K1C18_HUMAN
ID K1C18_HUMAN Reviewed; 430 AA.
AC P05783; Q53G38; Q5U0N8; Q9BW26;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 234.
DE RecName: Full=Keratin, type I cytoskeletal 18;
DE AltName: Full=Cell proliferation-inducing gene 46 protein;
DE AltName: Full=Cytokeratin-18;
DE Short=CK-18;
DE AltName: Full=Keratin-18;
DE Short=K18;
GN Name=KRT18; Synonyms=CYK18; ORFNames=PIG46;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=2434380; DOI=10.1111/j.1432-0436.1986.tb00411.x;
RA Oshima R.G., Millan J.L., Cecena G.;
RT "Comparison of mouse and human keratin 18: a component of intermediate
RT filaments expressed prior to implantation.";
RL Differentiation 33:61-68(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a cell proliferation-inducing gene.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, Colon, Pancreas, Placenta, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-167.
RX PubMed=2454392; DOI=10.1128/mcb.8.4.1540-1550.1988;
RA Kulesh D.A., Oshima R.G.;
RT "Cloning of the human keratin 18 gene and its expression in nonepithelial
RT mouse cells.";
RL Mol. Cell. Biol. 8:1540-1550(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-430, AND TISSUE SPECIFICITY.
RC TISSUE=Vulva;
RX PubMed=2434381; DOI=10.1111/j.1432-0436.1986.tb00412.x;
RA Leube R.E., Bosch F.X., Romano V., Zimbelmann R., Hofler H., Franke W.W.;
RT "Cytokeratin expression in simple epithelia. III. Detection of mRNAs
RT encoding human cytokeratins nos. 8 and 18 in normal and tumor cells by
RT hybridization with cDNA sequences in vitro and in situ.";
RL Differentiation 33:69-85(1986).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 199-430, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=2422083; DOI=10.1111/j.1432-0436.1986.tb00787.x;
RA Romano V., Hatzfeld M., Magin T.M., Zimbelmann R., Franke W.W., Maier G.,
RA Ponstingl H.;
RT "Cytokeratin expression in simple epithelia. I. Identification of mRNA
RT coding for human cytokeratin no. 18 by a cDNA clone.";
RL Differentiation 30:244-253(1986).
RN [9]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [10]
RP GLYCOSYLATION.
RX PubMed=1371281; DOI=10.1016/s0021-9258(19)50611-1;
RA Chou C.F., Smith A.J., Omary M.B.;
RT "Characterization and dynamics of O-linked glycosylation of human
RT cytokeratin 8 and 18.";
RL J. Biol. Chem. 267:3901-3906(1992).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT SER-53, AND MUTAGENESIS OF SER-2; SER-7;
RP SER-10; SER-15; SER-18; SER-23; SER-30; SER-31; SER-34; SER-42; SER-44;
RP SER-47; SER-49; SER-51 AND SER-53.
RX PubMed=7523419; DOI=10.1083/jcb.127.1.161;
RA Ku N.O., Omary M.B.;
RT "Identification of the major physiologic phosphorylation site of human
RT keratin 18: potential kinases and a role in filament reorganization.";
RL J. Cell Biol. 127:161-171(1994).
RN [12]
RP GLYCOSYLATION AT SER-30; SER-31 AND SER-49, MUTAGENESIS OF SER-30; SER-31
RP AND SER-49, CLEAVAGE OF INITIATOR METHIONINE, AND ACETYLATION AT SER-2.
RX PubMed=7538124; DOI=10.1074/jbc.270.20.11820;
RA Ku N.-O., Omary M.B.;
RT "Identification and mutational analysis of the glycosylation sites of human
RT keratin 18.";
RL J. Biol. Chem. 270:11820-11827(1995).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ARG-90.
RX PubMed=8522591; DOI=10.1083/jcb.131.5.1303;
RA Ku N.O., Michie S., Oshima R.G., Omary M.B.;
RT "Chronic hepatitis, hepatocyte fragility, and increased soluble
RT phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved
RT arginine mutant.";
RL J. Cell Biol. 131:1303-1314(1995).
RN [14]
RP PHOSPHORYLATION, AND INTERACTION WITH YWHAE; YWHAH AND YWHAZ.
RX PubMed=8609167; DOI=10.1083/jcb.133.2.345;
RA Liao J., Omary M.B.;
RT "14-3-3 proteins associate with phosphorylated simple epithelial keratins
RT during cell cycle progression and act as a solubility cofactor.";
RL J. Cell Biol. 133:345-357(1996).
RN [15]
RP FUNCTION, CLEAVAGE BY CASPASES, AND MUTAGENESIS OF SER-53 AND ASP-238.
RX PubMed=9298992; DOI=10.1083/jcb.138.6.1379;
RA Caulin C., Salvesen G.S., Oshima R.G.;
RT "Caspase cleavage of keratin 18 and reorganization of intermediate
RT filaments during epithelial cell apoptosis.";
RL J. Cell Biol. 138:1379-1394(1997).
RN [16]
RP FUNCTION, INTERACTION WITH YWHAE AND YWHAZ, PHOSPHORYLATION AT SER-34, AND
RP MUTAGENESIS OF SER-34 AND SER-53.
RX PubMed=9524113; DOI=10.1093/emboj/17.7.1892;
RA Ku N.O., Liao J., Omary M.B.;
RT "Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3
RT proteins.";
RL EMBO J. 17:1892-1906(1998).
RN [17]
RP INTERACTION WITH PNN.
RX PubMed=10809736; DOI=10.1074/jbc.275.20.14910;
RA Shi J., Sugrue S.P.;
RT "Dissection of protein linkage between keratins and pinin, a protein with
RT dual location at desmosome-intermediate filament complex and in the
RT nucleus.";
RL J. Biol. Chem. 275:14910-14915(2000).
RN [18]
RP INTERACTION WITH DNAJB6.
RX PubMed=10954706; DOI=10.1074/jbc.m003492200;
RA Izawa I., Nishizawa M., Ohtakara K., Ohtsuka K., Inada H., Inagaki M.;
RT "Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18
RT filament regulatory protein.";
RL J. Biol. Chem. 275:34521-34527(2000).
RN [19]
RP INTERACTION WITH TRADD.
RX PubMed=11684708; DOI=10.1083/jcb.200103078;
RA Inada H., Izawa I., Nishizawa M., Fujita E., Kiyono T., Takahashi T.,
RA Momoi T., Inagaki M.;
RT "Keratin attenuates tumor necrosis factor-induced cytotoxicity through
RT association with TRADD.";
RL J. Cell Biol. 155:415-426(2001).
RN [20]
RP ASSOCIATION WITH KRT8.
RX PubMed=14756564; DOI=10.1021/bi035072s;
RA Waseem A., Karsten U., Leigh I.M., Purkis P., Waseem N.H., Lane E.B.;
RT "Conformational changes in the rod domain of human keratin 8 following
RT heterotypic association with keratin 18 and its implication for filament
RT stability.";
RL Biochemistry 43:1283-1295(2004).
RN [21]
RP PHOSPHORYLATION AT SER-34 AND SER-53.
RX PubMed=15368451; DOI=10.1002/hep.20277;
RA Toivola D.M., Ku N.O., Resurreccion E.Z., Nelson D.R., Wright T.L.,
RA Omary M.B.;
RT "Keratin 8 and 18 hyperphosphorylation is a marker of progression of human
RT liver disease.";
RL Hepatology 40:459-466(2004).
RN [22]
RP FUNCTION, INTERACTION WITH MUTATED CFTR, AND SUBCELLULAR LOCATION.
RX PubMed=15529338; DOI=10.1002/pmic.200400850;
RA Davezac N., Tondelier D., Lipecka J., Fanen P., Demaugre F., Debski J.,
RA Dadlez M., Schrattenholz A., Cahill M.A., Edelman A.;
RT "Global proteomic approach unmasks involvement of keratins 8 and 18 in the
RT delivery of cystic fibrosis transmembrane conductance regulator
RT (CFTR)/deltaF508-CFTR to the plasma membrane.";
RL Proteomics 4:3833-3844(2004).
RN [23]
RP INTERACTION WITH TCHP.
RX PubMed=15731013; DOI=10.1242/jcs.01667;
RA Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T.,
RA Usukura J., Inagaki M.;
RT "Identification of trichoplein, a novel keratin filament-binding protein.";
RL J. Cell Sci. 118:1081-1090(2005).
RN [24]
RP INTERACTION WITH HEPATITIS C VIRUS CORE PROTEIN (MICROBIAL INFECTION).
RX PubMed=15846844; DOI=10.1002/pmic.200401093;
RA Kang S.-M., Shin M.-J., Kim J.-H., Oh J.-W.;
RT "Proteomic profiling of cellular proteins interacting with the hepatitis C
RT virus core protein.";
RL Proteomics 5:2227-2237(2005).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-53.
RX PubMed=16424149; DOI=10.1124/jpet.105.097667;
RA Lipecka J., Norez C., Bensalem N., Baudouin-Legros M., Planelles G.,
RA Becq F., Edelman A., Davezac N.;
RT "Rescue of DeltaF508-CFTR (cystic fibrosis transmembrane conductance
RT regulator) by curcumin: involvement of the keratin 18 network.";
RL J. Pharmacol. Exp. Ther. 317:500-505(2006).
RN [27]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND INDUCTION.
RX PubMed=17213200; DOI=10.1074/jbc.m604068200;
RA Wang L., Srinivasan S., Theiss A.L., Merlin D., Sitaraman S.V.;
RT "Interleukin-6 induces keratin expression in intestinal epithelial cells:
RT potential role of keratin-8 in interleukin-6-induced barrier function
RT alterations.";
RL J. Biol. Chem. 282:8219-8227(2007).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-34; SER-42; SER-60;
RP THR-302 AND SER-399, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-131 AND LYS-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [32]
RP GLYCOSYLATION AT SER-30; SER-31 AND SER-49.
RX PubMed=20729549; DOI=10.1074/jbc.m109.098996;
RA Srikanth B., Vaidya M.M., Kalraiya R.D.;
RT "O-GlcNAcylation determines the solubility, filament organization, and
RT stability of keratins 8 and 18.";
RL J. Biol. Chem. 285:34062-34071(2010).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-15; SER-34; SER-42;
RP SER-60; THR-65; SER-100; SER-319; SER-399 AND THR-404, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [36]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=22002106; DOI=10.1074/mcp.m111.013680;
RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.;
RT "Systematic analysis of protein pools, isoforms, and modifications
RT affecting turnover and subcellular localization.";
RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [38]
RP INTERACTION WITH FAM83H.
RX PubMed=23902688; DOI=10.1242/jcs.129684;
RA Kuga T., Kume H., Kawasaki N., Sato M., Adachi J., Shiromizu T.,
RA Hoshino I., Nishimori T., Matsubara H., Tomonaga T.;
RT "A novel mechanism of keratin cytoskeleton organization through casein
RT kinase Ialpha and FAM83H in colorectal cancer.";
RL J. Cell Sci. 126:4721-4731(2013).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-18; SER-34; SER-49;
RP THR-52; SER-60; SER-93; SER-305; SER-319; SER-323 AND SER-399, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [40]
RP IDENTIFICATION IN A COMPLEX WITH KRT8, AND INTERACTION WITH KRT8 AND PLEC.
RX PubMed=24940650; DOI=10.1038/jid.2014.255;
RA Bouameur J.E., Favre B., Fontao L., Lingasamy P., Begre N., Borradori L.;
RT "Interaction of plectin with keratins 5 and 14: dependence on several
RT plectin domains and keratin quaternary structure.";
RL J. Invest. Dermatol. 134:2776-2783(2014).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-65; SER-177; SER-305;
RP SER-398; SER-399; SER-401 AND THR-404, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [42]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-45 AND ARG-55, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [43]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-426, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [44]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-81; LYS-247; LYS-370; LYS-372;
RP LYS-417 AND LYS-426, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [45]
RP VARIANT CIRRH LEU-128.
RX PubMed=9011570; DOI=10.1172/jci119127;
RA Ku N.-O., Wright T.L., Terrault N.A., Gish R., Omary M.B.;
RT "Mutation of human keratin 18 in association with cryptogenic cirrhosis.";
RL J. Clin. Invest. 99:19-23(1997).
RN [46]
RP VARIANTS CIRRH ALA-103; LEU-128; GLN-261 AND ARG-340, AND VARIANT THR-230.
RX PubMed=12724528; DOI=10.1073/pnas.0936165100;
RA Ku N.-O., Darling J.M., Krams S.M., Esquivel C.O., Keeffe E.B.,
RA Sibley R.K., Lee Y.M., Wright T.L., Omary M.B.;
RT "Keratin 8 and 18 mutations are risk factors for developing liver disease
RT of multiple etiologies.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6063-6068(2003).
CC -!- FUNCTION: Involved in the uptake of thrombin-antithrombin complexes by
CC hepatic cells (By similarity). When phosphorylated, plays a role in
CC filament reorganization. Involved in the delivery of mutated CFTR to
CC the plasma membrane. Together with KRT8, is involved in interleukin-6
CC (IL-6)-mediated barrier protection. {ECO:0000250,
CC ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149,
CC ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419,
CC ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992,
CC ECO:0000269|PubMed:9524113}.
CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins. KRT18
CC associates with KRT8 (PubMed:24940650). Interacts with PLEC isoform 1C,
CC when in a heterodimer with KRT8 (PubMed:24940650). Interacts with the
CC thrombin-antithrombin complex (By similarity). Interacts with PNN and
CC mutated CFTR. Interacts with YWHAE, YWHAH and YWHAZ only when
CC phosphorylated. Interacts with DNAJB6, TCHP and TRADD. Interacts with
CC FAM83H (PubMed:23902688). Interacts with EPPK1 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P05784,
CC ECO:0000269|PubMed:10809736, ECO:0000269|PubMed:10954706,
CC ECO:0000269|PubMed:11684708, ECO:0000269|PubMed:15529338,
CC ECO:0000269|PubMed:15731013, ECO:0000269|PubMed:23902688,
CC ECO:0000269|PubMed:24940650, ECO:0000269|PubMed:8609167,
CC ECO:0000269|PubMed:9524113}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus/HCV
CC core protein. {ECO:0000269|PubMed:15846844}.
CC -!- INTERACTION:
CC P05783; Q14457: BECN1; NbExp=2; IntAct=EBI-297888, EBI-949378;
CC P05783; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-297888, EBI-8643161;
CC P05783; Q8IYE0-2: CCDC146; NbExp=3; IntAct=EBI-297888, EBI-10247802;
CC P05783; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-297888, EBI-10175300;
CC P05783; O75190: DNAJB6; NbExp=6; IntAct=EBI-297888, EBI-1053164;
CC P05783; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-297888, EBI-743105;
CC P05783; Q08379: GOLGA2; NbExp=7; IntAct=EBI-297888, EBI-618309;
CC P05783; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-297888, EBI-2514791;
CC P05783; A0A0S2Z4Q4: HGS; NbExp=3; IntAct=EBI-297888, EBI-16429135;
CC P05783; O14964: HGS; NbExp=7; IntAct=EBI-297888, EBI-740220;
CC P05783; P42858: HTT; NbExp=6; IntAct=EBI-297888, EBI-466029;
CC P05783; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-297888, EBI-81279;
CC P05783; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-297888, EBI-14069005;
CC P05783; P02538: KRT6A; NbExp=3; IntAct=EBI-297888, EBI-702198;
CC P05783; P48668: KRT6C; NbExp=4; IntAct=EBI-297888, EBI-2564105;
CC P05783; Q3SY84: KRT71; NbExp=3; IntAct=EBI-297888, EBI-2952676;
CC P05783; Q5XKE5: KRT79; NbExp=3; IntAct=EBI-297888, EBI-2514135;
CC P05783; P05787: KRT8; NbExp=16; IntAct=EBI-297888, EBI-297852;
CC P05783; Q14533: KRT81; NbExp=3; IntAct=EBI-297888, EBI-739648;
CC P05783; O75022: LILRB3; NbExp=3; IntAct=EBI-297888, EBI-2830524;
CC P05783; Q9BQ69: MACROD1; NbExp=7; IntAct=EBI-297888, EBI-5324932;
CC P05783; P07196: NEFL; NbExp=3; IntAct=EBI-297888, EBI-475646;
CC P05783; Q9Y5B8: NME7; NbExp=4; IntAct=EBI-297888, EBI-744782;
CC P05783; Q13835-2: PKP1; NbExp=4; IntAct=EBI-297888, EBI-9087684;
CC P05783; A0A0S2Z505: PSTPIP2; NbExp=3; IntAct=EBI-297888, EBI-16437709;
CC P05783; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-297888, EBI-1504830;
CC P05783; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-297888, EBI-6872807;
CC P05783; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-297888, EBI-750487;
CC P05783; Q15628: TRADD; NbExp=11; IntAct=EBI-297888, EBI-359215;
CC P05783; Q99816: TSG101; NbExp=4; IntAct=EBI-297888, EBI-346882;
CC P05783; B7UM99: tir; Xeno; NbExp=5; IntAct=EBI-297888, EBI-2504426;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:Q5BJY9}.
CC Cytoplasm, perinuclear region. Nucleus, nucleolus
CC {ECO:0000269|PubMed:22002106}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q5BJY9}.
CC -!- TISSUE SPECIFICITY: Expressed in colon, placenta, liver and very weakly
CC in exocervix. Increased expression observed in lymph nodes of breast
CC carcinoma. {ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:2422083,
CC ECO:0000269|PubMed:2434380, ECO:0000269|PubMed:2434381}.
CC -!- INDUCTION: By IL6/interleukin-6. {ECO:0000269|PubMed:17213200}.
CC -!- PTM: Phosphorylation at Ser-34 increases during mitosis.
CC Hyperphosphorylated at Ser-53 in diseased cirrhosis liver.
CC Phosphorylation increases by IL-6. {ECO:0000269|PubMed:15368451,
CC ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200,
CC ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8609167,
CC ECO:0000269|PubMed:9524113}.
CC -!- PTM: Proteolytically cleaved by caspases during epithelial cell
CC apoptosis. Cleavage occurs at Asp-238 by either caspase-3, caspase-6 or
CC caspase-7. {ECO:0000269|PubMed:9298992}.
CC -!- PTM: O-GlcNAcylation increases solubility, and decreases stability by
CC inducing proteasomal degradation.
CC -!- DISEASE: Cirrhosis (CIRRH) [MIM:215600]: A liver disease characterized
CC by severe panlobular liver-cell swelling with Mallory body formation,
CC prominent pericellular fibrosis, and marked deposits of copper.
CC Clinical features include abdomen swelling, jaundice and pulmonary
CC hypertension. {ECO:0000269|PubMed:12724528,
CC ECO:0000269|PubMed:9011570}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and microfibrillar
CC keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
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DR EMBL; X12881; CAA31375.1; -; mRNA.
DR EMBL; AY762101; AAX07828.1; -; mRNA.
DR EMBL; BT019412; AAV38219.1; -; mRNA.
DR EMBL; AK223093; BAD96813.1; -; mRNA.
DR EMBL; BC000180; AAH00180.1; -; mRNA.
DR EMBL; BC000698; AAH00698.1; -; mRNA.
DR EMBL; BC004253; AAH04253.1; -; mRNA.
DR EMBL; BC008636; AAH08636.1; -; mRNA.
DR EMBL; BC020982; AAH20982.1; -; mRNA.
DR EMBL; BC072017; AAH72017.1; -; mRNA.
DR EMBL; AF179904; AAA59461.1; -; Genomic_DNA.
DR EMBL; X12883; CAA31377.1; -; mRNA.
DR EMBL; X12876; CAA31369.1; -; mRNA.
DR CCDS; CCDS31809.1; -.
DR PIR; S05481; S05481.
DR RefSeq; NP_000215.1; NM_000224.2.
DR RefSeq; NP_954657.1; NM_199187.1.
DR AlphaFoldDB; P05783; -.
DR SMR; P05783; -.
DR BioGRID; 110073; 290.
DR ComplexPortal; CPX-5661; Keratin-8 - Keratin-18 dimer complex.
DR DIP; DIP-633N; -.
DR IntAct; P05783; 114.
DR MINT; P05783; -.
DR STRING; 9606.ENSP00000373487; -.
DR GlyConnect; 312; 3 N-Linked glycans (1 site), 1 O-Linked glycan (2 sites).
DR GlyGen; P05783; 7 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (6 sites).
DR iPTMnet; P05783; -.
DR MetOSite; P05783; -.
DR PhosphoSitePlus; P05783; -.
DR SwissPalm; P05783; -.
DR BioMuta; KRT18; -.
DR DMDM; 125083; -.
DR SWISS-2DPAGE; P05783; -.
DR CPTAC; CPTAC-1518; -.
DR CPTAC; CPTAC-1519; -.
DR EPD; P05783; -.
DR jPOST; P05783; -.
DR MassIVE; P05783; -.
DR MaxQB; P05783; -.
DR PaxDb; P05783; -.
DR PeptideAtlas; P05783; -.
DR PRIDE; P05783; -.
DR ProteomicsDB; 51857; -.
DR TopDownProteomics; P05783; -.
DR ABCD; P05783; 4 sequenced antibodies.
DR Antibodypedia; 271; 3642 antibodies from 57 providers.
DR DNASU; 3875; -.
DR Ensembl; ENST00000388835.4; ENSP00000373487.3; ENSG00000111057.11.
DR Ensembl; ENST00000388837.6; ENSP00000373489.2; ENSG00000111057.11.
DR GeneID; 3875; -.
DR KEGG; hsa:3875; -.
DR MANE-Select; ENST00000388835.4; ENSP00000373487.3; NM_000224.3; NP_000215.1.
DR UCSC; uc001sbe.4; human.
DR CTD; 3875; -.
DR DisGeNET; 3875; -.
DR GeneCards; KRT18; -.
DR HGNC; HGNC:6430; KRT18.
DR HPA; ENSG00000111057; Low tissue specificity.
DR MalaCards; KRT18; -.
DR MIM; 148070; gene.
DR MIM; 215600; phenotype.
DR neXtProt; NX_P05783; -.
DR OpenTargets; ENSG00000111057; -.
DR PharmGKB; PA30217; -.
DR VEuPathDB; HostDB:ENSG00000111057; -.
DR eggNOG; ENOG502QUS8; Eukaryota.
DR GeneTree; ENSGT00940000153309; -.
DR InParanoid; P05783; -.
DR OMA; YRASSIH; -.
DR OrthoDB; 711591at2759; -.
DR PhylomeDB; P05783; -.
DR TreeFam; TF332742; -.
DR PathwayCommons; P05783; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P05783; -.
DR SIGNOR; P05783; -.
DR BioGRID-ORCS; 3875; 90 hits in 1079 CRISPR screens.
DR ChiTaRS; KRT18; human.
DR GeneWiki; Keratin_18; -.
DR GenomeRNAi; 3875; -.
DR Pharos; P05783; Tbio.
DR PRO; PR:P05783; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P05783; protein.
DR Bgee; ENSG00000111057; Expressed in endometrium epithelium and 171 other tissues.
DR ExpressionAtlas; P05783; baseline and differential.
DR Genevisible; P05783; HS.
DR GO; GO:0005912; C:adherens junction; HDA:BHF-UCL.
DR GO; GO:0071944; C:cell periphery; IEA:Ensembl.
DR GO; GO:0034451; C:centriolar satellite; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; IDA:BHF-UCL.
DR GO; GO:0045095; C:keratin filament; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; HDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0043000; P:Golgi to plasma membrane CFTR protein transport; IDA:UniProtKB.
DR GO; GO:0097284; P:hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR027695; Keratin-18.
DR InterPro; IPR002957; Keratin_I.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR PANTHER; PTHR23239:SF349; PTHR23239:SF349; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01248; TYPE1KERATIN.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Coiled coil; Cytoplasm; Direct protein sequencing;
KW Disease variant; Glycoprotein; Host-virus interaction;
KW Intermediate filament; Isopeptide bond; Keratin; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7538124"
FT CHAIN 2..430
FT /note="Keratin, type I cytoskeletal 18"
FT /id="PRO_0000063666"
FT DOMAIN 80..391
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 2..79
FT /note="Head"
FT REGION 70..373
FT /note="Necessary for interaction with PNN"
FT /evidence="ECO:0000269|PubMed:10809736"
FT REGION 77..128
FT /note="Interaction with TRADD"
FT /evidence="ECO:0000269|PubMed:11684708"
FT REGION 80..115
FT /note="Coil 1A"
FT REGION 116..132
FT /note="Linker 1"
FT REGION 133..224
FT /note="Coil 1B"
FT REGION 225..248
FT /note="Linker 12"
FT REGION 243..391
FT /note="Interaction with DNAJB6"
FT /evidence="ECO:0000269|PubMed:10954706"
FT REGION 249..387
FT /note="Coil 2"
FT REGION 388..430
FT /note="Tail"
FT SITE 238..239
FT /note="Cleavage; by caspase-3, caspase-6 or caspase-7"
FT SITE 271
FT /note="Stutter"
FT SITE 331
FT /note="Stutter"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:7538124"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17924679,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 30
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05784"
FT MOD_RES 31
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05784"
FT MOD_RES 34
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:15368451,
FT ECO:0000269|PubMed:9524113, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 36
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P05784"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 45
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 49
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 51
FT /note="Phosphoserine; by MAPKAPK2 and MAPKAPK3"
FT /evidence="ECO:0000250|UniProtKB:P05784"
FT MOD_RES 52
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 53
FT /note="Phosphoserine; by CAMK, PKC/PRKCE and AURKA"
FT /evidence="ECO:0000269|PubMed:15368451,
FT ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:7523419"
FT MOD_RES 55
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 65
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 131
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 302
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 404
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 426
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CARBOHYD 30
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:20729549,
FT ECO:0000269|PubMed:7538124"
FT /id="CAR_000175"
FT CARBOHYD 31
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:20729549,
FT ECO:0000269|PubMed:7538124"
FT /id="CAR_000193"
FT CARBOHYD 49
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:20729549,
FT ECO:0000269|PubMed:7538124"
FT /id="CAR_000194"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 247
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 370
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 372
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 417
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 426
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 426
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 103
FT /note="T -> A (in CIRRH; dbSNP:rs61136606)"
FT /evidence="ECO:0000269|PubMed:12724528"
FT /id="VAR_023054"
FT VARIANT 128
FT /note="H -> L (in CIRRH; interfers with the ability to form
FT normal filaments; dbSNP:rs57758506)"
FT /evidence="ECO:0000269|PubMed:12724528,
FT ECO:0000269|PubMed:9011570"
FT /id="VAR_003852"
FT VARIANT 230
FT /note="S -> T (in dbSNP:rs58472472)"
FT /evidence="ECO:0000269|PubMed:12724528"
FT /id="VAR_023055"
FT VARIANT 261
FT /note="R -> Q (in CIRRH; dbSNP:rs57354642)"
FT /evidence="ECO:0000269|PubMed:12724528"
FT /id="VAR_023056"
FT VARIANT 340
FT /note="G -> R (in CIRRH; dbSNP:rs57370769)"
FT /evidence="ECO:0000269|PubMed:12724528"
FT /id="VAR_023057"
FT MUTAGEN 2
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-7 and A-10."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 7
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-2 and A-10."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 10
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-2 and A-7."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 15
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-18 and A-23. Abolishes phosphorylation; when
FT associated with A-18; A-34; A-47; A-49; A-51 and A-53."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 18
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-15 and A-23. Abolishes phosphorylation; when
FT associated with A-15; A-34; A-47; A-49; A-51 and A-53."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 23
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-15 and A-18."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 30
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-31 and A-34, or with A-31; A-44 and A-51. Abolishes
FT glycosylation but does not affect binding to YWHAE and
FT YWHAZ; when associated with A-31 and A-49."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:7538124"
FT MUTAGEN 31
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-30 and A-34, or with A-30; A-44 and A-51. Abolishes
FT glycosylation but does not affect binding to YWHAE and
FT YWHAZ; when associated with A-30 and A-49."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:7538124"
FT MUTAGEN 34
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-30 and A-31. Abolishes phosphorylation; when
FT associated with A-15; A-18; A-47; A-49; A-51 and A-53.
FT Abolishes binding to YWHAE and YWHAZ; and when associated
FT with A-53."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:9524113"
FT MUTAGEN 34
FT /note="S->D,E: Abolishes binding to YWHAE and YWHAZ."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:9524113"
FT MUTAGEN 42
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-44."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 44
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-42, or with A-30; A-31 and A-51."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 47
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-49. Abolishes phosphorylation; when associated with
FT A-49; A-51 and A-53, or with A-15; A-18; A-34; A-49; A-51
FT and A-53."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 49
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-47. Abolishes phosphorylation; when associated with
FT A-47; A-51 and A-53, or with A-15; A-18; A-34; A-47; A-51
FT and A-53. Abolishes glycosylation but does not affect
FT binding to YWHAE and YWHAZ; when associated with A-30 and
FT A-31."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:7538124"
FT MUTAGEN 51
FT /note="S->A: No effect on phosphorylation; when associated
FT with A-30; A-31 and A-47. Abolishes phosphorylation; when
FT associated with A-47; A-49 and A-53, or with A-15; A-18; A-
FT 34; A-47; A-49 and A-53."
FT /evidence="ECO:0000269|PubMed:7523419"
FT MUTAGEN 53
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-47; A-49 and A-51, or with A-15; A-18; A-34; A-47;
FT A-49 and A-51. Abolishes binding to YWHAE and YWHAZ; when
FT associated with A-34. No effect on caspase cleavage during
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:7523419,
FT ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113"
FT MUTAGEN 90
FT /note="R->C,H: In transgenic mice, induces marked
FT disruption of liver and pancreas keratin filament network.
FT Increases phosphorylation and glycosylation."
FT /evidence="ECO:0000269|PubMed:8522591"
FT MUTAGEN 238
FT /note="D->E: Prevents cleavage by caspase-6 during
FT apoptosis. Induces aggregates of keratin filaments in an
FT altered organization."
FT /evidence="ECO:0000269|PubMed:9298992"
FT CONFLICT 168
FT /note="Y -> H (in Ref. 5; AAH00698)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="E -> Q (in Ref. 8; CAA31369)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="E -> G (in Ref. 3; BAD96813)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="A -> S (in Ref. 8; CAA31369)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="D -> R (in Ref. 8; CAA31369)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="S -> R (in Ref. 8; CAA31369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 48058 MW; 1E5604C6BCC7A17A CRC64;
MSFTTRSTFS TNYRSLGSVQ APSYGARPVS SAASVYAGAG GSGSRISVSR STSFRGGMGS
GGLATGIAGG LAGMGGIQNE KETMQSLNDR LASYLDRVRS LETENRRLES KIREHLEKKG
PQVRDWSHYF KIIEDLRAQI FANTVDNARI VLQIDNARLA ADDFRVKYET ELAMRQSVEN
DIHGLRKVID DTNITRLQLE TEIEALKEEL LFMKKNHEEE VKGLQAQIAS SGLTVEVDAP
KSQDLAKIMA DIRAQYDELA RKNREELDKY WSQQIEESTT VVTTQSAEVG AAETTLTELR
RTVQSLEIDL DSMRNLKASL ENSLREVEAR YALQMEQLNG ILLHLESELA QTRAEGQRQA
QEYEALLNIK VKLEAEIATY RRLLEDGEDF NLGDALDSSN SMQTIQKTTT RRIVDGKVVS
ETNDTKVLRH
