UniProt Accession

 K1C18_HUMAN; P05783; Q53G38; Q5U0N8; Q9BW26 

Genbank Protein ID

 X12881; AY762101; BT019412; AK223093; BC000180; BC000698; BC004253; BC008636; BC020982; BC072017; AF179904; X12883; X12876 

Genbank Nucleotide ID

 CAA31375.1; AAX07828.1; AAV38219.1; BAD96813.1; AAH00180.1; AAH00698.1; AAH04253.1; AAH08636.1; AAH20982.1; AAH72017.1; AAA59461.1; CAA31377.1; CAA31369.1 

Protein Name

 Keratin, type I cytoskeletal 18 

Protein Synonyms/Alias

 Cell proliferation-inducing gene 46 protein; Cytokeratin-18; CK-18; Keratin-18; K18 

Gene Name

 KRT18 

Gene Synonyms/Alias

 CYK18; PIG46 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
81	MGGIQNEKETMQSLN	ubiquitination	[1, 2]
111	ENRRLESKIREHLEK	acetylation	[3]
131	RDWSHYFKIIEDLRA	acetylation	[3]
131	RDWSHYFKIIEDLRA	ubiquitination	[1]
167	AADDFRVKYETELAM	acetylation	[3]
167	AADDFRVKYETELAM	ubiquitination	[1, 2]
187	NDIHGLRKVIDDTNI	ubiquitination	[4]
207	ETEIEALKEELLFMK	sumoylation	[5]
214	KEELLFMKKNHEEEV	acetylation	[3]
214	KEELLFMKKNHEEEV	ubiquitination	[1]
241	TVEVDAPKSQDLAKI	ubiquitination	[2]
247	PKSQDLAKIMADIRA	ubiquitination	[1, 2, 4, 6]
317	LDSMRNLKASLENSL	ubiquitination	[2, 4, 6]
372	ALLNIKVKLEAEIAT	sumoylation	[5]
407	NSMQTIQKTTTRRIV	ubiquitination	[2, 7, 8]
417	TRRIVDGKVVSETND	ubiquitination	[2, 4, 6, 7, 8]
426	VSETNDTKVLRH***	acetylation	[3, 9]
426	VSETNDTKVLRH***	ubiquitination	[2, 4, 6, 7, 8]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Keratin hypersumoylation alters filament dynamics and is a marker for human liver disease and keratin mutation.
 Snider NT, Weerasinghe SV, Iñiguez-Lluhí JA, Herrmann H, Omary MB.
 J Biol Chem. 2011 Jan 21;286(3):2273-84. [PMID: 21062750]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [9] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773] 

Functional Description

 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. 

Sequence Annotation

 REGION 2 79 Head.
 REGION 70 373 Necessary for interaction with PNN.
 REGION 77 128 Interaction with TRADD.
 REGION 80 387 Rod.
 REGION 80 115 Coil 1A.
 REGION 116 132 Linker 1.
 REGION 133 224 Coil 1B.
 REGION 225 248 Linker 12.
 REGION 243 391 Interaction with DNAJB6.
 REGION 249 387 Coil 2.
 REGION 388 430 Tail.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 7 7 Phosphoserine.
 MOD_RES 10 10 Phosphoserine.
 MOD_RES 11 11 Phosphothreonine (By similarity).
 MOD_RES 15 15 Phosphoserine.
 MOD_RES 18 18 Phosphoserine.
 MOD_RES 30 30 Phosphoserine; alternate (By similarity).
 MOD_RES 31 31 Phosphoserine; alternate.
 MOD_RES 34 34 Phosphoserine; by CDK1.
 MOD_RES 36 36 Phosphotyrosine.
 MOD_RES 42 42 Phosphoserine.
 MOD_RES 51 51 Phosphoserine; by MAPKAPK2 and MAPKAPK3
 MOD_RES 53 53 Phosphoserine; by CAMK, PKC/PRKCE and
 MOD_RES 60 60 Phosphoserine.
 MOD_RES 65 65 Phosphothreonine.
 MOD_RES 100 100 Phosphoserine.
 MOD_RES 131 131 N6-acetyllysine.
 MOD_RES 177 177 Phosphoserine.
 MOD_RES 302 302 Phosphothreonine.
 MOD_RES 319 319 Phosphoserine.
 MOD_RES 399 399 Phosphoserine.
 MOD_RES 401 401 Phosphoserine (By similarity).
 MOD_RES 404 404 Phosphothreonine.
 MOD_RES 426 426 N6-acetyllysine.
 CARBOHYD 30 30 O-linked (GlcNAc); alternate.
 CARBOHYD 31 31 O-linked (GlcNAc); alternate.
 CARBOHYD 49 49 O-linked (GlcNAc).  

Keyword

 Acetylation; Cell cycle; Coiled coil; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Glycoprotein; Host-virus interaction; Intermediate filament; Keratin; Nucleus; Phosphoprotein; Polymorphism; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 430 AA 

Protein Sequence

Gene Ontology

 GO:0034451; C:centriolar satellite; IDA:BHF-UCL.
 GO:0045095; C:keratin filament; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005198; F:structural molecule activity; IEA:InterPro.
 GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
 GO:0006915; P:apoptotic process; IEA:Compara.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0043000; P:Golgi to plasma membrane CFTR protein transport; IDA:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Compara.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR016044; F.
 IPR001664; IF.
 IPR018039; Intermediate_filament_CS.
 IPR002957; Keratin_I. 

Pfam

 PF00038; Filament 

SMART

  

PROSITE

 PS00226; IF 

PRINTS

 PR01248; TYPE1KERATIN.