KRT18
Function
Required for the formation of KRT8/KRT18 filaments that are involved in ARHGEF40-mediated actin stress fiber formation and tensional force-induced stress fiber formation and reinforcement (PubMed:26823019). Also acts downstream of ROCK kinase activation as part of a positive feedback mechanism in response to cellular mechanical stress loading (PubMed:26823019). Organization and orientation of KRT18 filaments are responsible for the properly elongated morphology of epithelial tubules (By similarity). Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection.
Involvement in disease
Cirrhosis
CIRRH
A liver disease characterized by severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, and marked deposits of copper. Clinical features include abdomen swelling, jaundice and pulmonary hypertension.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-34 increases during mitosis. Hyperphosphorylated at Ser-53 in diseased cirrhosis liver. Phosphorylation increases by IL-6.
Proteolytically cleaved by caspases during epithelial cell apoptosis. Cleavage occurs at Asp-238 by either caspase-3, caspase-6 or caspase-7.
O-GlcNAcylation increases solubility, and decreases stability by inducing proteasomal degradation.
Sequence Similarities
Belongs to the intermediate filament family.
Tissue Specificity
Expressed in colon, placenta, liver and very weakly in exocervix. Increased expression observed in lymph nodes of breast carcinoma.
Cellular localization
- Nucleus matrix
- Cytoplasm
- Perinuclear region
- Nucleus
- Nucleolus
- Cytoplasm
Alternative names
CYK18, PIG46, KRT18, Cell proliferation-inducing gene 46 protein, Cytokeratin-18, Keratin-18, CK-18, K18
Database links
swissprot:P05783 entrezGene:51350 entrezGene:3852 entrezGene:374454 entrezGene:3875 entrezGene:3853 swissprot:Q7Z794 swissprot:Q01546 swissprot:P13647 swissprot:P02538 omim:148070 omim:148040