{"gene":"LIAT1","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2014,"finding":"LIAT1 (Ligand of Ate1) directly binds the arginyltransferase Ate1, with higher affinity for Ate1 isoforms 1A7A and 1B7A; a conserved ~30-residue region of LIAT1 is required for this binding.","method":"Protein interaction studies (binding assays), isoform-specific affinity measurements, deletion/domain mapping","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding demonstrated with domain mapping and isoform specificity, single lab, multiple methods reported","pmids":["25369936"],"is_preprint":false},{"year":2014,"finding":"LIAT1 stimulates the in vitro N-terminal arginylation of a model substrate by Ate1, indicating a positive regulatory role in the N-end rule/Arg/N-degron pathway.","method":"In vitro arginylation assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro enzymatic assay, single lab, single method","pmids":["25369936"],"is_preprint":false},{"year":2020,"finding":"LIAT1's N-terminal half is an intrinsically disordered region (IDR) containing a low-complexity poly-K region that targets LIAT1 to the nucleolus and facilitates liquid-liquid phase separation (LLPS) there.","method":"Bimolecular fluorescence complementation, immunocytochemistry, domain deletion analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiments with functional domain mapping, single lab, two orthogonal methods","pmids":["33443146"],"is_preprint":false},{"year":2020,"finding":"Jumonji Domain Containing 6 (Jmjd6) modifies LIAT1 via its lysyl-hydroxylase activity in a manner requiring the LIAT1 poly-K region, and this modification inhibits LIAT1 nucleolar targeting.","method":"Immunocytochemistry, bimolecular fluorescence complementation, Jmjd6 inhibitor/knockout experiments","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — post-translational modification identified with functional consequence (loss of nucleolar targeting), single lab, multiple orthogonal methods","pmids":["33443146"],"is_preprint":false},{"year":2024,"finding":"Recombinant mouse LIAT1 directly binds human tRNA-Arg in vitro, identifying LIAT1 as an RNA-binding protein.","method":"In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg","journal":"microPublication biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single in vitro binding assay, single lab, no mutagenesis or functional consequence demonstrated","pmids":["39081859"],"is_preprint":false}],"current_model":"LIAT1 is an intrinsically disordered protein that binds and stimulates the arginyltransferase Ate1 (component of the Arg/N-degron pathway) via a conserved ~30-residue domain, localizes to the nucleolus through a poly-K IDR region to participate in liquid-liquid phase separation, is post-translationally modified by Jmjd6 lysyl-hydroxylase activity which inhibits its nucleolar targeting, and can bind tRNA-Arg in vitro suggesting an RNA-binding capacity."},"narrative":{"mechanistic_narrative":"LIAT1 (Ligand of Ate1) is an intrinsically disordered protein that functions as a positive regulator of the Arg/N-degron pathway by directly binding the arginyltransferase Ate1 and stimulating its N-terminal arginylation activity [PMID:25369936]. Binding occurs through a conserved ~30-residue region of LIAT1 and shows preference for specific Ate1 isoforms [PMID:25369936]. Its N-terminal half is an intrinsically disordered region containing a low-complexity poly-K segment that targets LIAT1 to the nucleolus and supports liquid-liquid phase separation there [PMID:33443146]. Nucleolar targeting is controlled by Jmjd6, whose lysyl-hydroxylase activity modifies LIAT1 in a poly-K-dependent manner and inhibits its nucleolar localization [PMID:33443146]. Beyond these activities and an in vitro capacity to bind tRNA-Arg [PMID:39081859], no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established LIAT1's defining molecular partnership by showing it directly binds the arginyltransferase Ate1 through a discrete conserved region, defining LIAT1 as an Ate1-interacting factor.","evidence":"Binding assays with isoform-specific affinity measurement and deletion/domain mapping","pmids":["25369936"],"confidence":"Medium","gaps":["Structural basis of the Ate1 interaction unresolved","Functional consequence of isoform preference in cells not established"]},{"year":2014,"claim":"Answered whether LIAT1 merely binds or actively modulates Ate1 by demonstrating it stimulates arginylation, placing LIAT1 as a positive regulator of the Arg/N-degron pathway.","evidence":"In vitro arginylation assay on a model substrate","pmids":["25369936"],"confidence":"Medium","gaps":["No endogenous substrate dependence shown in cells","Mechanism of stimulation (allosteric vs substrate presentation) unknown"]},{"year":2020,"claim":"Defined the subcellular logic of LIAT1 by mapping its IDR poly-K region as a nucleolar-targeting and phase-separation determinant, linking it to nucleolar condensate biology.","evidence":"BiFC, immunocytochemistry, and domain deletion analysis","pmids":["33443146"],"confidence":"Medium","gaps":["Functional role of LIAT1 within the nucleolus not defined","Relationship between nucleolar LLPS and Ate1 regulation unclear"]},{"year":2020,"claim":"Identified a regulatory input controlling LIAT1 localization by showing Jmjd6 lysyl-hydroxylation of the poly-K region inhibits nucleolar targeting.","evidence":"Immunocytochemistry, BiFC, and Jmjd6 inhibitor/knockout experiments","pmids":["33443146"],"confidence":"Medium","gaps":["Specific hydroxylated residues not mapped","Physiological trigger for Jmjd6 modification of LIAT1 unknown"]},{"year":2024,"claim":"Raised an RNA-binding dimension for LIAT1 by demonstrating in vitro binding to tRNA-Arg.","evidence":"In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg","pmids":["39081859"],"confidence":"Low","gaps":["Single in vitro binding assay without mutagenesis or functional consequence","Specificity versus other tRNAs not established","Connection to arginylation (tRNA-Arg is the arginyl donor) not tested"]},{"year":null,"claim":"The integrated cellular function of LIAT1 — how Ate1 stimulation, nucleolar phase separation, Jmjd6 regulation, and tRNA-Arg binding combine into one physiological role — remains unresolved.","evidence":"No discovery in the corpus connects these activities in a single mechanistic or phenotypic model","pmids":[],"confidence":"Low","gaps":["No organismal or knockout phenotype reported","No endogenous arginylation substrate linked to LIAT1","Whether nucleolar LIAT1 and Ate1-regulatory LIAT1 are the same functional pool is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[2,3]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1]}],"complexes":[],"partners":["ATE1","JMJD6"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ZQX7","full_name":"Protein LIAT1","aliases":["Ligand of ATE1 protein"],"length_aa":453,"mass_kda":49.7,"function":"Participates in nucleolar liquid-liquid phase separation (LLPS) through its N-terminal intrinsically disordered region (IDR). May be involved in ATE1-mediated N-terminal arginylation","subcellular_location":"Nucleus, nucleolus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q6ZQX7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LIAT1","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":[],"url":"https://opencell.sf.czbiohub.org/search/LIAT1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"C17ORF97","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":55.1}],"url":"https://www.proteinatlas.org/search/C17ORF97"},"hgnc":{"alias_symbol":["LOC400566"],"prev_symbol":["C17orf97"]},"alphafold":{"accession":"Q6ZQX7","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZQX7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZQX7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZQX7-F1-predicted_aligned_error_v6.png","plddt_mean":46.41},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LIAT1","jax_strain_url":"https://www.jax.org/strain/search?query=LIAT1"},"sequence":{"accession":"Q6ZQX7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZQX7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZQX7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZQX7"}},"corpus_meta":[{"pmid":"25369936","id":"PMC_25369936","title":"Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25369936","citation_count":20,"is_preprint":false},{"pmid":"33443146","id":"PMC_33443146","title":"The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/33443146","citation_count":6,"is_preprint":false},{"pmid":"39081859","id":"PMC_39081859","title":"tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1.","date":"2024","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/39081859","citation_count":3,"is_preprint":false},{"pmid":"28865488","id":"PMC_28865488","title":"Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study.","date":"2017","source":"Human genomics","url":"https://pubmed.ncbi.nlm.nih.gov/28865488","citation_count":3,"is_preprint":false},{"pmid":"39897169","id":"PMC_39897169","title":"Erratum: Corrigendum: tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1.","date":"2025","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/39897169","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4505,"output_tokens":1108,"usd":0.015067,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7671,"output_tokens":1886,"usd":0.042752,"stage2_stop_reason":"end_turn"},"total_usd":0.057819,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"LIAT1 (Ligand of Ate1) directly binds the arginyltransferase Ate1, with higher affinity for Ate1 isoforms 1A7A and 1B7A; a conserved ~30-residue region of LIAT1 is required for this binding.\",\n      \"method\": \"Protein interaction studies (binding assays), isoform-specific affinity measurements, deletion/domain mapping\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding demonstrated with domain mapping and isoform specificity, single lab, multiple methods reported\",\n      \"pmids\": [\"25369936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"LIAT1 stimulates the in vitro N-terminal arginylation of a model substrate by Ate1, indicating a positive regulatory role in the N-end rule/Arg/N-degron pathway.\",\n      \"method\": \"In vitro arginylation assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro enzymatic assay, single lab, single method\",\n      \"pmids\": [\"25369936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"LIAT1's N-terminal half is an intrinsically disordered region (IDR) containing a low-complexity poly-K region that targets LIAT1 to the nucleolus and facilitates liquid-liquid phase separation (LLPS) there.\",\n      \"method\": \"Bimolecular fluorescence complementation, immunocytochemistry, domain deletion analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiments with functional domain mapping, single lab, two orthogonal methods\",\n      \"pmids\": [\"33443146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Jumonji Domain Containing 6 (Jmjd6) modifies LIAT1 via its lysyl-hydroxylase activity in a manner requiring the LIAT1 poly-K region, and this modification inhibits LIAT1 nucleolar targeting.\",\n      \"method\": \"Immunocytochemistry, bimolecular fluorescence complementation, Jmjd6 inhibitor/knockout experiments\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — post-translational modification identified with functional consequence (loss of nucleolar targeting), single lab, multiple orthogonal methods\",\n      \"pmids\": [\"33443146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Recombinant mouse LIAT1 directly binds human tRNA-Arg in vitro, identifying LIAT1 as an RNA-binding protein.\",\n      \"method\": \"In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single in vitro binding assay, single lab, no mutagenesis or functional consequence demonstrated\",\n      \"pmids\": [\"39081859\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LIAT1 is an intrinsically disordered protein that binds and stimulates the arginyltransferase Ate1 (component of the Arg/N-degron pathway) via a conserved ~30-residue domain, localizes to the nucleolus through a poly-K IDR region to participate in liquid-liquid phase separation, is post-translationally modified by Jmjd6 lysyl-hydroxylase activity which inhibits its nucleolar targeting, and can bind tRNA-Arg in vitro suggesting an RNA-binding capacity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LIAT1 (Ligand of Ate1) is an intrinsically disordered protein that functions as a positive regulator of the Arg/N-degron pathway by directly binding the arginyltransferase Ate1 and stimulating its N-terminal arginylation activity [#0, #1]. Binding occurs through a conserved ~30-residue region of LIAT1 and shows preference for specific Ate1 isoforms [#0]. Its N-terminal half is an intrinsically disordered region containing a low-complexity poly-K segment that targets LIAT1 to the nucleolus and supports liquid-liquid phase separation there [#2]. Nucleolar targeting is controlled by Jmjd6, whose lysyl-hydroxylase activity modifies LIAT1 in a poly-K-dependent manner and inhibits its nucleolar localization [#3]. Beyond these activities and an in vitro capacity to bind tRNA-Arg [#4], no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established LIAT1's defining molecular partnership by showing it directly binds the arginyltransferase Ate1 through a discrete conserved region, defining LIAT1 as an Ate1-interacting factor.\",\n      \"evidence\": \"Binding assays with isoform-specific affinity measurement and deletion/domain mapping\",\n      \"pmids\": [\"25369936\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the Ate1 interaction unresolved\", \"Functional consequence of isoform preference in cells not established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Answered whether LIAT1 merely binds or actively modulates Ate1 by demonstrating it stimulates arginylation, placing LIAT1 as a positive regulator of the Arg/N-degron pathway.\",\n      \"evidence\": \"In vitro arginylation assay on a model substrate\",\n      \"pmids\": [\"25369936\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No endogenous substrate dependence shown in cells\", \"Mechanism of stimulation (allosteric vs substrate presentation) unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined the subcellular logic of LIAT1 by mapping its IDR poly-K region as a nucleolar-targeting and phase-separation determinant, linking it to nucleolar condensate biology.\",\n      \"evidence\": \"BiFC, immunocytochemistry, and domain deletion analysis\",\n      \"pmids\": [\"33443146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role of LIAT1 within the nucleolus not defined\", \"Relationship between nucleolar LLPS and Ate1 regulation unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a regulatory input controlling LIAT1 localization by showing Jmjd6 lysyl-hydroxylation of the poly-K region inhibits nucleolar targeting.\",\n      \"evidence\": \"Immunocytochemistry, BiFC, and Jmjd6 inhibitor/knockout experiments\",\n      \"pmids\": [\"33443146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific hydroxylated residues not mapped\", \"Physiological trigger for Jmjd6 modification of LIAT1 unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Raised an RNA-binding dimension for LIAT1 by demonstrating in vitro binding to tRNA-Arg.\",\n      \"evidence\": \"In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg\",\n      \"pmids\": [\"39081859\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single in vitro binding assay without mutagenesis or functional consequence\", \"Specificity versus other tRNAs not established\", \"Connection to arginylation (tRNA-Arg is the arginyl donor) not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The integrated cellular function of LIAT1 — how Ate1 stimulation, nucleolar phase separation, Jmjd6 regulation, and tRNA-Arg binding combine into one physiological role — remains unresolved.\",\n      \"evidence\": \"No discovery in the corpus connects these activities in a single mechanistic or phenotypic model\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No organismal or knockout phenotype reported\", \"No endogenous arginylation substrate linked to LIAT1\", \"Whether nucleolar LIAT1 and Ate1-regulatory LIAT1 are the same functional pool is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ATE1\", \"JMJD6\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}