Details of Host Protein

 Host Protein General Information (ID: PT0587)
  Protein Name
Keratin, type I cytoskeletal 18 (KRT18)
  Gene Name
KRT18
  Host Species
Homo sapiens
  Uniprot Entry Name
K1C18_HUMAN
  Protein Families
Intermediate filament family
  Subcellular Location
Cytoplasm; perinuclear region
  External Link
NCBI Gene ID
3875
Uniprot ID
P05783
Ensembl ID
ENSG00000111057
HGNC ID
HGNC:6430
  Function in Host
Involved in the uptake of thrombin-antithrombin complexes byhepatic cells. When phosphorylated, plays a role infilament reorganization. Involved in the delivery of mutated CFTR tothe plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6) -mediated barrier protection. [1-7]
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  Related KEGG Pathway
Staphylococcus aureus infection hsa05150            Pathway Map 
Estrogen signaling pathway hsa04915            Pathway Map 
  3D Structure
AlphaFold ID: P05783 
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  mmCIF File Download   
  PDB File Download   

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [8]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein KRT18 in viral infection, KRT18 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of KRT18 leads to the decreased SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: Not Specified Virus Region (hCoV-19/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-19/England/02/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Calu-3 cells (Human lung cancer cell)  (CVCL_0609 )
              Cell Originated Tissue Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.042
              Method Description UV protein-RNA crosslinking; RNA interactome capture (cRIC); RNA antisense purification coupled with mass spectrometry (RAP-MS)

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
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Protein Phosphorylation after Virus Infection
S100 [10]
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S127 [10]
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S15 [10]
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S177 [10]
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S18 [10]
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S23 [10]
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S30 [10]
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S31 [10]
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S323 [10]
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S34 [10]
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S401 [10]
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S42 [10]
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S420 [10]
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S49 [11]
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S60 [10]
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S7 [10]
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S93 [10]
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T195 [10]
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T65 [10]
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Y24 [10]
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Y36 [10]
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Protein Sequence Information
MSFTTRSTFSTNYRSLGSVQAPSYGARPVSSAASVYAGAGGSGSRISVSRSTSFRGGMGSGGLATGIAGGLAGMGGIQNEKETMQSLNDRLASYLDRVRSLETENRRLESKIREHLEKKGPQVRDWSHYFKIIEDLRAQIFANTVDNARIVLQIDNARLAADDFRVKYETELAMRQSVENDIHGLRKVIDDTNITRLQLETEIEALKEELLFMKKNHEEEVKGLQAQIASSGLTVEVDAPKSQDLAKIMADIRAQYDELARKNREELDKYWSQQIEESTTVVTTQSAEVGAAETTLTELRRTVQSLEIDLDSMRNLKASLENSLREVEARYALQMEQLNGILLHLESELAQTRAEGQRQAQEYEALLNIKVKLEAEIATYRRLLEDGEDFNLGDALDSSNSMQTIQKTTTRRIVDGKVVSETNDTKVLRH
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References
1 Interleukin-6 induces keratin expression in intestinal epithelial cells: potential role of keratin-8 in interleukin-6-induced barrier function alterations. J Biol Chem. 2007 Mar 16;282(11):8219-27.
2 Rescue of DeltaF508-CFTR (cystic fibrosis transmembrane conductance regulator) by curcumin: involvement of the keratin 18 network. J Pharmacol Exp Ther. 2006 May;317(2):500-5.
3 Global proteomic approach unmasks involvement of keratins 8 and 18 in the delivery of cystic fibrosis transmembrane conductance regulator (CFTR)/deltaF508-CFTR to the plasma membrane. Proteomics. 2004 Dec;4(12):3833-44.
4 Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3 proteins. EMBO J. 1998 Apr 1;17(7):1892-906.
5 Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. J Cell Biol. 1997 Sep 22;138(6):1379-94.
6 Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant. J Cell Biol. 1995 Dec;131(5):1303-14.
7 Identification of the major physiologic phosphorylation site of human keratin 18: potential kinases and a role in filament reorganization. J Cell Biol. 1994 Oct;127(1):161-71.
8 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
9 Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021 Jul 1;81(13):2851-2867.e7.
10 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
11 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.