KRT36

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.

1. 2011 Low

   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

   PMID:21554405

   Open questions at the time

   • Ortholog (sheep) and transcript-only, no protein-level confirmation in human
   • No functional consequence of cortical restriction established
   • Single method, single lab
2. 2020 Medium

   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

   PMID:32257198

   Open questions at the time

   • No functional role demonstrated
   • Mechanistic basis of loss in carcinoma not addressed
   • Single lab
3. 2023 Medium

   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

   PMID:37738023

   Open questions at the time

   • Single lab, not independently confirmed
   • Direct ubiquitination site on KRT36 not mapped
   • Mechanism by which KRT36 restrains proliferation downstream is unknown

• Whether KRT36 has a canonical intermediate-filament structural function and how its degradation by RNF187 connects to its restricted expression pattern remain unresolved.
• No filament-assembly or partner type II keratin identified in the corpus
• Physiological significance of KRT36 turnover beyond cell-line models unknown