keratin, type I cytoskeletal 18; cytokeratin-18; CK-18; keratin-18; K18; cell proliferation-inducing gene 46 protein (KRT18, CYK18, PIG46)

Function

• role in the uptake of thrombin-antithrombin complexes by hepatic cells (putative)
• 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
• phosphorylation at Ser-34 increases during mitosis
• 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
• cytokeratin-18 associates with cytokeratin-8
• interacts with the thrombin- antithrombin complex (putative)
• interacts with PNN, HCV core protein & mutated CFTR
• interacts with YWHAE, YWHAH & YWHAZ only when phosphorylated
• interacts with DNAJB6, TCHP & TRADD

Structure

• O-glycosylated at multiple sites; glycans consist of single N-acetylglucosamine residues
• type 1 cytokeratin
• heterotetramer of 2 type 1 & 2 type 2 keratins
• belongs to the intermediate filament family

Compartment

cytoplasm, perinuclear region

Expression

• expressed in colon, placenta, liver & very weakly in exo-cervix
• induced by IL-6

Pathology

• defects in KRT18 are a cause of cryptogenic cirrhosis
• hyperphosphorylated at Ser-53 in diseased cirrhosis liver
• increased expression observed in lymph nodes of breast carcinoma

More general terms

• cytokeratin, epithelial keratins or soft alpha-keratins
• glycoprotein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3875
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3875
• OMIM: https://mirror.omim.org/entry/148070
• OMIM: https://mirror.omim.org/entry/215600
• UniProt: http://www.uniprot.org/uniprot/P05783.html