"pmids\": [\"18973776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological substrate flux and role of AK2 activity in parasite energy metabolism not addressed\", \"Functional significance of the AK2–NMT heterodimer in vivo unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Localizing AK2 to the parasitophorous vacuole membrane and linking that localization to N-myristoylation answered where the enzyme resides and implicated its lipid modification in targeting.\",\n      \"evidence\": \"GFP-fusion protein expression and live cell fluorescence microscopy\",\n      \"pmids\": [\"22819813\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting myristoylation to PVM delivery not resolved at this stage\", \"Single-lab GFP-fusion result without endogenous tag validation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Dissecting the N-terminal targeting elements answered how AK2 is directed to and translocated across the plasma membrane, identifying a three-motif code.\",\n      \"evidence\": \"GFP-tagged variants and chimeric fusions, biochemical fractionation, fluorescence microscopy\",\n      \"pmids\": [\"25909331\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Machinery that recognizes the palmitoylation and lysine motifs not identified\", \"Mechanism of translocation across the plasma membrane not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrating co-transport with PfRab5b from an ER-proximal compartment to the tubovesicular network answered which trafficking route carries AK2 beyond the plasma membrane.\",\n      \"evidence\": \"Co-expression with DD-tagged PfRab5b, selective membrane permeabilization, confocal microscopy, PfRab5b overexpression phenotype\",\n      \"pmids\": [\"27316546\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether PfRab5b directly binds AK2 or acts indirectly not established\", \"Cargo-recognition step at the ER not defined at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying PfArf1 as the GTPase that sorts AK2 at the ER answered how AK2 enters the PV-directed, PEXEL-independent pathway and distinguished it from PfRab1b-dependent routes.\",\n      \"evidence\": \"Co-IP/MS of PfRab5b-associated proteins, constitutively active/inactive GTPase mutants, immunofluorescence and super-resolution microscopy\",\n      \"pmids\": [\"33604307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction of PfArf1 with AK2 versus indirect effect not resolved\", \"Molecular basis of AK2 recognition at the ER subdomain unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological purpose of positioning an adenylate kinase at the PVM/tubovesicular network and its requirement for parasite viability remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No loss-of-function/essentiality data for AK2 in the corpus\", \"Local role of AK2 nucleotide interconversion at the PVM not tested\", \"No structural model of the targeting or catalytic domains\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004017\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005524\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [1, 3, 4]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006165\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\n      \"AK2–PfNMT heterodimer (in vitro) [#0]\"\n    ],\n    \"partners\": [\n      \"PfNMT (N-myristoyltransferase) [#0]\",\n      \"PfRab5b [#3, #4]\",\n      \"PfArf1 GTPase [#4]\"\n    ],\n    \"other_free_text\": [\n      \"N-terminal targeting module comprises N-myristoylation, a candidate S-palmitoylation cysteine, and a basic lysine cluster; N-terminal 37 aa sufficient for PPM targeting and translocation [#2]\",\n      \"Trafficking is N-myristoylation-dependent and PEXEL-independent; PfRab1b mutants do not affect AK2 transport [#3, #4]\",\n      \"Enzyme inhibited by P1,P5-(diadenosine-5')-pentaphosphate (IC50 ~200 nM); myristoylation enhances protein stability [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0816900","name":null,"product":"adenylate kinase 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0713900","name":null,"product":"adenylate kinase 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0503500","name":null,"product":"adenylate kinase 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AK2","evaluation":null}