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

General

cytokeratin, epithelial keratins or soft alpha-keratins glycoprotein phosphoprotein

Properties

CONFIGURATION: oligomer SIZE: entity length = 430 aa MW = 48 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Head {2-79} acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S7} Thr phosphorylation site {T8} Ser phosphorylation site {S10} Thr phosphorylation site {T11} Tyr phosphorylation site {Y13} Ser phosphorylation site {S15} Ser phosphorylation site {S18} Ser phosphorylation site {S30} Ser glycosylation site {S30} Ser phosphorylation site {S31} Ser glycosylation site {S31} Ser phosphorylation site {S34} Tyr phosphorylation site {Y36} Ser phosphorylation site {S42} Ser glycosylation site {S49} Ser phosphorylation site {S53} Ser phosphorylation site {S60} Necessary for interaction with PNN {70-373} MOTIF: TRADD interaction {77-128} Rod {80-387} MOTIF: Coil 1A {80-115} Linker 1 {116-132} Coil 1B {133-224} Linker 12 {225-248} peptide motif {238-239} DNAJB6 interaction {243-391} MOTIF: Coil 2 {249-387} tryptophan residue {271} Thr phosphorylation site {T302} tyrosine residue {331} Tail {388-430} MOTIF: Ser phosphorylation site {S399} Ser phosphorylation site {S401} Thr phosphorylation site {T404}

Database Correlations

OMIM correlations MORBIDMAP 148070 UniProt P05783 Pfam PF00038 Entrez Gene 3875 Kegg hsa:3875