{"id":"8da91a45-c450-50a5-97e3-7f713d685135","stable_key":"f2ec2007-88ff-5a96-a73b-8b5085e9cea9:mbz-more-than-one-isotype","predicate":"modulates","statement":"Three beta-tubulin cDNAs were cloned from Haemonchus contortus, two differing at only 23 nucleotides giving 4 amino acid changes and a third representing a different isotype class differing extensively in the carboxy terminus; comparison with mammalian beta-tubulins identified several regions of consistent difference whose functional significance has not been defined, and sequences very similar or identical to two of the clones were present in both benzimidazole-sensitive and benzimidazole-resistant populations although resistant organisms may differ in the presence of a gene product related to the third.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1cf417b1-5820-51c4-a3a6-e8a082b2a092","mechanism_event_label":"The worm has several versions of this protein, and the differences from ours are known but not explained.","subject":{"id":"bd64884e-6ee7-55df-9993-c2887f5a50df","slug":"nematode-beta-tubulin","display_name":"Nematode beta-tubulin","entity_type_key":"protein"},"object":{"id":"de0d4926-764b-531e-8fb9-961449221d21","slug":"benzimidazole-resistance","display_name":"Resistance to benzimidazole anthelmintics","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1cf417b1-5820-51c4-a3a6-e8a082b2a092","stable_key":"f2ec2007-88ff-5a96-a73b-8b5085e9cea9:mbz-more-than-one-isotype-event","event_type":"observed_intervention","label":"The worm has several versions of this protein, and the differences from ours are known but not explained.","description":"Three beta-tubulin cDNAs were cloned from Haemonchus contortus, two differing at only 23 nucleotides giving 4 amino acid changes and a third representing a different isotype class differing extensively in the carboxy terminus; comparison with mammalian beta-tubulins identified several regions of consistent difference whose functional significance has not been defined, and sequences very similar or identical to two of the clones were present in both benzimidazole-sensitive and benzimidazole-resistant populations although resistant organisms may differ in the presence of a gene product related to the third.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3394b04b-6dc0-528b-8e94-0644d5d33f45","slug":"mammalian-brain-tubulin","display_name":"Mammalian brain tubulin","entity_type_key":"protein"},"role":"compared_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bd64884e-6ee7-55df-9993-c2887f5a50df","slug":"nematode-beta-tubulin","display_name":"Nematode beta-tubulin","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"de0d4926-764b-531e-8fb9-961449221d21","slug":"benzimidazole-resistance","display_name":"Resistance to benzimidazole anthelmintics","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mebendazole-research/1741017.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c\", \"start_char\": 0, \"end_char\": 1425, \"text_sha256\": \"5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cloning and sequencing of three beta-tubulin cDNAs from Haemonchus contortus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sequence comparison across nematode and mammalian beta-tubulins and across sensitive and resistant populations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Sequence work only. It states plainly that the molecular basis of the nematode versus mammalian difference is not known, which is still the open question in this chapter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms.","comparator":null,"unit":null,"notes":"","entity":{"slug":"mebendazole","display_name":"Mebendazole","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Nematode","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The worm has several versions of this protein, and the differences from ours are known but not explained.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mbz-p1741017] Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. (1992). https://pubmed.ncbi.nlm.nih.gov/1741017/ DOI: 10.1016/0166-6851(92)90227-b","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Beta-tubulin genes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"159ee688-f6e7-5563-853f-13f4e41f12b2","evidence_kind":"source_excerpt","locator":"Lines 290-301","start_line":290,"end_line":301,"excerpt":"### mbz-more-than-one-isotype\nThree beta-tubulin cDNAs were cloned from Haemonchus contortus, two differing at only 23 nucleotides giving 4 amino acid changes and a third representing a different isotype class differing extensively in the carboxy terminus; comparison with mammalian beta-tubulins identified several regions of consistent difference whose functional significance has not been defined, and sequences very similar or identical to two of the clones were present in both benzimidazole-sensitive and benzimidazole-resistant populations although resistant organisms may differ in the presence of a gene product related to the third.\nCondition category: normal\nnutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms.\nplain_language: The worm has several versions of this protein, and the differences from ours are known but not explained.\norganism: Nematode\ntissue_or_cell_type: Beta-tubulin genes\nexperimental_model: Cloning and sequencing of three beta-tubulin cDNAs from Haemonchus contortus\nlimitations: Sequence work only. It states plainly that the molecular basis of the nematode versus mammalian difference is not known, which is still the open question in this chapter.\nexposure: Sequence comparison across nematode and mammalian beta-tubulins and across sensitive and resistant populations\nevidence_span: {\"source_cache\": \"artifacts/mebendazole-research/1741017.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c\", \"start_char\": 0, \"end_char\": 1425, \"text_sha256\": \"5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c\"}\n[mbz-p1741017] Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. 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