{"gene":"NIM1K","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2023,"finding":"Human NIM1K (serine/threonine-protein kinase NIM1) was identified as a prenylated cargo protein of PDE6D; NIM1K localizes inside the primary cilium in a prenylation-dependent manner, and this trafficking is mediated by the ciliopathy protein PDE6D.","method":"Affinity proteomics (PDE6D pulldown/interactome), subcellular localization by imaging, prenylation-dependent localization assay","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2-3 — single study using affinity proteomics and localization experiments with prenylation-dependence validation, but not yet replicated","pmids":["36672247"],"is_preprint":false}],"current_model":"Human NIM1K is a prenylated serine/threonine-protein kinase whose trafficking to the primary cilium is mediated by PDE6D, with ciliary localization dependent on its prenylation; its kinase substrates and signaling role within the cilium remain undefined."},"narrative":{"teleology":[{"year":2023,"claim":"Identifying NIM1K as a prenylated ciliary protein resolved how this kinase reaches its subcellular destination: PDE6D binds NIM1K as a prenylated cargo and is required for its ciliary localization.","evidence":"Affinity proteomics (PDE6D pulldown), ciliary imaging, and prenylation-dependence assays in human cells","pmids":["36672247"],"confidence":"Medium","gaps":["Single study; ciliary localization of NIM1K has not been independently confirmed","No kinase substrates or downstream signaling pathway identified","Functional consequence of NIM1K loss from the cilium is unknown"]},{"year":null,"claim":"The catalytic targets and physiological role of NIM1K kinase activity within the primary cilium remain entirely undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate identified for NIM1K kinase activity","No loss-of-function phenotype reported in any model organism","Relationship to ciliopathy-associated signaling pathways not investigated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["PDE6D"],"other_free_text":[]},"mechanistic_narrative":"NIM1K is a serine/threonine-protein kinase that localizes inside the primary cilium in a prenylation-dependent manner, with its ciliary trafficking mediated by the prenylated-cargo chaperone PDE6D [PMID:36672247]. The kinase substrates and signaling functions of NIM1K within the cilium have not been established."},"prefetch_data":{"uniprot":{"accession":"Q8IY84","full_name":"Serine/threonine-protein kinase NIM1","aliases":["NIM1 serine/threonine-protein kinase"],"length_aa":436,"mass_kda":49.6,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8IY84/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NIM1K","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/NIM1K","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":12.1},{"tissue":"choroid plexus","ntpm":4.2},{"tissue":"pituitary gland","ntpm":6.3},{"tissue":"retina","ntpm":9.5}],"url":"https://www.proteinatlas.org/search/NIM1K"},"hgnc":{"alias_symbol":["MGC42105","NIM1"],"prev_symbol":[]},"alphafold":{"accession":"Q8IY84","domains":[{"cath_id":"3.30.200.20","chopping":"56-152","consensus_level":"high","plddt":91.1576,"start":56,"end":152},{"cath_id":"1.10.510.10","chopping":"157-326","consensus_level":"high","plddt":95.4494,"start":157,"end":326},{"cath_id":"-","chopping":"343-403","consensus_level":"high","plddt":87.9989,"start":343,"end":403}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY84","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY84-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY84-F1-predicted_aligned_error_v6.png","plddt_mean":82.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NIM1K","jax_strain_url":"https://www.jax.org/strain/search?query=NIM1K"},"sequence":{"accession":"Q8IY84","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IY84.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IY84/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY84"}},"corpus_meta":[{"pmid":"12028572","id":"PMC_12028572","title":"Tobacco Rar1, EDS1 and NPR1/NIM1 like genes are required for N-mediated resistance to tobacco mosaic virus.","date":"2002","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12028572","citation_count":781,"is_preprint":false},{"pmid":"10662863","id":"PMC_10662863","title":"The Arabidopsis NPR1/NIM1 protein enhances the DNA binding activity of a subgroup of the TGA family of bZIP transcription factors.","date":"2000","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/10662863","citation_count":367,"is_preprint":false},{"pmid":"9090885","id":"PMC_9090885","title":"The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B.","date":"1997","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/9090885","citation_count":326,"is_preprint":false},{"pmid":"3453113","id":"PMC_3453113","title":"The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis.","date":"1987","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/3453113","citation_count":293,"is_preprint":false},{"pmid":"9925642","id":"PMC_9925642","title":"Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast.","date":"1999","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/9925642","citation_count":275,"is_preprint":false},{"pmid":"11891259","id":"PMC_11891259","title":"Benzothiadiazole-induced priming for potentiated responses to pathogen infection, wounding, and infiltration of water into leaves requires the NPR1/NIM1 gene in Arabidopsis.","date":"2002","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/11891259","citation_count":178,"is_preprint":false},{"pmid":"7681363","id":"PMC_7681363","title":"Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer.","date":"1993","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/7681363","citation_count":164,"is_preprint":false},{"pmid":"8515818","id":"PMC_8515818","title":"Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase.","date":"1993","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/8515818","citation_count":143,"is_preprint":false},{"pmid":"10571880","id":"PMC_10571880","title":"Harpin induces disease resistance in Arabidopsis through the systemic acquired resistance pathway mediated by salicylic acid and the NIM1 gene.","date":"1999","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10571880","citation_count":142,"is_preprint":false},{"pmid":"8515817","id":"PMC_8515817","title":"Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase.","date":"1993","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/8515817","citation_count":140,"is_preprint":false},{"pmid":"11442055","id":"PMC_11442055","title":"NIMIN-1, NIMIN-2 and NIMIN-3, members of a novel family of proteins from Arabidopsis that interact with NPR1/NIM1, a key regulator of systemic acquired resistance in plants.","date":"2001","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11442055","citation_count":91,"is_preprint":false},{"pmid":"2004705","id":"PMC_2004705","title":"Genetic and molecular analysis of cdr1/nim1 in Schizosaccharomyces pombe.","date":"1991","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/2004705","citation_count":90,"is_preprint":false},{"pmid":"12383081","id":"PMC_12383081","title":"Over-expression of TGA5, which encodes a bZIP transcription factor that interacts with NIM1/NPR1, confers SAR-independent resistance in Arabidopsis thaliana to Peronospora parasitica.","date":"2002","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12383081","citation_count":90,"is_preprint":false},{"pmid":"14769857","id":"PMC_14769857","title":"In Candida albicans, the Nim1 kinases Gin4 and Hsl1 negatively regulate pseudohypha formation and Gin4 also controls septin organization.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14769857","citation_count":85,"is_preprint":false},{"pmid":"9843572","id":"PMC_9843572","title":"The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast.","date":"1998","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/9843572","citation_count":84,"is_preprint":false},{"pmid":"11844114","id":"PMC_11844114","title":"Runaway cell death, but not basal disease resistance, in lsd1 is SA- and NIM1/NPR1-dependent.","date":"2002","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11844114","citation_count":77,"is_preprint":false},{"pmid":"11551076","id":"PMC_11551076","title":"NIM1 overexpression in Arabidopsis potentiates plant disease resistance and results in enhanced effectiveness of fungicides.","date":"2001","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/11551076","citation_count":66,"is_preprint":false},{"pmid":"11310731","id":"PMC_11310731","title":"Abnormal callose response phenotype and hypersusceptibility to Peronospoara parasitica in defence-compromised arabidopsis nim1-1 and salicylate hydroxylase-expressing plants.","date":"2001","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/11310731","citation_count":63,"is_preprint":false},{"pmid":"12072475","id":"PMC_12072475","title":"Role of salicylic acid and NIM1/NPR1 in race-specific resistance in arabidopsis.","date":"2002","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12072475","citation_count":55,"is_preprint":false},{"pmid":"16861226","id":"PMC_16861226","title":"Direct phosphorylation and activation of a Nim1-related kinase Gin4 by Elm1 in budding yeast.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16861226","citation_count":51,"is_preprint":false},{"pmid":"8930897","id":"PMC_8930897","title":"Spatial organization of the Nim1-Wee1-Cdc2 mitotic control network in Schizosaccharomyces pombe.","date":"1996","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/8930897","citation_count":33,"is_preprint":false},{"pmid":"9077450","id":"PMC_9077450","title":"Nik1: a Nim1-like protein kinase of S. cerevisiae interacts with the Cdc28 complex and regulates cell cycle progression.","date":"1996","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/9077450","citation_count":32,"is_preprint":false},{"pmid":"22366454","id":"PMC_22366454","title":"CDK regulates septin organization through cell-cycle-dependent phosphorylation of the Nim1-related kinase Gin4.","date":"2012","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/22366454","citation_count":25,"is_preprint":false},{"pmid":"8972180","id":"PMC_8972180","title":"Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe.","date":"1997","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8972180","citation_count":21,"is_preprint":false},{"pmid":"11605963","id":"PMC_11605963","title":"Salicylic acid and NIM1/NPR1-independent gene induction by incompatible Peronospora parasitica in arabidopsis.","date":"2001","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/11605963","citation_count":16,"is_preprint":false},{"pmid":"9854178","id":"PMC_9854178","title":"Interleukin-1alpha regulates G1 cell cycle progression and arrest in thyroid carcinoma cell lines NIM1 and NPA.","date":"1999","source":"The Journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/9854178","citation_count":15,"is_preprint":false},{"pmid":"27231094","id":"PMC_27231094","title":"The Nim1 kinase Gin4 has distinct domains crucial for septin assembly, phospholipid binding and mitotic exit.","date":"2016","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/27231094","citation_count":13,"is_preprint":false},{"pmid":"31644361","id":"PMC_31644361","title":"A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1.","date":"2019","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/31644361","citation_count":10,"is_preprint":false},{"pmid":"36672247","id":"PMC_36672247","title":"PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia.","date":"2023","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/36672247","citation_count":7,"is_preprint":false},{"pmid":"38467927","id":"PMC_38467927","title":"The Vitis yeshanensis U-box E3 ubiquitin ligase VyPUB21 enhances resistance to powdery mildew by targeting degradation of NIM1-interacting (NIMIN) protein.","date":"2024","source":"Plant cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/38467927","citation_count":4,"is_preprint":false},{"pmid":"9552364","id":"PMC_9552364","title":"The fission yeast Nim1/Cdr1 kinase: a link between nutritional state and cell cycle control.","date":"1995","source":"Progress in cell cycle research","url":"https://pubmed.ncbi.nlm.nih.gov/9552364","citation_count":4,"is_preprint":false},{"pmid":"9928955","id":"PMC_9928955","title":"Interaction between the fission yeast nim1/cdr1 protein kinase and a dynamin-related protein.","date":"1999","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/9928955","citation_count":4,"is_preprint":false},{"pmid":"9223439","id":"PMC_9223439","title":"Evidence for a mammalian Nim1-like kinase pathway acting at the G0-1/S transition.","date":"1997","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9223439","citation_count":3,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.07.22.604541","title":"Arabidopsis NIM1-INTERACTING1 (NIMIN1) is a multi-domain protein controlling transition from systemic acquired resistance (SAR) to cell death","date":"2024-07-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.22.604541","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.07.634209","title":"Nim1-related kinases regulate septin organization and cytokinesis by modulating Hof1 at the cell division site","date":"2025-02-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.07.634209","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16822,"output_tokens":630,"usd":0.029958},"stage2":{"model":"claude-opus-4-6","input_tokens":3453,"output_tokens":546,"usd":0.046372},"total_usd":0.07633,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify what gene \"NIM1K\" refers to. Paper [29] is the key paper: \"PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia\" (PMID:36672247) — this describes a human serine/threonine-protein kinase NIM1K that is trafficked to primary cilia via PDE6D in a prenylation-dependent manner.\n\nThe bulk of the corpus describes plant NPR1/NIM1 (defense signaling) or fission/budding yeast Nim1/Cdr1 kinase (mitotic control). These are symbol collisions or orthologs in different contexts. The yeast Nim1/Cdr1 papers describe the founding mitotic kinase that phosphorylates Wee1 — these are orthologs of cell cycle regulators, but NIM1K (the human gene queried) is specifically identified in paper [29] as a ciliary cargo protein, not a mitotic regulator.\n\nPaper [33] (PMID:9223439) describes expression of fission yeast Nim1 in human fibroblasts — this is a yeast protein overexpression experiment in human cells, not characterization of human NIM1K.\n\nOnly paper [29] directly characterizes the human NIM1K protein mechanistically.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"Human NIM1K (serine/threonine-protein kinase NIM1) was identified as a prenylated cargo protein of PDE6D; NIM1K localizes inside the primary cilium in a prenylation-dependent manner, and this trafficking is mediated by the ciliopathy protein PDE6D.\",\n      \"method\": \"Affinity proteomics (PDE6D pulldown/interactome), subcellular localization by imaging, prenylation-dependent localization assay\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — single study using affinity proteomics and localization experiments with prenylation-dependence validation, but not yet replicated\",\n      \"pmids\": [\"36672247\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human NIM1K is a prenylated serine/threonine-protein kinase whose trafficking to the primary cilium is mediated by PDE6D, with ciliary localization dependent on its prenylation; its kinase substrates and signaling role within the cilium remain undefined.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NIM1K is a serine/threonine-protein kinase that localizes inside the primary cilium in a prenylation-dependent manner, with its ciliary trafficking mediated by the prenylated-cargo chaperone PDE6D [PMID:36672247]. The kinase substrates and signaling functions of NIM1K within the cilium have not been established.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying NIM1K as a prenylated ciliary protein resolved how this kinase reaches its subcellular destination: PDE6D binds NIM1K as a prenylated cargo and is required for its ciliary localization.\",\n      \"evidence\": \"Affinity proteomics (PDE6D pulldown), ciliary imaging, and prenylation-dependence assays in human cells\",\n      \"pmids\": [\"36672247\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single study; ciliary localization of NIM1K has not been independently confirmed\",\n        \"No kinase substrates or downstream signaling pathway identified\",\n        \"Functional consequence of NIM1K loss from the cilium is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic targets and physiological role of NIM1K kinase activity within the primary cilium remain entirely undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate identified for NIM1K kinase activity\",\n        \"No loss-of-function phenotype reported in any model organism\",\n        \"Relationship to ciliopathy-associated signaling pathways not investigated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"PDE6D\"],\n    \"other_free_text\": []\n  }\n}\n```"}