Function: 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. Ref.11 Ref.13 Ref.15 Ref.16 Ref.22 Ref.25 Ref.26
Subunit structure: Heterotetramer of two type I and two type II keratins. KRT18 associates with KRT8. Interacts with the thrombin-antithrombin complex
By similarity. Interacts with PNN, HCV core protein and mutated CFTR. Interacts with YWHAE, YWHAH and YWHAZ only when phosphorylated. Interacts with DNAJB6, TCHP and TRADD. Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22 Ref.23
Subcellular location: Cytoplasm › perinuclear region. Nucleus › nucleolus Ref.22 Ref.25 Ref.35.
Tissue specificity: Expressed in colon, placenta, liver and very weakly in exocervix. Increased expression observed in lymph nodes of breast carcinoma. Ref.1 Ref.7 Ref.8 Ref.26
Induction: By IL6/interleukin-6. Ref.26
Post-translational modification: Phosphorylation at Ser-34 increases during mitosis. Hyperphosphorylated at Ser-53 in diseased cirrhosis liver. Phosphorylation increases by IL-6. Ref.11 Ref.14 Ref.16 Ref.21 Ref.25 Ref.26Proteolytically cleaved by caspases during epithelial cell apoptosis. Cleavage occurs at Asp-238 by either caspase-3, caspase-6 or caspase-7. Ref.15O-GlcNAcylation increases solubility, and decreases stability by inducing proteasomal degradation.
Involvement in disease: Cirrhosis (CIRRH) [MIM:215600]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36 Ref.37
Miscellaneous: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Sequence similarities: Belongs to the intermediate filament family.
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