{"gene":"PMF1","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2001,"finding":"The interaction between transcription factors Nrf-2 and PMF-1 is mediated through binding of the leucine-zipper region of Nrf-2 and a C-terminal coiled-coil region of PMF-1 (which does not contain a leucine zipper). Mutations interrupting either the leucine zipper of Nrf-2 or the coiled-coil region of PMF-1 abolished their interaction and abrogated transcriptional regulation of the SSAT gene.","method":"Mutagenesis of leucine-zipper and coiled-coil domains combined with transcriptional reporter assays and protein interaction studies","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site/domain mutagenesis with functional readout (transcription assay), single lab but two orthogonal methods (interaction + transcription)","pmids":["11256947"],"is_preprint":false},{"year":2006,"finding":"Purified PMF-1 does not bind PRE sequences in the 5'-flanking region of the mouse 4E-BP1 gene on its own, but when added together with Nrf-2, decreases the magnitude of the gel shift for the PRE at -2060, indicating that PMF-1 modulates Nrf-2 binding to this regulatory element. CSN-7 did not interact with these sequences and did not inhibit protein/DNA interaction.","method":"Electrophoretic mobility shift assay (EMSA) and supershift assay with purified PMF-1 and Nrf-2 proteins","journal":"Life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean in vitro EMSA with purified proteins, single lab, single method","pmids":["16647090"],"is_preprint":false}],"current_model":"PMF-1 (polyamine modulated factor-1) functions as a transcriptional co-regulator of polyamine-responsive genes (SSAT, 4E-BP1) by interacting with Nrf-2 through its C-terminal coiled-coil domain, which binds the leucine-zipper of Nrf-2; this heteromeric complex binds polyamine-responsive elements (PREs) in gene promoters, and disruption of either interaction domain abolishes SSAT transcriptional regulation."},"narrative":{"mechanistic_narrative":"PMF1 (polyamine modulated factor-1) functions as a transcriptional co-regulator of polyamine-responsive genes by partnering with the transcription factor Nrf-2 [PMID:11256947]. The two proteins associate through binding of the leucine-zipper region of Nrf-2 to a C-terminal coiled-coil region of PMF-1 that itself lacks a leucine zipper, and mutations disrupting either domain abolish the interaction and abrogate transcriptional regulation of the SSAT gene [PMID:11256947]. PMF-1 does not bind polyamine-responsive element (PRE) DNA on its own; rather, it modulates Nrf-2 binding to a PRE in the 4E-BP1 promoter, altering the Nrf-2/DNA complex when added together with Nrf-2 [PMID:16647090]. Beyond this co-regulatory mechanism at PREs, no further molecular detail has been characterized in the available corpus.","teleology":[{"year":2001,"claim":"Established how PMF-1 physically engages a transcription factor and links that interaction to gene regulation, defining the structural basis of the PMF-1/Nrf-2 partnership.","evidence":"Domain mutagenesis of the Nrf-2 leucine zipper and PMF-1 coiled-coil with protein interaction and SSAT transcriptional reporter assays","pmids":["11256947"],"confidence":"High","gaps":["Does not resolve whether the interaction is direct or requires additional factors in vivo","No structural model of the coiled-coil/leucine-zipper interface","Mechanism by which polyamines control this complex was not defined"]},{"year":2006,"claim":"Clarified PMF-1's role at DNA, showing it is not a direct PRE-binding factor but a modulator of Nrf-2's DNA-binding behavior.","evidence":"EMSA and supershift with purified PMF-1 and Nrf-2 on the mouse 4E-BP1 PRE at -2060","pmids":["16647090"],"confidence":"Medium","gaps":["Single in vitro method without cellular confirmation of the modulated complex","Functional consequence of altered gel shift for 4E-BP1 transcription not established","Whether PMF-1 enters the DNA-bound complex or acts only off-DNA is unresolved"]},{"year":null,"claim":"The polyamine-sensing step that couples cellular polyamine levels to PMF-1/Nrf-2 activity at PREs remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identified polyamine-binding component or signal-transduction link in the captured corpus","Genome-wide set of PMF-1-regulated PRE target genes not defined","No structural data on the PMF-1/Nrf-2/DNA assembly"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1]}],"localization":[],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["NFE2L2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6P1K2","full_name":"Polyamine-modulated factor 1","aliases":[],"length_aa":205,"mass_kda":23.3,"function":"Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. May act as a cotranscription partner of NFE2L2 involved in regulation of polyamine-induced transcription of SSAT","subcellular_location":"Nucleus; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/Q6P1K2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/PMF1","classification":"Common Essential","n_dependent_lines":1201,"n_total_lines":1208,"dependency_fraction":0.9942052980132451},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PMF1","total_profiled":1310},"omim":[{"mim_id":"618085","title":"POLYAMINE-MODULATED FACTOR 1-BINDING PROTEIN 1; PMFBP1","url":"https://www.omim.org/entry/618085"},{"mim_id":"616009","title":"COP9 SIGNALOSOME, SUBUNIT 7A; COPS7A","url":"https://www.omim.org/entry/616009"},{"mim_id":"609178","title":"MIS12 KINETOCHORE COMPLEX COMPONENT; MIS12","url":"https://www.omim.org/entry/609178"},{"mim_id":"609176","title":"POLYAMINE-MODULATED FACTOR 1; PMF1","url":"https://www.omim.org/entry/609176"},{"mim_id":"609175","title":"DSN1, MIS12 KINETOCHORE COMPLEX COMPONENT; DSN1","url":"https://www.omim.org/entry/609175"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PMF1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q6P1K2","domains":[{"cath_id":"-","chopping":"35-118","consensus_level":"high","plddt":95.6799,"start":35,"end":118},{"cath_id":"1.20.5","chopping":"171-205","consensus_level":"medium","plddt":88.5271,"start":171,"end":205}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P1K2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P1K2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P1K2-F1-predicted_aligned_error_v6.png","plddt_mean":87.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PMF1","jax_strain_url":"https://www.jax.org/strain/search?query=PMF1"},"sequence":{"accession":"Q6P1K2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6P1K2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6P1K2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P1K2"}},"corpus_meta":[{"pmid":"11256947","id":"PMC_11256947","title":"Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N1-acetyltransferase (SSAT) gene.","date":"2001","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11256947","citation_count":54,"is_preprint":false},{"pmid":"18245244","id":"PMC_18245244","title":"Discovery of the autonomously replicating plasmid pMF1 from Myxococcus fulvus and development of a gene cloning system in Myxococcus xanthus.","date":"2008","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18245244","citation_count":39,"is_preprint":false},{"pmid":"10708368","id":"PMC_10708368","title":"A new single-copy mycobacterial plasmid, pMF1, from Mycobacterium fortuitum which is compatible with the pAL5000 replicon.","date":"2000","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/10708368","citation_count":39,"is_preprint":false},{"pmid":"19088041","id":"PMC_19088041","title":"Identification of PMF1 methylation in association with bladder cancer progression.","date":"2008","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/19088041","citation_count":31,"is_preprint":false},{"pmid":"22174771","id":"PMC_22174771","title":"Characterization of the partitioning system of Myxococcus plasmid pMF1.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22174771","citation_count":10,"is_preprint":false},{"pmid":"30131946","id":"PMC_30131946","title":"A Post-segregational Killing Mechanism for Maintaining Plasmid PMF1 in Its Myxococcus fulvus Host.","date":"2018","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30131946","citation_count":9,"is_preprint":false},{"pmid":"22537554","id":"PMC_22537554","title":"Characterization of the replication origin of the myxobacterial self-replicative plasmid pMF1.","date":"2012","source":"Plasmid","url":"https://pubmed.ncbi.nlm.nih.gov/22537554","citation_count":9,"is_preprint":false},{"pmid":"31396257","id":"PMC_31396257","title":"The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population.","date":"2019","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31396257","citation_count":7,"is_preprint":false},{"pmid":"16647090","id":"PMC_16647090","title":"Analysis of the interactions of Nrf-2, PMF-1, and CSN-7 with the 5'-flanking sequence of the mouse 4E-BP1 gene.","date":"2006","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/16647090","citation_count":6,"is_preprint":false},{"pmid":"33519784","id":"PMC_33519784","title":"ParC, a New Partitioning Protein, Is Necessary for the Active Form of ParA From Myxococcus pMF1 Plasmid.","date":"2021","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33519784","citation_count":5,"is_preprint":false},{"pmid":"36197289","id":"PMC_36197289","title":"Allyl Aryl Ether Cleavage by Blautia sp. MRG-PMF1 Cocorrinoid O-Demethylase.","date":"2022","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36197289","citation_count":2,"is_preprint":false},{"pmid":"26358007","id":"PMC_26358007","title":"Screening for recombinants of Crambe abyssynica after transformation by the pMF1 marker-free vector based on chemical selection and meristematic regeneration.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26358007","citation_count":2,"is_preprint":false},{"pmid":"39545733","id":"PMC_39545733","title":"Putative evolution of Myxococcus fulvus 124B02 plasmid pMF1 from a chromosomal segment in another Myxococcus species.","date":"2024","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/39545733","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9254,"output_tokens":653,"usd":0.018779,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6986,"output_tokens":1226,"usd":0.03279,"stage2_stop_reason":"end_turn"},"total_usd":0.051569,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"The interaction between transcription factors Nrf-2 and PMF-1 is mediated through binding of the leucine-zipper region of Nrf-2 and a C-terminal coiled-coil region of PMF-1 (which does not contain a leucine zipper). Mutations interrupting either the leucine zipper of Nrf-2 or the coiled-coil region of PMF-1 abolished their interaction and abrogated transcriptional regulation of the SSAT gene.\",\n      \"method\": \"Mutagenesis of leucine-zipper and coiled-coil domains combined with transcriptional reporter assays and protein interaction studies\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site/domain mutagenesis with functional readout (transcription assay), single lab but two orthogonal methods (interaction + transcription)\",\n      \"pmids\": [\"11256947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Purified PMF-1 does not bind PRE sequences in the 5'-flanking region of the mouse 4E-BP1 gene on its own, but when added together with Nrf-2, decreases the magnitude of the gel shift for the PRE at -2060, indicating that PMF-1 modulates Nrf-2 binding to this regulatory element. CSN-7 did not interact with these sequences and did not inhibit protein/DNA interaction.\",\n      \"method\": \"Electrophoretic mobility shift assay (EMSA) and supershift assay with purified PMF-1 and Nrf-2 proteins\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean in vitro EMSA with purified proteins, single lab, single method\",\n      \"pmids\": [\"16647090\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PMF-1 (polyamine modulated factor-1) functions as a transcriptional co-regulator of polyamine-responsive genes (SSAT, 4E-BP1) by interacting with Nrf-2 through its C-terminal coiled-coil domain, which binds the leucine-zipper of Nrf-2; this heteromeric complex binds polyamine-responsive elements (PREs) in gene promoters, and disruption of either interaction domain abolishes SSAT transcriptional regulation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PMF1 (polyamine modulated factor-1) functions as a transcriptional co-regulator of polyamine-responsive genes by partnering with the transcription factor Nrf-2 [#0]. The two proteins associate through binding of the leucine-zipper region of Nrf-2 to a C-terminal coiled-coil region of PMF-1 that itself lacks a leucine zipper, and mutations disrupting either domain abolish the interaction and abrogate transcriptional regulation of the SSAT gene [#0]. PMF-1 does not bind polyamine-responsive element (PRE) DNA on its own; rather, it modulates Nrf-2 binding to a PRE in the 4E-BP1 promoter, altering the Nrf-2/DNA complex when added together with Nrf-2 [#1]. Beyond this co-regulatory mechanism at PREs, no further molecular detail has been characterized in the available corpus.\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established how PMF-1 physically engages a transcription factor and links that interaction to gene regulation, defining the structural basis of the PMF-1/Nrf-2 partnership.\",\n      \"evidence\": \"Domain mutagenesis of the Nrf-2 leucine zipper and PMF-1 coiled-coil with protein interaction and SSAT transcriptional reporter assays\",\n      \"pmids\": [\"11256947\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not resolve whether the interaction is direct or requires additional factors in vivo\",\n        \"No structural model of the coiled-coil/leucine-zipper interface\",\n        \"Mechanism by which polyamines control this complex was not defined\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Clarified PMF-1's role at DNA, showing it is not a direct PRE-binding factor but a modulator of Nrf-2's DNA-binding behavior.\",\n      \"evidence\": \"EMSA and supershift with purified PMF-1 and Nrf-2 on the mouse 4E-BP1 PRE at -2060\",\n      \"pmids\": [\"16647090\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single in vitro method without cellular confirmation of the modulated complex\",\n        \"Functional consequence of altered gel shift for 4E-BP1 transcription not established\",\n        \"Whether PMF-1 enters the DNA-bound complex or acts only off-DNA is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The polyamine-sensing step that couples cellular polyamine levels to PMF-1/Nrf-2 activity at PREs remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No identified polyamine-binding component or signal-transduction link in the captured corpus\",\n        \"Genome-wide set of PMF-1-regulated PRE target genes not defined\",\n        \"No structural data on the PMF-1/Nrf-2/DNA assembly\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"NFE2L2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}