{"gene":"KRT36","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2023,"finding":"KRT36 is a substrate of the E3 ubiquitin ligase RNF187; RNF187 interacts with KRT36 and promotes its degradation via lysine 48-linked polyubiquitination, thereby promoting proliferation and migration of spermatogonia (GC-1 cells). Overexpression of KRT36 attenuated the pro-proliferative effect of RNF187 overexpression.","method":"Co-immunoprecipitation, mass spectrometry, overexpression/knockdown in GC-1 cells with proliferation/migration/apoptosis readouts","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus MS identification of interaction, functional rescue experiment with KRT36 overexpression, single lab","pmids":["37738023"],"is_preprint":false},{"year":2020,"finding":"K36 protein localizes specifically to the filiform papillae of the normal tongue dorsal surface, nail beds, Hassall's corpuscles in the thymus, and the hair cortex, but is absent from squamous epithelia of skin, cervix, and oesophagus, as determined by immunohistochemistry with affinity-purified polyclonal antibodies. K36 is not expressed in tongue squamous cell carcinoma samples.","method":"Immunohistochemistry with affinity-purified polyclonal antibody across a panel of normal and cancer tissues","journal":"Molecular and clinical oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct protein localization by IHC across multiple tissue types with validated antibody, single lab, no functional consequence established","pmids":["32257198"],"is_preprint":false},{"year":2011,"finding":"In sheep, KRT36 mRNA expression is restricted to the cortex compartment of the wool/hair fibre, as determined by transcript profiling of distinct fibre compartments.","method":"cDNA sequencing and compartment-specific transcript expression analysis in sheep fibre follicles","journal":"Experimental dermatology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (transcript profiling), ortholog (sheep), localization only without functional consequence","pmids":["21554405"],"is_preprint":false}],"current_model":"KRT36 is a type I hair keratin expressed in the hair cortex, tongue filiform papillae, nail beds, and thymus Hassall's corpuscles; it acts as a substrate of the E3 ubiquitin ligase RNF187, which targets KRT36 for lysine 48-linked polyubiquitination and proteasomal degradation to promote spermatogonial cell proliferation and migration."},"narrative":{"mechanistic_narrative":"KRT36 is a type I hair keratin whose expression is anatomically restricted, with protein detected in the hair cortex, tongue filiform papillae, nail beds, and thymic Hassall's corpuscles, while being absent from squamous epithelia of skin, cervix, and oesophagus and from tongue squamous cell carcinoma [PMID:32257198]. This cortex-restricted expression pattern is conserved, as the KRT36 transcript is confined to the cortex compartment of the wool/hair fibre in sheep [PMID:21554405]. Beyond its role as a structural keratin, KRT36 is a substrate of the E3 ubiquitin ligase RNF187, which binds KRT36 and targets it for lysine 48-linked polyubiquitination and proteasomal degradation; this turnover promotes proliferation and migration of spermatogonia, and KRT36 overexpression counteracts the pro-proliferative effect of RNF187 [PMID:37738023]. No further mechanistic detail on KRT36's filament-assembly or other functions has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Established where KRT36 is expressed within the hair/wool fibre, defining it as a compartment-specific cortical keratin rather than a broadly expressed one.","evidence":"Compartment-specific transcript profiling of sheep fibre follicles","pmids":["21554405"],"confidence":"Low","gaps":["Ortholog (sheep) and transcript-only, no protein-level confirmation in human","No functional consequence of cortical restriction established","Single method, single lab"]},{"year":2020,"claim":"Resolved the human protein-level tissue distribution of K36, showing restriction to specialized keratinized structures and loss in tongue carcinoma, suggesting a marker value for normal differentiation.","evidence":"Immunohistochemistry with affinity-purified polyclonal antibody across normal and cancer tissue panels","pmids":["32257198"],"confidence":"Medium","gaps":["No functional role demonstrated","Mechanistic basis of loss in carcinoma not addressed","Single lab"]},{"year":2023,"claim":"Identified the first regulatory mechanism controlling KRT36 abundance and linked it to a non-structural cellular role, showing KRT36 is degraded by RNF187 to enable spermatogonial proliferation and migration.","evidence":"Reciprocal Co-IP plus mass spectrometry and overexpression/knockdown rescue in GC-1 cells with proliferation/migration/apoptosis readouts","pmids":["37738023"],"confidence":"Medium","gaps":["Single lab, not independently confirmed","Direct ubiquitination site on KRT36 not mapped","Mechanism by which KRT36 restrains proliferation downstream is unknown"]},{"year":null,"claim":"Whether KRT36 has a canonical intermediate-filament structural function and how its degradation by RNF187 connects to its restricted expression pattern remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No filament-assembly or partner type II keratin identified in the corpus","Physiological significance of KRT36 turnover beyond cell-line models unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RNF187"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O76013","full_name":"Keratin, type I cuticular Ha6","aliases":["Hair keratin, type I Ha6","Keratin-36","K36"],"length_aa":467,"mass_kda":52.2,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O76013/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KRT36","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KRT36","total_profiled":1310},"omim":[{"mim_id":"604540","title":"KERATIN 36, TYPE I; KRT36","url":"https://www.omim.org/entry/604540"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":3.1},{"tissue":"skin 1","ntpm":1.7}],"url":"https://www.proteinatlas.org/search/KRT36"},"hgnc":{"alias_symbol":[],"prev_symbol":["KRTHA6"]},"alphafold":{"accession":"O76013","domains":[{"cath_id":"1.10.287","chopping":"94-136","consensus_level":"medium","plddt":87.9867,"start":94,"end":136}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O76013","model_url":"https://alphafold.ebi.ac.uk/files/AF-O76013-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O76013-F1-predicted_aligned_error_v6.png","plddt_mean":75.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KRT36","jax_strain_url":"https://www.jax.org/strain/search?query=KRT36"},"sequence":{"accession":"O76013","fasta_url":"https://rest.uniprot.org/uniprotkb/O76013.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O76013/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O76013"}},"corpus_meta":[{"pmid":"21554405","id":"PMC_21554405","title":"Annotation of sheep keratin intermediate filament genes and their patterns of expression.","date":"2011","source":"Experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/21554405","citation_count":61,"is_preprint":false},{"pmid":"29103286","id":"PMC_29103286","title":"Association analysis of polymorphisms in six keratin genes with wool traits in sheep.","date":"2017","source":"Asian-Australasian journal of animal sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29103286","citation_count":21,"is_preprint":false},{"pmid":"35864447","id":"PMC_35864447","title":"Effect of the FA2H Gene on cashmere fineness of Jiangnan cashmere goats based on transcriptome sequencing.","date":"2022","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35864447","citation_count":16,"is_preprint":false},{"pmid":"37738023","id":"PMC_37738023","title":"E3 ubiquitin ligase RNF187 promotes growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84.","date":"2023","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/37738023","citation_count":15,"is_preprint":false},{"pmid":"32257198","id":"PMC_32257198","title":"Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue.","date":"2020","source":"Molecular and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32257198","citation_count":5,"is_preprint":false},{"pmid":"39931245","id":"PMC_39931245","title":"The immunological landscape of CCL26High invasive oral squamous cell carcinoma.","date":"2025","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/39931245","citation_count":4,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.13.670025","title":"Differential transcriptomics and metabolomics analyses of the skin of coarse and fine Liaoning cashmere goats","date":"2025-08-15","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.13.670025","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5861,"output_tokens":782,"usd":0.014656,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7199,"output_tokens":1288,"usd":0.034098,"stage2_stop_reason":"end_turn"},"total_usd":0.048754,"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\": 2023,\n      \"finding\": \"KRT36 is a substrate of the E3 ubiquitin ligase RNF187; RNF187 interacts with KRT36 and promotes its degradation via lysine 48-linked polyubiquitination, thereby promoting proliferation and migration of spermatogonia (GC-1 cells). Overexpression of KRT36 attenuated the pro-proliferative effect of RNF187 overexpression.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, overexpression/knockdown in GC-1 cells with proliferation/migration/apoptosis readouts\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus MS identification of interaction, functional rescue experiment with KRT36 overexpression, single lab\",\n      \"pmids\": [\"37738023\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"K36 protein localizes specifically to the filiform papillae of the normal tongue dorsal surface, nail beds, Hassall's corpuscles in the thymus, and the hair cortex, but is absent from squamous epithelia of skin, cervix, and oesophagus, as determined by immunohistochemistry with affinity-purified polyclonal antibodies. K36 is not expressed in tongue squamous cell carcinoma samples.\",\n      \"method\": \"Immunohistochemistry with affinity-purified polyclonal antibody across a panel of normal and cancer tissues\",\n      \"journal\": \"Molecular and clinical oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct protein localization by IHC across multiple tissue types with validated antibody, single lab, no functional consequence established\",\n      \"pmids\": [\"32257198\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In sheep, KRT36 mRNA expression is restricted to the cortex compartment of the wool/hair fibre, as determined by transcript profiling of distinct fibre compartments.\",\n      \"method\": \"cDNA sequencing and compartment-specific transcript expression analysis in sheep fibre follicles\",\n      \"journal\": \"Experimental dermatology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (transcript profiling), ortholog (sheep), localization only without functional consequence\",\n      \"pmids\": [\"21554405\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KRT36 is a type I hair keratin expressed in the hair cortex, tongue filiform papillae, nail beds, and thymus Hassall's corpuscles; it acts as a substrate of the E3 ubiquitin ligase RNF187, which targets KRT36 for lysine 48-linked polyubiquitination and proteasomal degradation to promote spermatogonial cell proliferation and migration.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KRT36 is a type I hair keratin whose expression is anatomically restricted, with protein detected in the hair cortex, tongue filiform papillae, nail beds, and thymic Hassall's corpuscles, while being absent from squamous epithelia of skin, cervix, and oesophagus and from tongue squamous cell carcinoma [#1]. This cortex-restricted expression pattern is conserved, as the KRT36 transcript is confined to the cortex compartment of the wool/hair fibre in sheep [#2]. Beyond its role as a structural keratin, KRT36 is a substrate of the E3 ubiquitin ligase RNF187, which binds KRT36 and targets it for lysine 48-linked polyubiquitination and proteasomal degradation; this turnover promotes proliferation and migration of spermatogonia, and KRT36 overexpression counteracts the pro-proliferative effect of RNF187 [#0]. No further mechanistic detail on KRT36's filament-assembly or other functions has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established where KRT36 is expressed within the hair/wool fibre, defining it as a compartment-specific cortical keratin rather than a broadly expressed one.\",\n      \"evidence\": \"Compartment-specific transcript profiling of sheep fibre follicles\",\n      \"pmids\": [\"21554405\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Ortholog (sheep) and transcript-only, no protein-level confirmation in human\", \"No functional consequence of cortical restriction established\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved the human protein-level tissue distribution of K36, showing restriction to specialized keratinized structures and loss in tongue carcinoma, suggesting a marker value for normal differentiation.\",\n      \"evidence\": \"Immunohistochemistry with affinity-purified polyclonal antibody across normal and cancer tissue panels\",\n      \"pmids\": [\"32257198\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional role demonstrated\", \"Mechanistic basis of loss in carcinoma not addressed\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified the first regulatory mechanism controlling KRT36 abundance and linked it to a non-structural cellular role, showing KRT36 is degraded by RNF187 to enable spermatogonial proliferation and migration.\",\n      \"evidence\": \"Reciprocal Co-IP plus mass spectrometry and overexpression/knockdown rescue in GC-1 cells with proliferation/migration/apoptosis readouts\",\n      \"pmids\": [\"37738023\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, not independently confirmed\", \"Direct ubiquitination site on KRT36 not mapped\", \"Mechanism by which KRT36 restrains proliferation downstream is unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether KRT36 has a canonical intermediate-filament structural function and how its degradation by RNF187 connects to its restricted expression pattern remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No filament-assembly or partner type II keratin identified in the corpus\", \"Physiological significance of KRT36 turnover beyond cell-line models unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"RNF187\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}