{"gene":"ZFP1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":1989,"finding":"Mouse Zfp-1 (Zfp1) encodes a protein containing 7 C2H2 zinc fingers and two helix-turn-helix motifs, structurally related to the Drosophila segmentation gene Krüppel; the gene is ubiquitously expressed during embryogenesis with peak expression at day 12, and maps to the 16q region of mouse chromosome 8.","method":"cDNA cloning, nucleotide and amino acid sequence analysis, Northern blot expression analysis, chromosomal mapping","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — cDNA cloning and sequence characterization with expression analysis; single lab, structural inference without functional mutagenesis validation","pmids":["2574853"],"is_preprint":false},{"year":2018,"finding":"The human KRAB-type zinc-finger protein PITA (ZFP1) physically interacts with p53 and specifically suppresses transcription of the p53 target gene TIGAR (a glycolysis regulator), but not SCO2; PITA transgenic mice exhibit increased PFK1 activity and elevated glycolytic rate. Upon glucose starvation, PITA dissociates from p53, allowing p53 activation and TIGAR induction which inhibits aerobic glycolysis. The dynamic dissociation of PITA from p53 under metabolic stress is dependent on ATM kinase-mediated phosphorylation of PITA.","method":"Co-immunoprecipitation, transgenic mouse phenotyping (PFK1 activity, glycolytic rate), luciferase reporter transcription assays, glucose starvation experiments, ATM kinase inhibitor experiments, PITA/PISA depletion in colorectal cancer cells","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing direct p53 interaction, transgenic mouse metabolic phenotyping, mechanistic dissection of ATM-dependent phosphorylation and dissociation, multiple orthogonal methods in a single rigorous study","pmids":["29467382"],"is_preprint":false}],"current_model":"Human ZFP1/PITA is a KRAB-type C2H2 zinc-finger protein that physically interacts with p53 and selectively represses transcription of the p53 glycolysis target TIGAR; under glucose starvation, ATM kinase-mediated phosphorylation of PITA triggers its dissociation from p53, de-repressing TIGAR and inhibiting aerobic glycolysis, thereby placing PITA as a stress-responsive, selective negative regulator of p53-mediated metabolic control."},"narrative":{"mechanistic_narrative":"ZFP1 (human PITA) is a KRAB-type C2H2 zinc-finger transcriptional repressor that functions as a stress-responsive, selective negative regulator of p53-mediated metabolic control [PMID:29467382]. PITA physically interacts with p53 and specifically suppresses transcription of the p53 glycolysis-regulating target gene TIGAR, while sparing other p53 targets such as SCO2; consistent with this, PITA transgenic mice show increased PFK1 activity and elevated glycolytic rate [PMID:29467382]. Under glucose starvation, ATM kinase-mediated phosphorylation of PITA drives its dissociation from p53, permitting p53 activation and TIGAR induction that inhibits aerobic glycolysis, thereby coupling metabolic stress sensing to p53 transcriptional output [PMID:29467382]. The protein's domain architecture—seven C2H2 zinc fingers with Krüppel-like organization—was defined in the mouse ortholog [PMID:2574853]. Beyond this p53/TIGAR axis and the structural characterization, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":1989,"claim":"Established the molecular identity and domain architecture of the gene, defining it as a Krüppel-related C2H2 zinc-finger protein with potential DNA-binding/transcription-factor function.","evidence":"cDNA cloning, sequence analysis, Northern blot expression profiling and chromosomal mapping of mouse Zfp1","pmids":["2574853"],"confidence":"Medium","gaps":["Structural assignment of zinc fingers was inferred from sequence without functional mutagenesis","No DNA target or binding specificity defined","No transcriptional or biochemical activity demonstrated"]},{"year":2018,"claim":"Resolved the functional role of human PITA/ZFP1 as a p53-binding repressor that selectively silences TIGAR to promote glycolysis, and defined ATM phosphorylation as the switch that releases this repression under glucose starvation.","evidence":"Reciprocal Co-IP, luciferase reporter assays, transgenic mouse metabolic phenotyping (PFK1 activity, glycolytic rate), glucose starvation and ATM inhibitor experiments, and PITA depletion in colorectal cancer cells","pmids":["29467382"],"confidence":"High","gaps":["Direct DNA binding of PITA at the TIGAR locus versus indirect repression via p53 not fully distinguished","Specific ATM phosphosite(s) on PITA not mapped","Basis for selectivity toward TIGAR over other p53 targets such as SCO2 unexplained"]},{"year":null,"claim":"How PITA achieves promoter selectivity among p53 targets and whether it engages chromatin or co-repressor machinery via its KRAB/zinc-finger domains remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the PITA-p53 interface","No genome-wide DNA-binding map","Co-repressor partners of the KRAB domain not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1]}],"complexes":[],"partners":["TP53"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6P2D0","full_name":"Zinc finger protein 1 homolog","aliases":["Zinc finger protein 475"],"length_aa":407,"mass_kda":47.5,"function":"May be involved in transcriptional regulation","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q6P2D0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZFP1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CBX1","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"IPO8","stoichiometry":0.2},{"gene":"TRIM28","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ZFP1","total_profiled":1310},"omim":[{"mim_id":"617230","title":"ZFP1 ZINC FINGER PROTEIN; ZFP1","url":"https://www.omim.org/entry/617230"},{"mim_id":"194538","title":"ZINC FINGER PROTEIN 10; ZNF10","url":"https://www.omim.org/entry/194538"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZFP1"},"hgnc":{"alias_symbol":["PITA","FLJ34243","ZNF475"],"prev_symbol":[]},"alphafold":{"accession":"Q6P2D0","domains":[{"cath_id":"3.30.160.60","chopping":"183-237","consensus_level":"medium","plddt":83.2735,"start":183,"end":237}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2D0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2D0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2D0-F1-predicted_aligned_error_v6.png","plddt_mean":65.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZFP1","jax_strain_url":"https://www.jax.org/strain/search?query=ZFP1"},"sequence":{"accession":"Q6P2D0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6P2D0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6P2D0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2D0"}},"corpus_meta":[{"pmid":"11090207","id":"PMC_11090207","title":"tA single amino acid difference distinguishes resistant and susceptible alleles of the rice blast resistance gene Pi-ta.","date":"2000","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/11090207","citation_count":342,"is_preprint":false},{"pmid":"11090206","id":"PMC_11090206","title":"A telomeric avirulence gene determines efficacy for the rice blast resistance gene Pi-ta.","date":"2000","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/11090206","citation_count":339,"is_preprint":false},{"pmid":"21829350","id":"PMC_21829350","title":"Multiple translocation of the AVR-Pita effector gene among chromosomes of the rice blast fungus Magnaporthe oryzae and related species.","date":"2011","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/21829350","citation_count":167,"is_preprint":false},{"pmid":"11489853","id":"PMC_11489853","title":"Characterization of PitA and PitB from Escherichia coli.","date":"2001","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/11489853","citation_count":109,"is_preprint":false},{"pmid":"14704173","id":"PMC_14704173","title":"Germline cell death is inhibited by P-element insertions disrupting the dcp-1/pita nested gene pair in Drosophila.","date":"2003","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/14704173","citation_count":101,"is_preprint":false},{"pmid":"25342723","id":"PMC_25342723","title":"Two new insulator proteins, Pita and ZIPIC, target CP190 to chromatin.","date":"2014","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/25342723","citation_count":90,"is_preprint":false},{"pmid":"17387027","id":"PMC_17387027","title":"Instability of the Magnaporthe oryzae avirulence gene AVR-Pita alters virulence.","date":"2007","source":"Fungal genetics and biology : FG & B","url":"https://pubmed.ncbi.nlm.nih.gov/17387027","citation_count":89,"is_preprint":false},{"pmid":"18393625","id":"PMC_18393625","title":"Genome organization and evolution of the AVR-Pita avirulence gene family in the Magnaporthe grisea species complex.","date":"2008","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/18393625","citation_count":88,"is_preprint":false},{"pmid":"27137890","id":"PMC_27137890","title":"Architectural proteins Pita, Zw5,and ZIPIC contain homodimerization domain and support specific long-range interactions in Drosophila.","date":"2016","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/27137890","citation_count":60,"is_preprint":false},{"pmid":"33443630","id":"PMC_33443630","title":"The Fungal Effector Avr-Pita Suppresses Innate Immunity by Increasing COX Activity in Rice Mitochondria.","date":"2021","source":"Rice (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/33443630","citation_count":49,"is_preprint":false},{"pmid":"30276893","id":"PMC_30276893","title":"The small protein MgtS and small RNA MgrR modulate the PitA phosphate symporter to boost intracellular magnesium levels.","date":"2018","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30276893","citation_count":47,"is_preprint":false},{"pmid":"18943978","id":"PMC_18943978","title":"Rice Pi-ta gene Confers Resistance to the Major Pathotypes of the Rice Blast Fungus in the United States.","date":"2004","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/18943978","citation_count":44,"is_preprint":false},{"pmid":"19054109","id":"PMC_19054109","title":"Expression of the PitA phosphate/metal transporter of Escherichia coli is responsive to zinc and inorganic phosphate levels.","date":"2008","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/19054109","citation_count":39,"is_preprint":false},{"pmid":"18944075","id":"PMC_18944075","title":"Natural Variation at the Pi-ta Rice Blast Resistance Locus.","date":"2003","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/18944075","citation_count":39,"is_preprint":false},{"pmid":"29467382","id":"PMC_29467382","title":"KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration.","date":"2018","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/29467382","citation_count":37,"is_preprint":false},{"pmid":"32170462","id":"PMC_32170462","title":"The broad-spectrum rice blast resistance (R) gene Pita2 encodes a novel R protein unique from Pita.","date":"2020","source":"Rice (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/32170462","citation_count":33,"is_preprint":false},{"pmid":"28619827","id":"PMC_28619827","title":"Architectural protein Pita cooperates with dCTCF in organization of functional boundaries in Bithorax complex.","date":"2017","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/28619827","citation_count":32,"is_preprint":false},{"pmid":"27070427","id":"PMC_27070427","title":"Coevolutionary Dynamics of Rice Blast Resistance Gene Pi-ta and Magnaporthe oryzae Avirulence Gene AVR-Pita 1.","date":"2016","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/27070427","citation_count":30,"is_preprint":false},{"pmid":"23189244","id":"PMC_23189244","title":"Tellurite enters Escherichia coli mainly through the PitA phosphate transporter.","date":"2012","source":"MicrobiologyOpen","url":"https://pubmed.ncbi.nlm.nih.gov/23189244","citation_count":28,"is_preprint":false},{"pmid":"19000005","id":"PMC_19000005","title":"Haplotype diversity at the Pi-ta locus in cultivated rice and its wild relatives.","date":"2008","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/19000005","citation_count":28,"is_preprint":false},{"pmid":"29665158","id":"PMC_29665158","title":"Peanut gastrointestinal delivery oral immunotherapy in adolescents: Results of the build-up phase of a randomized, double-blind, placebo-controlled trial (PITA study).","date":"2018","source":"Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/29665158","citation_count":27,"is_preprint":false},{"pmid":"22043312","id":"PMC_22043312","title":"Molecular evolution of the rice blast resistance gene Pi-ta in invasive weedy rice in the USA.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22043312","citation_count":26,"is_preprint":false},{"pmid":"33752739","id":"PMC_33752739","title":"Mechanism and functional role of the interaction between CP190 and the architectural protein Pita in Drosophila melanogaster.","date":"2021","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/33752739","citation_count":24,"is_preprint":false},{"pmid":"2574853","id":"PMC_2574853","title":"Structure, expression and chromosomal localization of Zfp-1, a murine zinc finger protein gene.","date":"1989","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2574853","citation_count":24,"is_preprint":false},{"pmid":"25092032","id":"PMC_25092032","title":"Role of an archaeal PitA transporter in the copper and arsenic resistance of Metallosphaera sedula, an extreme thermoacidophile.","date":"2014","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/25092032","citation_count":22,"is_preprint":false},{"pmid":"19623205","id":"PMC_19623205","title":"Artificial introgression of a large chromosome fragment around the rice blast resistance gene Pi-ta in backcross progeny and several elite rice cultivars.","date":"2009","source":"Heredity","url":"https://pubmed.ncbi.nlm.nih.gov/19623205","citation_count":20,"is_preprint":false},{"pmid":"30630094","id":"PMC_30630094","title":"The Cys2His2 zinc finger protein Zfp1 regulates sexual reproduction and virulence in Cryptococcus neoformans.","date":"2019","source":"Fungal genetics and biology : FG & B","url":"https://pubmed.ncbi.nlm.nih.gov/30630094","citation_count":18,"is_preprint":false},{"pmid":"26211961","id":"PMC_26211961","title":"The ActP acetate transporter acts prior to the PitA phosphate carrier in tellurite uptake by Escherichia coli.","date":"2015","source":"Microbiological research","url":"https://pubmed.ncbi.nlm.nih.gov/26211961","citation_count":18,"is_preprint":false},{"pmid":"38834685","id":"PMC_38834685","title":"The unconventional resistance protein PTR recognizes the Magnaporthe oryzae effector AVR-Pita in an allele-specific manner.","date":"2024","source":"Nature plants","url":"https://pubmed.ncbi.nlm.nih.gov/38834685","citation_count":17,"is_preprint":false},{"pmid":"20003273","id":"PMC_20003273","title":"The low-affinity phosphate transporter PitA is dispensable for in vitro growth of Mycobacterium smegmatis.","date":"2009","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20003273","citation_count":17,"is_preprint":false},{"pmid":"24633351","id":"PMC_24633351","title":"Transposon-based high sequence diversity in Avr-Pita alleles increases the potential for pathogenicity of Magnaporthe oryzae populations.","date":"2014","source":"Functional & integrative genomics","url":"https://pubmed.ncbi.nlm.nih.gov/24633351","citation_count":16,"is_preprint":false},{"pmid":"23818197","id":"PMC_23818197","title":"Molecular diversity in rice blast resistance gene Pi-ta makes it highly effective against dynamic population of Magnaporthe oryzae.","date":"2013","source":"Functional & integrative genomics","url":"https://pubmed.ncbi.nlm.nih.gov/23818197","citation_count":16,"is_preprint":false},{"pmid":"15547953","id":"PMC_15547953","title":"Morphological irregularities and features of resistance to apoptosis in the dcp-1/pita double mutated egg chambers during Drosophila oogenesis.","date":"2005","source":"Cell motility and the cytoskeleton","url":"https://pubmed.ncbi.nlm.nih.gov/15547953","citation_count":15,"is_preprint":false},{"pmid":"30764397","id":"PMC_30764397","title":"Determination of Resistance Spectra of the Pi-ta and Pi-k Genes to U.S. Races of Magnaporthe oryzae Causing Rice Blast in a Recombinant Inbred Line Population.","date":"2009","source":"Plant disease","url":"https://pubmed.ncbi.nlm.nih.gov/30764397","citation_count":13,"is_preprint":false},{"pmid":"32210583","id":"PMC_32210583","title":"Up-Regulation of Hsa_circ_0008792 Inhibits Osteosarcoma Cell Invasion and Migration and Promotes Apoptosis by Regulating Hsa-miR-711/ZFP1.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32210583","citation_count":11,"is_preprint":false},{"pmid":"24450460","id":"PMC_24450460","title":"Effectiveness and durability of the rice pi-ta gene in Yunnan province of China.","date":"2014","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/24450460","citation_count":11,"is_preprint":false},{"pmid":"29658844","id":"PMC_29658844","title":"Functional Interactions Between Major Rice Blast Resistance Genes, Pi-ta and Pi-b, and Minor Blast Resistance Quantitative Trait Loci.","date":"2018","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/29658844","citation_count":11,"is_preprint":false},{"pmid":"36346250","id":"PMC_36346250","title":"Pseudomonas aeruginosa Phosphate Transporter PitA (PA4292) Controls Susceptibility to Aminoglycoside Antibiotics by Regulating the Proton Motive Force.","date":"2022","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/36346250","citation_count":10,"is_preprint":false},{"pmid":"25645557","id":"PMC_25645557","title":"Ugp and PitA participate in the selection of PHO-constitutive mutants.","date":"2015","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/25645557","citation_count":8,"is_preprint":false},{"pmid":"37184394","id":"PMC_37184394","title":"PitA Controls the H2- and H3-T6SSs through PhoB in Pseudomonas aeruginosa.","date":"2023","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37184394","citation_count":7,"is_preprint":false},{"pmid":"35159488","id":"PMC_35159488","title":"Effects of Tasting and Ingredient Information Statement on Acceptability, Elicited Emotions, and Willingness to Purchase: A Case of Pita Chips Containing Edible Cricket Protein.","date":"2022","source":"Foods (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35159488","citation_count":7,"is_preprint":false},{"pmid":"31929180","id":"PMC_31929180","title":"The adhesive PitA pilus protein from the early dental plaque colonizer Streptococcus oralis: expression, purification, crystallization and X-ray diffraction analysis.","date":"2020","source":"Acta crystallographica. Section F, Structural biology communications","url":"https://pubmed.ncbi.nlm.nih.gov/31929180","citation_count":7,"is_preprint":false},{"pmid":"36050368","id":"PMC_36050368","title":"Analysis of a rice blast resistance gene Pita-Fuhui2663 and development of selection marker.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36050368","citation_count":5,"is_preprint":false},{"pmid":"15346764","id":"PMC_15346764","title":"Medicago truncatula Mt-ZFP1 encoding a root enhanced zinc finger protein is regulated by cytokinin, abscisic acid and jasmonate, but not cold.","date":"2004","source":"DNA sequence : the journal of DNA sequencing and mapping","url":"https://pubmed.ncbi.nlm.nih.gov/15346764","citation_count":5,"is_preprint":false},{"pmid":"24905652","id":"PMC_24905652","title":"Nucleotide diversity of Pita, a major blast resistance gene and identification of its minimal promoter.","date":"2014","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/24905652","citation_count":5,"is_preprint":false},{"pmid":"25335927","id":"PMC_25335927","title":"Statistical inference of selection and divergence of the rice blast resistance gene Pi-ta.","date":"2014","source":"G3 (Bethesda, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/25335927","citation_count":5,"is_preprint":false},{"pmid":"35293272","id":"PMC_35293272","title":"Zfp1, a Cys2His2 zinc finger protein is required for meiosis initiation in Tetrahymena thermophila.","date":"2022","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/35293272","citation_count":3,"is_preprint":false},{"pmid":"37824582","id":"PMC_37824582","title":"The PitA protein contributes to colistin susceptibility in Pseudomonas aeruginosa.","date":"2023","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/37824582","citation_count":3,"is_preprint":false},{"pmid":"34676451","id":"PMC_34676451","title":"In silico molecular and morphological analysis of rice blast resistant gene Pi-ta in Sri Lankan rice germplasm.","date":"2021","source":"Journal, genetic engineering & biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/34676451","citation_count":3,"is_preprint":false},{"pmid":"35143673","id":"PMC_35143673","title":"Fitness benefits play a vital role in the retention of the Pi-ta susceptible alleles.","date":"2022","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35143673","citation_count":3,"is_preprint":false},{"pmid":"38992190","id":"PMC_38992190","title":"Zinc finger transcription factor ZFP1 is associated with growth, conidiation, osmoregulation, and virulence in the Polygonatum kingianum pathogen Fusarium oxysporum.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38992190","citation_count":2,"is_preprint":false},{"pmid":"37907574","id":"PMC_37907574","title":"Genetic and molecular analysis of leaf blast resistance in Tetep derived line RIL4 and its relationship to genes at Pita/Pita2 locus.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37907574","citation_count":2,"is_preprint":false},{"pmid":"35430802","id":"PMC_35430802","title":"The compliance of nutrition claims on pita bread in Lebanon and risk on public health: a cross-sectional study.","date":"2022","source":"BMC nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/35430802","citation_count":2,"is_preprint":false},{"pmid":"41291933","id":"PMC_41291933","title":"ZAD mediates chromatin binding and insulator activity of Drosophila Pita and can be replaced with the human ZFP276 ZAD-like domain.","date":"2025","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/41291933","citation_count":1,"is_preprint":false},{"pmid":"29318139","id":"PMC_29318139","title":"Effect of Buttermilk on the Physicochemical, Rheological, and Sensory Qualities of Pan and Pita Bread.","date":"2017","source":"International journal of food science","url":"https://pubmed.ncbi.nlm.nih.gov/29318139","citation_count":1,"is_preprint":false},{"pmid":"39457449","id":"PMC_39457449","title":"Exploring Distribution and Evolution of Pi-ta Haplotypes in Rice Landraces across Different Rice Cultivation Regions in Yunnan.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/39457449","citation_count":1,"is_preprint":false},{"pmid":"35347474","id":"PMC_35347474","title":"Identifying mutations in sd1, Pi54 and Pi-ta, and positively selected genes of TN1, the first semidwarf rice in Green Revolution.","date":"2022","source":"Botanical studies","url":"https://pubmed.ncbi.nlm.nih.gov/35347474","citation_count":1,"is_preprint":false},{"pmid":"41600128","id":"PMC_41600128","title":"Pyramiding Pita, Pigm, Pi2, and Xa23 to Develop Hybrid Rice with Dual Resistance to Rice Blast and Bacterial Blight.","date":"2026","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/41600128","citation_count":0,"is_preprint":false},{"pmid":"19137822","id":"PMC_19137822","title":"[Genetic diversity of AVR-pita alleles of rice blast fungus Magnaporthe grisea].","date":"2008","source":"Fen zi xi bao sheng wu xue bao = Journal of molecular cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19137822","citation_count":0,"is_preprint":false},{"pmid":"40952343","id":"PMC_40952343","title":"Identification of a Major Rice Blast Quantitative Trait Locus Containing Pita/Pi39(t)/Ptr in U.S. Black Hull Awn Weedy Rice.","date":"2026","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/40952343","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.02.15.25322352","title":"Factors Associated with Recurrent Malaria Episodes among Children Under Five at Kayunga Regional Referral Hospital in Kayunga District, Central Uganda","date":"2025-02-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.15.25322352","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":31290,"output_tokens":1460,"usd":0.057885,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7147,"output_tokens":1397,"usd":0.03533,"stage2_stop_reason":"end_turn"},"total_usd":0.093215,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the corpus, I need to identify papers about the human/mammalian gene ZFP1 (HGNC aliases: PITA, FLJ34243).\n\nLet me classify the papers:\n\n- Papers 1-3, 7-8, 10, 12, 14, 16, 18, 20, 22, 26, 29, 31-32, 34, 36-37, 43, 45-46, 49-50, 52, 56-60: Rice/fungal Pi-ta/AVR-Pita — EXCLUDE (plant/fungal genes, not the human ZFP1)\n- Papers 4, 11, 13, 19, 25, 28, 30, 38-40, 48: Bacterial/archaeal PitA phosphate transporters — EXCLUDE (prokaryotic, different gene)\n- Paper 5, 33: Drosophila pita (C2H2 zinc finger, nested with dcp-1) — possible ortholog context\n- Paper 6, 9, 17, 23, 54: Drosophila Pita as insulator/architectural protein — possible ortholog\n- Paper 15: Human PITA (alias PITA = ZFP1, KRAB-type zinc-finger) — INCLUDE (this is the human gene)\n- Paper 24: Mouse Zfp-1 — INCLUDE (likely ortholog)\n- Paper 27: Cryptococcus Zfp1 — EXCLUDE (fungal pathogen, incompatible function)\n- Paper 35: circRNA/miR study mentioning ZFP1 — EXCLUDE (non-protein locus product focus)\n- Paper 41: Food science pita chips — EXCLUDE\n- Paper 42: Streptococcus PitA pilus — EXCLUDE\n- Paper 44: Medicago Mt-ZFP1 — EXCLUDE (plant)\n- Paper 47: Tetrahymena Zfp1 — EXCLUDE (ciliate)\n- Paper 51: Fusarium ZFP1 — EXCLUDE (fungal pathogen)\n- Paper 53, 55: Pita bread — EXCLUDE\n- Paper 61: Malaria preprint — EXCLUDE\n\nThe Drosophila Pita papers (5, 6, 9, 17, 23, 54) describe a C2H2 zinc-finger insulator/architectural protein nested with dcp-1 — this matches the domain architecture of the human PITA/ZFP1 only partially. However, the human PITA (paper 15) is explicitly a KRAB-type zinc-finger protein interacting with p53. The Drosophila Pita has ZAD + C2H2 zinc fingers and functions as an insulator protein — this is a different architecture and function from the human gene. I'll treat these as non-ortholog (symbol collision in different metazoan lineages with divergent functions), and focus on paper 15 and paper 24 (mouse Zfp-1).\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1989,\n      \"finding\": \"Mouse Zfp-1 (Zfp1) encodes a protein containing 7 C2H2 zinc fingers and two helix-turn-helix motifs, structurally related to the Drosophila segmentation gene Krüppel; the gene is ubiquitously expressed during embryogenesis with peak expression at day 12, and maps to the 16q region of mouse chromosome 8.\",\n      \"method\": \"cDNA cloning, nucleotide and amino acid sequence analysis, Northern blot expression analysis, chromosomal mapping\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — cDNA cloning and sequence characterization with expression analysis; single lab, structural inference without functional mutagenesis validation\",\n      \"pmids\": [\"2574853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The human KRAB-type zinc-finger protein PITA (ZFP1) physically interacts with p53 and specifically suppresses transcription of the p53 target gene TIGAR (a glycolysis regulator), but not SCO2; PITA transgenic mice exhibit increased PFK1 activity and elevated glycolytic rate. Upon glucose starvation, PITA dissociates from p53, allowing p53 activation and TIGAR induction which inhibits aerobic glycolysis. The dynamic dissociation of PITA from p53 under metabolic stress is dependent on ATM kinase-mediated phosphorylation of PITA.\",\n      \"method\": \"Co-immunoprecipitation, transgenic mouse phenotyping (PFK1 activity, glycolytic rate), luciferase reporter transcription assays, glucose starvation experiments, ATM kinase inhibitor experiments, PITA/PISA depletion in colorectal cancer cells\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing direct p53 interaction, transgenic mouse metabolic phenotyping, mechanistic dissection of ATM-dependent phosphorylation and dissociation, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"29467382\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human ZFP1/PITA is a KRAB-type C2H2 zinc-finger protein that physically interacts with p53 and selectively represses transcription of the p53 glycolysis target TIGAR; under glucose starvation, ATM kinase-mediated phosphorylation of PITA triggers its dissociation from p53, de-repressing TIGAR and inhibiting aerobic glycolysis, thereby placing PITA as a stress-responsive, selective negative regulator of p53-mediated metabolic control.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZFP1 (human PITA) is a KRAB-type C2H2 zinc-finger transcriptional repressor that functions as a stress-responsive, selective negative regulator of p53-mediated metabolic control [#1]. PITA physically interacts with p53 and specifically suppresses transcription of the p53 glycolysis-regulating target gene TIGAR, while sparing other p53 targets such as SCO2; consistent with this, PITA transgenic mice show increased PFK1 activity and elevated glycolytic rate [#1]. Under glucose starvation, ATM kinase-mediated phosphorylation of PITA drives its dissociation from p53, permitting p53 activation and TIGAR induction that inhibits aerobic glycolysis, thereby coupling metabolic stress sensing to p53 transcriptional output [#1]. The protein's domain architecture—seven C2H2 zinc fingers with Krüppel-like organization—was defined in the mouse ortholog [#0]. Beyond this p53/TIGAR axis and the structural characterization, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1989,\n      \"claim\": \"Established the molecular identity and domain architecture of the gene, defining it as a Krüppel-related C2H2 zinc-finger protein with potential DNA-binding/transcription-factor function.\",\n      \"evidence\": \"cDNA cloning, sequence analysis, Northern blot expression profiling and chromosomal mapping of mouse Zfp1\",\n      \"pmids\": [\"2574853\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural assignment of zinc fingers was inferred from sequence without functional mutagenesis\",\n        \"No DNA target or binding specificity defined\",\n        \"No transcriptional or biochemical activity demonstrated\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved the functional role of human PITA/ZFP1 as a p53-binding repressor that selectively silences TIGAR to promote glycolysis, and defined ATM phosphorylation as the switch that releases this repression under glucose starvation.\",\n      \"evidence\": \"Reciprocal Co-IP, luciferase reporter assays, transgenic mouse metabolic phenotyping (PFK1 activity, glycolytic rate), glucose starvation and ATM inhibitor experiments, and PITA depletion in colorectal cancer cells\",\n      \"pmids\": [\"29467382\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct DNA binding of PITA at the TIGAR locus versus indirect repression via p53 not fully distinguished\",\n        \"Specific ATM phosphosite(s) on PITA not mapped\",\n        \"Basis for selectivity toward TIGAR over other p53 targets such as SCO2 unexplained\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PITA achieves promoter selectivity among p53 targets and whether it engages chromatin or co-repressor machinery via its KRAB/zinc-finger domains remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the PITA-p53 interface\",\n        \"No genome-wide DNA-binding map\",\n        \"Co-repressor partners of the KRAB domain not identified\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TP53\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}