{"gene":"TEKTIP1","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2021,"finding":"TEKTIP1 was identified as a novel microtubule inner protein (MIP) located at the center of the tektin bundle within doublet microtubules (DMTs) of mammalian cilia, resolved by cryo-EM of the 48-nm repeat of bovine respiratory cilia DMTs.","method":"Cryo-electron microscopy (cryo-EM) atomic model reconstruction of mammalian doublet microtubules","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM atomic model with high resolution structural validation; highly cited foundational study","pmids":["34715025"],"is_preprint":false},{"year":2024,"finding":"TEKTIP1 is required for male fertility and sperm motility in mice; Tektip1-knockout males are subfertile with reduced sperm motility and disorganized axoneme structures, demonstrating TEKTIP1's physiological role in stabilizing the tektin bundle and axoneme of sperm flagella.","method":"Tektip1-knockout mouse model, sperm motility assays, transmission electron microscopy of axoneme ultrastructure","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 2 — clean KO mouse with defined cellular phenotype (subfertility, reduced motility, axoneme disorganization) replicated with multiple orthogonal methods","pmids":["38448737"],"is_preprint":false},{"year":2024,"finding":"TEKTIP1 preferentially interacts with TEKT3 among tektin family members, and loss of TEKTIP1 disrupts the native status of TEKT3 and impairs TEKT3's interactions with other tektins, indicating TEKTIP1 stabilizes the tektin bundle through its interaction with TEKT3.","method":"Co-immunoprecipitation (Co-IP), loss-of-function analysis in Tektip1-/- mice, assessment of tektin bundle organization","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP binding partner identification combined with KO functional validation in single study","pmids":["38448737"],"is_preprint":false}],"current_model":"TEKTIP1 is a microtubule inner protein (MIP) that localizes at the center of the tektin bundle within doublet microtubules of cilia/flagella, where it stabilizes the tektin bundle by preferentially interacting with TEKT3 and facilitating its association with other tektins, and is required for proper axoneme organization and sperm motility in mice."},"narrative":{"teleology":[{"year":2021,"claim":"Cryo-EM of the 48-nm repeat of mammalian doublet microtubules revealed TEKTIP1 as a previously uncharacterized MIP positioned at the center of the tektin bundle, establishing its structural niche within the axoneme.","evidence":"Cryo-EM atomic model reconstruction of bovine respiratory cilia doublet microtubules","pmids":["34715025"],"confidence":"High","gaps":["No functional data existed at this stage to determine whether TEKTIP1 is required for tektin bundle integrity","Binding partners and interaction surfaces within the bundle were unresolved","Role in motile versus primary cilia was not distinguished"]},{"year":2024,"claim":"Knockout of Tektip1 in mice demonstrated that the protein is required for axoneme organization and sperm motility, and that it stabilizes the tektin bundle through preferential interaction with TEKT3, bridging the structural observation to a physiological function.","evidence":"Tektip1-knockout mouse model with sperm motility assays, TEM of axoneme ultrastructure, and Co-IP of tektin family members","pmids":["38448737"],"confidence":"High","gaps":["TEKTIP1–TEKT3 interaction relies on Co-IP without reciprocal pull-down or structural mapping of the interface","Whether TEKTIP1 functions equivalently in respiratory cilia versus sperm flagella is untested","Mechanism by which TEKTIP1 loss disrupts TEKT3 native status (degradation, misfolding, or mislocalization) is not resolved"]},{"year":null,"claim":"It remains unknown whether TEKTIP1 loss affects motile cilia beyond sperm flagella, what structural determinants mediate its selective binding to TEKT3, and whether TEKTIP1 mutations cause ciliopathies or male infertility in humans.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of the TEKTIP1–TEKT3 interface","No human genetic data linking TEKTIP1 variants to disease","Function in respiratory or other motile cilia not directly tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]}],"complexes":["tektin bundle"],"partners":["TEKT3"],"other_free_text":[]},"mechanistic_narrative":"TEKTIP1 is a microtubule inner protein (MIP) that occupies the center of the tektin bundle within doublet microtubules of cilia and flagella, where it stabilizes bundle architecture by preferentially binding TEKT3 and facilitating TEKT3's association with other tektin family members [PMID:34715025, PMID:38448737]. Loss of TEKTIP1 in mice causes disorganized axoneme ultrastructure, reduced sperm motility, and male subfertility, establishing it as essential for proper flagellar function [PMID:38448737]."},"prefetch_data":{"uniprot":{"accession":"A6NCJ1","full_name":"Tektin bundle-interacting protein 1","aliases":[],"length_aa":209,"mass_kda":24.2,"function":"Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Located at the center of the tektin bundle where may function to recruit tektins or stabilize the bundle","subcellular_location":"Cytoplasm, cytoskeleton, cilium axoneme; Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/A6NCJ1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TEKTIP1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TEKTIP1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Endoplasmic reticulum","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":47.9}],"url":"https://www.proteinatlas.org/search/TEKTIP1"},"hgnc":{"alias_symbol":["LOC100128569"],"prev_symbol":["C19orf71"]},"alphafold":{"accession":"A6NCJ1","domains":[{"cath_id":"-","chopping":"63-121","consensus_level":"medium","plddt":59.9908,"start":63,"end":121}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NCJ1","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6NCJ1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6NCJ1-F1-predicted_aligned_error_v6.png","plddt_mean":41.78},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TEKTIP1","jax_strain_url":"https://www.jax.org/strain/search?query=TEKTIP1"},"sequence":{"accession":"A6NCJ1","fasta_url":"https://rest.uniprot.org/uniprotkb/A6NCJ1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6NCJ1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NCJ1"}},"corpus_meta":[{"pmid":"36945044","id":"PMC_36945044","title":"DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion.","date":"2023","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/36945044","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38448737","id":"PMC_38448737","title":"Tektin bundle interacting protein, TEKTIP1, functions to stabilize the tektin bundle and axoneme in mouse sperm flagella.","date":"2024","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/38448737","citation_count":10,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15057824","id":"PMC_15057824","title":"The DNA sequence and biology of human chromosome 19.","date":"2004","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/15057824","citation_count":271,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34715025","id":"PMC_34715025","title":"De novo identification of mammalian ciliary motility proteins using cryo-EM.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/34715025","citation_count":111,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26760575","id":"PMC_26760575","title":"High-throughput analyses of hnRNP H1 dissects its multi-functional aspect.","date":"2016","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/26760575","citation_count":50,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36138187","id":"PMC_36138187","title":"NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia.","date":"2022","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36138187","citation_count":46,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36543142","id":"PMC_36543142","title":"Pro-prion, as a membrane adaptor protein for E3 ligase c-Cbl, facilitates the ubiquitination of IGF-1R, promoting melanoma metastasis.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/36543142","citation_count":12,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2578,"output_tokens":540,"usd":0.007917},"stage2":{"model":"claude-opus-4-6","input_tokens":3704,"output_tokens":774,"usd":0.056805},"total_usd":0.14615,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":5100,"output_tokens":758,"usd":0.013335},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":4184,"output_tokens":979,"usd":0.068093}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"TEKTIP1 localizes at the center of the tektin bundle within the lumen of doublet microtubules (DMTs) of sperm flagella, as identified by cryo-electron microscopy, and preferentially interacts with TEKT3 among tektin family members.\",\n      \"method\": \"Cryo-EM localization; Co-immunoprecipitation/interaction assays in Tektip1-knockout mice\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — cryo-EM structural localization combined with KO mouse model and binding partner identification using multiple orthogonal methods\",\n      \"pmids\": [\"38448737\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Loss of TEKTIP1 in Tektip1-/- mice disrupts tektin bundle organization primarily by affecting the native conformation of TEKT3 and its interactions with other tektins, leading to disorganized axoneme structures and abnormal flagellar waveforms, resulting in reduced sperm motility and male subfertility.\",\n      \"method\": \"Tektip1-knockout mouse model; sperm motility assays; axoneme structural analysis by electron microscopy; co-immunoprecipitation of tektin interactions\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular and structural phenotype plus molecular pathway placement via interaction studies\",\n      \"pmids\": [\"38448737\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEKTIP1 is a microtubule inner protein that localizes at the center of the tektin bundle within sperm flagellar doublet microtubules, where it stabilizes the bundle by interacting preferentially with TEKT3 and maintaining its proper conformation and association with other tektins, thereby preserving axoneme integrity and sperm motility.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"TEKTIP1 was identified as a novel microtubule inner protein (MIP) located at the center of the tektin bundle within doublet microtubules (DMTs) of mammalian cilia, resolved by cryo-EM of the 48-nm repeat of bovine respiratory cilia DMTs.\",\n      \"method\": \"Cryo-electron microscopy (cryo-EM) atomic model reconstruction of mammalian doublet microtubules\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM atomic model with high resolution structural validation; highly cited foundational study\",\n      \"pmids\": [\"34715025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TEKTIP1 is required for male fertility and sperm motility in mice; Tektip1-knockout males are subfertile with reduced sperm motility and disorganized axoneme structures, demonstrating TEKTIP1's physiological role in stabilizing the tektin bundle and axoneme of sperm flagella.\",\n      \"method\": \"Tektip1-knockout mouse model, sperm motility assays, transmission electron microscopy of axoneme ultrastructure\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO mouse with defined cellular phenotype (subfertility, reduced motility, axoneme disorganization) replicated with multiple orthogonal methods\",\n      \"pmids\": [\"38448737\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TEKTIP1 preferentially interacts with TEKT3 among tektin family members, and loss of TEKTIP1 disrupts the native status of TEKT3 and impairs TEKT3's interactions with other tektins, indicating TEKTIP1 stabilizes the tektin bundle through its interaction with TEKT3.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP), loss-of-function analysis in Tektip1-/- mice, assessment of tektin bundle organization\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP binding partner identification combined with KO functional validation in single study\",\n      \"pmids\": [\"38448737\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEKTIP1 is a microtubule inner protein (MIP) that localizes at the center of the tektin bundle within doublet microtubules of cilia/flagella, where it stabilizes the tektin bundle by preferentially interacting with TEKT3 and facilitating its association with other tektins, and is required for proper axoneme organization and sperm motility in mice.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TEKTIP1 is a microtubule inner protein that localizes at the center of the tektin bundle within the lumen of sperm flagellar doublet microtubules, where it preferentially interacts with TEKT3 to stabilize the tektin bundle [PMID:38448737]. Loss of TEKTIP1 disrupts the native conformation of TEKT3 and its interactions with other tektins, leading to disorganized axoneme structures, abnormal flagellar waveforms, reduced sperm motility, and male subfertility [PMID:38448737].\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Cryo-EM and knockout mouse studies together established that TEKTIP1 resides at the core of the tektin bundle in flagellar doublet microtubules, preferentially binds TEKT3, and is required for tektin bundle integrity, normal axoneme architecture, and sperm motility — answering the question of what stabilizes the tektin bundle from within.\",\n      \"evidence\": \"Cryo-EM structural localization in sperm flagella; Tektip1-knockout mouse model with sperm motility assays, axoneme EM, and co-immunoprecipitation\",\n      \"pmids\": [\"38448737\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TEKTIP1 interacts directly with tektins other than TEKT3 or acts exclusively through TEKT3\",\n        \"Structural basis of the TEKTIP1–TEKT3 interaction at atomic resolution\",\n        \"Whether TEKTIP1 functions in cilia of non-sperm cell types\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether TEKTIP1 has roles beyond structural stabilization of the tektin bundle, such as signaling or regulatory functions within the axoneme, and whether its loss contributes to human male infertility.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human genetic studies linking TEKTIP1 mutations to infertility\",\n        \"No biochemical reconstitution of TEKTIP1–tektin bundle assembly in vitro\",\n        \"No data on TEKTIP1 post-translational modifications or regulation\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"tektin bundle\"],\n    \"partners\": [\"TEKT3\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"TEKTIP1 is a microtubule inner protein (MIP) that occupies the center of the tektin bundle within doublet microtubules of cilia and flagella, where it stabilizes bundle architecture by preferentially binding TEKT3 and facilitating TEKT3's association with other tektin family members [PMID:34715025, PMID:38448737]. Loss of TEKTIP1 in mice causes disorganized axoneme ultrastructure, reduced sperm motility, and male subfertility, establishing it as essential for proper flagellar function [PMID:38448737].\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Cryo-EM of the 48-nm repeat of mammalian doublet microtubules revealed TEKTIP1 as a previously uncharacterized MIP positioned at the center of the tektin bundle, establishing its structural niche within the axoneme.\",\n      \"evidence\": \"Cryo-EM atomic model reconstruction of bovine respiratory cilia doublet microtubules\",\n      \"pmids\": [\"34715025\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No functional data existed at this stage to determine whether TEKTIP1 is required for tektin bundle integrity\",\n        \"Binding partners and interaction surfaces within the bundle were unresolved\",\n        \"Role in motile versus primary cilia was not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Knockout of Tektip1 in mice demonstrated that the protein is required for axoneme organization and sperm motility, and that it stabilizes the tektin bundle through preferential interaction with TEKT3, bridging the structural observation to a physiological function.\",\n      \"evidence\": \"Tektip1-knockout mouse model with sperm motility assays, TEM of axoneme ultrastructure, and Co-IP of tektin family members\",\n      \"pmids\": [\"38448737\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"TEKTIP1–TEKT3 interaction relies on Co-IP without reciprocal pull-down or structural mapping of the interface\",\n        \"Whether TEKTIP1 functions equivalently in respiratory cilia versus sperm flagella is untested\",\n        \"Mechanism by which TEKTIP1 loss disrupts TEKT3 native status (degradation, misfolding, or mislocalization) is not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether TEKTIP1 loss affects motile cilia beyond sperm flagella, what structural determinants mediate its selective binding to TEKT3, and whether TEKTIP1 mutations cause ciliopathies or male infertility in humans.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of the TEKTIP1–TEKT3 interface\",\n        \"No human genetic data linking TEKTIP1 variants to disease\",\n        \"Function in respiratory or other motile cilia not directly tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"tektin bundle\"\n    ],\n    \"partners\": [\n      \"TEKT3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}