{"gene":"HAUS5","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2017,"finding":"HAUS5, a component of the Augmin/HAUS complex, is required for localization of the Augmin/HAUS complex to the mitotic spindle; its knockdown causes mitotic arrest, centrosome fragmentation, and loss of Augmin/HAUS complex on the mitotic spindle in glioblastoma stem-like cells (GSCs). Ectopic HAUS5 expression rescued viability defects caused by ZNF131 knockdown, placing HAUS5 downstream of ZNF131 in a pathway regulating centrosome integrity.","method":"shRNA knockdown, ectopic overexpression rescue, epistasis analysis (double knockdown with HAUS2/HAUS4), immunofluorescence of mitotic spindle","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotypes, ectopic expression rescue, and epistasis analysis, all in single lab","pmids":["28596487"],"is_preprint":false},{"year":2017,"finding":"The Drosophila ortholog of HAUS5 (Dgt5) directly binds the γ-TuRC protein Dgp71WD, and this interaction is required for accumulation of γ-TuRC (but not Augmin itself) to the mitotic spindle; cross-linking/mass spectrometry identified distance restraints between Dgt5 and other Augmin subunits defining the interface.","method":"Cross-linking mass spectrometry (XL-MS) of immunoaffinity-purified Drosophila Augmin complex, biochemical binding assays, Drosophila embryo functional validation","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — XL-MS with biochemical validation and in vivo functional test in single study; Drosophila ortholog","pmids":["28351835"],"is_preprint":false}],"current_model":"HAUS5 is a subunit of the hetero-octameric Augmin/HAUS complex that directly binds the γ-tubulin ring complex (γ-TuRC) component Dgp71WD (via its Drosophila ortholog Dgt5), thereby recruiting γ-TuRC to pre-existing spindle microtubules to enable branched microtubule nucleation during mitosis; loss of HAUS5 causes centrosome fragmentation and mitotic arrest, and its expression is transcriptionally regulated by ZNF131."},"narrative":{"mechanistic_narrative":"HAUS5 is a subunit of the Augmin/HAUS complex that functions in mitotic spindle assembly by coupling γ-tubulin-dependent microtubule nucleation to pre-existing spindle microtubules [PMID:28596487, PMID:28351835]. HAUS5 is required for localization of the Augmin/HAUS complex to the mitotic spindle, and its loss causes mitotic arrest and centrosome fragmentation; HAUS5 acts downstream of ZNF131 in maintaining centrosome integrity, as ectopic HAUS5 rescues viability defects caused by ZNF131 knockdown [PMID:28596487]. The Drosophila ortholog Dgt5 directly binds the γ-TuRC component Dgp71WD, an interaction required for accumulation of γ-TuRC—but not Augmin itself—at the spindle, defining HAUS5 as the Augmin element that recruits the γ-TuRC nucleation machinery [PMID:28351835]. Beyond these functions, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Established that HAUS5 is required to target the Augmin/HAUS complex to the mitotic spindle and to maintain centrosome integrity, and placed it within a ZNF131-regulated pathway.","evidence":"shRNA knockdown, ectopic overexpression rescue, and epistasis analysis with immunofluorescence of the mitotic spindle in glioblastoma stem-like cells","pmids":["28596487"],"confidence":"Medium","gaps":["Mechanism by which ZNF131 regulates HAUS5 (transcriptional vs other) not directly demonstrated in this finding","Molecular basis for HAUS5-dependent spindle localization not resolved","Tested in a single cell type and single lab"]},{"year":2017,"claim":"Identified the direct molecular link between Augmin and the nucleation machinery by showing the HAUS5 ortholog Dgt5 binds the γ-TuRC component Dgp71WD to recruit γ-TuRC to the spindle.","evidence":"Cross-linking mass spectrometry of immunoaffinity-purified Drosophila Augmin, biochemical binding assays, and Drosophila embryo functional validation","pmids":["28351835"],"confidence":"Medium","gaps":["Direct binding shown for the Drosophila ortholog, not validated for human HAUS5","No structural model of the Dgt5–Dgp71WD interface beyond XL-MS distance restraints","Whether this interaction underlies branched microtubule nucleation not directly tested here"]},{"year":null,"claim":"How HAUS5 within the human Augmin octamer engages γ-TuRC and is regulated to control branched nucleation in human mitosis remains undefined.","evidence":"No discovery in the corpus directly characterizes human HAUS5–γ-TuRC binding or its structural mechanism","pmids":[],"confidence":"Low","gaps":["No human reconstitution of HAUS5-mediated γ-TuRC recruitment","No high-resolution structure of HAUS5 within the Augmin complex","Direct ZNF131–HAUS5 regulatory mechanism unconfirmed"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1]}],"complexes":["Augmin/HAUS complex"],"partners":["DGP71WD","HAUS2","HAUS4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O94927","full_name":"HAUS augmin-like complex subunit 5","aliases":[],"length_aa":633,"mass_kda":71.7,"function":"Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/O94927/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/HAUS5","classification":"Common Essential","n_dependent_lines":1198,"n_total_lines":1208,"dependency_fraction":0.9917218543046358},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FKBP5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/HAUS5","total_profiled":1310},"omim":[{"mim_id":"613432","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 5; HAUS5","url":"https://www.omim.org/entry/613432"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HAUS5"},"hgnc":{"alias_symbol":["dgt5"],"prev_symbol":["KIAA0841"]},"alphafold":{"accession":"O94927","domains":[{"cath_id":"-","chopping":"4-67","consensus_level":"medium","plddt":71.1861,"start":4,"end":67}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O94927","model_url":"https://alphafold.ebi.ac.uk/files/AF-O94927-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O94927-F1-predicted_aligned_error_v6.png","plddt_mean":76.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HAUS5","jax_strain_url":"https://www.jax.org/strain/search?query=HAUS5"},"sequence":{"accession":"O94927","fasta_url":"https://rest.uniprot.org/uniprotkb/O94927.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O94927/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O94927"}},"corpus_meta":[{"pmid":"7596824","id":"PMC_7596824","title":"Effect of competing self-structure on triplex formation with purine-rich oligodeoxynucleotides containing GA repeats.","date":"1995","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/7596824","citation_count":78,"is_preprint":false},{"pmid":"28351835","id":"PMC_28351835","title":"Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle.","date":"2017","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/28351835","citation_count":22,"is_preprint":false},{"pmid":"28596487","id":"PMC_28596487","title":"ZNF131 suppresses centrosome fragmentation in glioblastoma stem-like cells through regulation of HAUS5.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28596487","citation_count":15,"is_preprint":false},{"pmid":"20201499","id":"PMC_20201499","title":"Structure of the 1,N(2)-etheno-2'-deoxyguanosine lesion in the 3'-G(epsilon dG)T-5' sequence opposite a one-base deletion.","date":"2010","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20201499","citation_count":6,"is_preprint":false},{"pmid":"12744708","id":"PMC_12744708","title":"Ethidium probing of the parallel double- and four-stranded structures formed by the telomeric DNA sequences dG(GT)4G and d(GT)5.","date":"2003","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/12744708","citation_count":5,"is_preprint":false},{"pmid":"38612464","id":"PMC_38612464","title":"SMA20/PMIS2 Is a Rapidly Evolving Sperm Membrane Alloantigen with Possible Species-Divergent Function in Fertilization.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38612464","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5868,"output_tokens":698,"usd":0.014037,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7071,"output_tokens":1403,"usd":0.035215,"stage2_stop_reason":"end_turn"},"total_usd":0.049252,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"HAUS5, a component of the Augmin/HAUS complex, is required for localization of the Augmin/HAUS complex to the mitotic spindle; its knockdown causes mitotic arrest, centrosome fragmentation, and loss of Augmin/HAUS complex on the mitotic spindle in glioblastoma stem-like cells (GSCs). Ectopic HAUS5 expression rescued viability defects caused by ZNF131 knockdown, placing HAUS5 downstream of ZNF131 in a pathway regulating centrosome integrity.\",\n      \"method\": \"shRNA knockdown, ectopic overexpression rescue, epistasis analysis (double knockdown with HAUS2/HAUS4), immunofluorescence of mitotic spindle\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotypes, ectopic expression rescue, and epistasis analysis, all in single lab\",\n      \"pmids\": [\"28596487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The Drosophila ortholog of HAUS5 (Dgt5) directly binds the γ-TuRC protein Dgp71WD, and this interaction is required for accumulation of γ-TuRC (but not Augmin itself) to the mitotic spindle; cross-linking/mass spectrometry identified distance restraints between Dgt5 and other Augmin subunits defining the interface.\",\n      \"method\": \"Cross-linking mass spectrometry (XL-MS) of immunoaffinity-purified Drosophila Augmin complex, biochemical binding assays, Drosophila embryo functional validation\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — XL-MS with biochemical validation and in vivo functional test in single study; Drosophila ortholog\",\n      \"pmids\": [\"28351835\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HAUS5 is a subunit of the hetero-octameric Augmin/HAUS complex that directly binds the γ-tubulin ring complex (γ-TuRC) component Dgp71WD (via its Drosophila ortholog Dgt5), thereby recruiting γ-TuRC to pre-existing spindle microtubules to enable branched microtubule nucleation during mitosis; loss of HAUS5 causes centrosome fragmentation and mitotic arrest, and its expression is transcriptionally regulated by ZNF131.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HAUS5 is a subunit of the Augmin/HAUS complex that functions in mitotic spindle assembly by coupling γ-tubulin-dependent microtubule nucleation to pre-existing spindle microtubules [#0, #1]. HAUS5 is required for localization of the Augmin/HAUS complex to the mitotic spindle, and its loss causes mitotic arrest and centrosome fragmentation; HAUS5 acts downstream of ZNF131 in maintaining centrosome integrity, as ectopic HAUS5 rescues viability defects caused by ZNF131 knockdown [#0]. The Drosophila ortholog Dgt5 directly binds the γ-TuRC component Dgp71WD, an interaction required for accumulation of γ-TuRC—but not Augmin itself—at the spindle, defining HAUS5 as the Augmin element that recruits the γ-TuRC nucleation machinery [#1]. Beyond these functions, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established that HAUS5 is required to target the Augmin/HAUS complex to the mitotic spindle and to maintain centrosome integrity, and placed it within a ZNF131-regulated pathway.\",\n      \"evidence\": \"shRNA knockdown, ectopic overexpression rescue, and epistasis analysis with immunofluorescence of the mitotic spindle in glioblastoma stem-like cells\",\n      \"pmids\": [\"28596487\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which ZNF131 regulates HAUS5 (transcriptional vs other) not directly demonstrated in this finding\",\n        \"Molecular basis for HAUS5-dependent spindle localization not resolved\",\n        \"Tested in a single cell type and single lab\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified the direct molecular link between Augmin and the nucleation machinery by showing the HAUS5 ortholog Dgt5 binds the γ-TuRC component Dgp71WD to recruit γ-TuRC to the spindle.\",\n      \"evidence\": \"Cross-linking mass spectrometry of immunoaffinity-purified Drosophila Augmin, biochemical binding assays, and Drosophila embryo functional validation\",\n      \"pmids\": [\"28351835\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding shown for the Drosophila ortholog, not validated for human HAUS5\",\n        \"No structural model of the Dgt5–Dgp71WD interface beyond XL-MS distance restraints\",\n        \"Whether this interaction underlies branched microtubule nucleation not directly tested here\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How HAUS5 within the human Augmin octamer engages γ-TuRC and is regulated to control branched nucleation in human mitosis remains undefined.\",\n      \"evidence\": \"No discovery in the corpus directly characterizes human HAUS5–γ-TuRC binding or its structural mechanism\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human reconstitution of HAUS5-mediated γ-TuRC recruitment\",\n        \"No high-resolution structure of HAUS5 within the Augmin complex\",\n        \"Direct ZNF131–HAUS5 regulatory mechanism unconfirmed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"Augmin/HAUS complex\"],\n    \"partners\": [\"Dgp71WD\", \"HAUS2\", \"HAUS4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}