Details of Host Protein

 Host Protein General Information (ID: PT1253)
  Protein Name
Werner syndrome ATP-dependent helicase (WRN)
  Gene Name
WRN
  Host Species
Homo sapiens
  Uniprot Entry Name
WRN_HUMAN
  Protein Families
Helicase family
  EC Number
3.6.4.12; 3.1.-.-
  Subcellular Location
Nucleus; nucleolus Nucleus
  External Link
NCBI Gene ID
7486
Uniprot ID
Q14191
Ensembl ID
ENSG00000165392
HGNC ID
HGNC:12791
  Function in Host
Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towardsdouble-stranded DNA with a 5'-overhang. Has no nuclease activitytowards single-stranded DNA or blunt-ended double-stranded DNA. Bindspreferentially to DNA substrates containing alternate secondarystructures, such as replication forks and Holliday junctions. May playan important role in the dissociation of joint DNA molecules that canarise as products of homologous recombination, at stalled replicationforks or during DNA repair. Alleviates stalling of DNA polymerases atthe site of DNA lesions. Important for genomic integrity. Plays a rolein the formation of DNA replication focal centers; stably associateswith foci elements generating binding sites for RP-A. Plays a role in double-strand break repair after gamma-irradiation. [1-7]
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  3D Structure
PDB ID: 2AXL 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-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 WRN in viral infection, WRN protein Knockdown 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 WRN increases SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network
  Network Download  

 Full List of Virus RNA Interacting with This Protien
            RNA Region: N region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
N region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCoV-SARS/Manitoba/2003 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-SARS/Manitoba/2003
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome-related coronavirus (HCoV-SARS)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-OC43/VR-759 Quebec/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCov-OC43/VR-759 Quebec/2019
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus OC43 (HCov-OC43)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-NL63/Amsterdam/2004 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCov-NL63/Amsterdam/2004
              Strains Family
Alpha
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human Coronavirus NL63 (HCov-NL63)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-MERS/Jeddah/2012 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCov-MERS/Jeddah/2012
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Middle East respiratory syndrome-related coronavirus (HCov-MERS)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCoV-HKU1/Hong Kong/2004 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-HKU1/Hong Kong/2004
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus HKU1 (HCoV-HKU1)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-229E/Würzburg/2000 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCov-229E/Würzburg/2000
              Strains Family
Alpha
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus 229E (HCov-229E)
              Interaction Type Potential binding protein
              Infection Cells K562 cells (Human leukemic cell line) K562 cells (Human leukemic cell line)  (CVCL_0004 )
              Cell Originated Tissue Bone marrow
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm

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
  PNG Download  
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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
  PNG Download  
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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
  PNG Download  
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Protein Phosphorylation after Virus Infection
S1133 [10]
  PNG Download  
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Protein Sequence Information
MSEKKLETTAQQRKCPEWMNVQNKRCAVEERKACVRKSVFEDDLPFLEFTGSIVYSYDASDCSFLSEDISMSLSDGDVVGFDMEWPPLYNRGKLGKVALIQLCVSESKCYLFHVSSMSVFPQGLKMLLENKAVKKAGVGIEGDQWKLLRDFDIKLKNFVELTDVANKKLKCTETWSLNSLVKHLLGKQLLKDKSIRCSNWSKFPLTEDQKLYAATDAYAGFIIYRNLEILDDTVQRFAINKEEEILLSDMNKQLTSISEEVMDLAKHLPHAFSKLENPRRVSILLKDISENLYSLRRMIIGSTNIETELRPSNNLNLLSFEDSTTGGVQQKQIREHEVLIHVEDETWDPTLDHLAKHDGEDVLGNKVERKEDGFEDGVEDNKLKENMERACLMSLDITEHELQILEQQSQEEYLSDIAYKSTEHLSPNDNENDTSYVIESDEDLEMEMLKHLSPNDNENDTSYVIESDEDLEMEMLKSLENLNSGTVEPTHSKCLKMERNLGLPTKEEEEDDENEANEGEEDDDKDFLWPAPNEEQVTCLKMYFGHSSFKPVQWKVIHSVLEERRDNVAVMATGYGKSLCFQYPPVYVGKIGLVISPLISLMEDQVLQLKMSNIPACFLGSAQSENVLTDIKLGKYRIVYVTPEYCSGNMGLLQQLEADIGITLIAVDEAHCISEWGHDFRDSFRKLGSLKTALPMVPIVALTATASSSIREDIVRCLNLRNPQITCTGFDRPNLYLEVRRKTGNILQDLQPFLVKTSSHWEFEGPTIIYCPSRKMTQQVTGELRKLNLSCGTYHAGMSFSTRKDIHHRFVRDEIQCVIATIAFGMGINKADIRQVIHYGAPKDMESYYQEIGRAGRDGLQSSCHVLWAPADINLNRHLLTEIRNEKFRLYKLKMMAKMEKYLHSSRCRRQIILSHFEDKQVQKASLGIMGTEKCCDNCRSRLDHCYSMDDSEDTSWDFGPQAFKLLSAVDILGEKFGIGLPILFLRGSNSQRLADQYRRHSLFGTGKDQTESWWKAFSRQLITEGFLVEVSRYNKFMKICALTKKGRNWLHKANTESQSLILQANEELCPKKLLLPSSKTVSSGTKEHCYNQVPVELSTEKKSNLEKLYSYKPCDKISSGSNISKKSIMVQSPEKAYSSSQPVISAQEQETQIVLYGKLVEARQKHANKMDVPPAILATNKILVDMAKMRPTTVENVKRIDGVSEGKAAMLAPLLEVIKHFCQTNSVQTDLFSSTKPQEEQKTSLVAKNKICTLSQSMAITYSLFQEKKMPLKSIAESRILPLMTIGMHLSQAVKAGCPLDLERAGLTPEVQKIIADVIRNPPVNSDMSKISLIRMLVPENIDTYLIHMAIEILKHGPDSGLQPSCDVNKRRCFPGSEEICSSSKRSKEEVGINTETSSAERKRRLPVWFAKGSDTSKKLMDKTKRGGLFS
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References
1 Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in irradiation-induced DNA damage responses. Biochemistry (Mosc). 2011 May;76(5):550-4.
2 A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3 - 5 exonuclease and 5 -protruding strand endonuclease activities. Biochemistry. 2002 Mar 5;41(9):2901-12.
3 The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins. Nat Commun. 2016 Apr 11;7:11242.
4 The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4(3):e4825.
5 WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle. 2009 Sep 1;8(17):2769-78.
6 The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008 Sep 5;283(36):24478-83.
7 Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci USA. 2007 Jun 19;104(25):10394-9.
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 Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome. bioRxiv. 2021 Dec; DOI:.org/10.1101/2021.12.22.472458.
10 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.