Details of Host Protein

 Host Protein General Information (ID: PT0915)
  Protein Name
Receptor of activated protein C kinase 1 (RACK1)
  Gene Name
RACK1
  Host Species
Homo sapiens
  Uniprot Entry Name
RACK1_HUMAN
  Protein Families
WD repeat G protein beta family
  Subcellular Location
Cell membrane
  External Link
NCBI Gene ID
10399
Uniprot ID
P63244
Ensembl ID
ENSG00000204842
HGNC ID
HGNC:4399
  Function in Host
Scaffolding protein involved in the recruitment, assemblyand/or regulation of a variety of signaling molecules. Interacts with awide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translationalrepression. Involved in the initiation of theribosome quality control (RQC), a pathway that takes place when aribosome has stalled during translation, by promoting ubiquitination ofa subset of 40S ribosomal subunits. Binds to andstabilizes activated protein kinase C (PKC), increasing PKC-mediatedphosphorylation. May recruit activated PKC to the ribosome, leading tophosphorylation of EIF6. Inhibits the activity of SRC kinases includingSRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phaseof the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA andinhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR followingPKC activation, represses AR transactivation activity and is requiredfor phosphorylation of AR by SRC. Modulates IGF1R-dependent integrinsignaling and promotes cell spreading and contact with theextracellular matrix. Involved in PKC-dependent translocation of ADAM12to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required forVANGL2 membrane localization, inhibits Wnt signaling, and regulatescellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulatesinternalization of the muscarinic receptor CHRM2. Promotes apoptosis byincreasing oligomerization of BAX and disrupting the interaction of BAXwith the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays arole in regulation of FLT1-mediated cell migration. Involved in thetransport of ABCB4 from the Golgi to the apical bile canalicularmembrane. Promotes migration of breast carcinomacells by binding to and activating RHOA. [1-21]
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  Related KEGG Pathway
Measles hsa05162            Pathway Map 
  3D Structure
PDB ID: 4AOW 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [22]
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 RACK1 in viral infection, RACK1 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 RACK1 leads to the decreased 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: Not Specified Virus Region (hCoV-19/USA/WA1/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [23]
              Strains Name
hCoV-19/USA/WA1/2020
              Strains Family
Alpha (B.1.1.7)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7.5 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_7927 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score FDR ≤ 0.05
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           RNA Region: Not Specified Virus Region (hCoV-19/France/IDF-220-95/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [24]
              Strains Name
hCoV-19/France/IDF-220-95/2020
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Direct interaction
              Infection Cells HEK293 Cells (Human embryonic kidney cell) HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Kidney
              Infection Time 48 h
              Interaction Score SAINT score ≥ 0.79
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-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
  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
T316 [25]
  PNG Download  
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T316 [26]
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Protein Sequence Information
MTEQMTLRGTLKGHNGWVTQIATTPQFPDMILSASRDKTIIMWKLTRDETNYGIPQRALRGHSHFVSDVVISSDGQFALSGSWDGTLRLWDLTTGTTTRRFVGHTKDVLSVAFSSDNRQIVSGSRDKTIKLWNTLGVCKYTVQDESHSEWVSCVRFSPNSSNPIIVSCGWDKLVKVWNLANCKLKTNHIGHTGYLNTVTVSPDGSLCASGGKDGQAMLWDLNEGKHLYTLDGGDIINALCFSPNRYWLCAATGPSIKIWDLEGKIIVDELKQEVISTSSKAEPPQCTSLAWSADGQTLFAGYTDNLVRVWQVTIGTR
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References
1 RACK1, a new ADAM12 interacting protein Contribution to liver fibrogenesis. J Biol Chem. 2008 Sep 19;283(38):26000-9.
2 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation. Mol Cell. 2017 Feb 16;65(4):751-760.e4.
3 Structures of the human and Drosophila 80S ribosome. Nature. 2013 May 2;497(7447):80-5.
4 RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. J Biol Chem. 2011 Mar 18;286(11):9097-106.
5 The RACK1 signaling scaffold protein selectively interacts with Yersinia pseudotuberculosis virulence function. PLoS One. 2011 Feb 10;6(2):e16784.
6 RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway. Breast Cancer Res Treat. 2011 Apr;126(3):555-63.
7 RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl-XL. Cell Signal. 2010 Oct;22(10):1495-501.
8 RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. PLoS One. 2010 Oct 20;5(10):e13517.
9 A stimulatory role for the La-related protein 4B in translation. RNA. 2010 Aug;16(8):1488-99.
10 Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4. Hepatol Res. 2009 Nov;39(11):1091-107.
11 Phosphorylation of RACK1 on tyrosine 52 by c-Abl is required for insulin-like growth factor I-mediated regulation of focal adhesion kinase. J Biol Chem. 2009 Jul 24;284(30):20263-74.
12 RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation. Biochem Biophys Res Commun. 2009 Dec 11;390(2):217-22.
13 RACK1 regulates the cell surface expression of the G protein-coupled receptor for thromboxane A(2). Traffic. 2008 Mar;9(3):394-407.
14 RACK1 inhibits TRPM6 activity via phosphorylation of the fused alpha-kinase domain. Curr Biol. 2008 Feb 12;18(3):168-76.
15 Interaction of integrin beta1 with cytokeratin 1 in neuroblastoma NMB7 cells. Biochem Soc Trans. 2007 Nov;35(Pt 5):1292-4.
16 RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Mol Cell. 2007 Jan 26;25(2):207-17.
17 Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor. Cancer Res. 2006 Nov 15;66(22):11047-54.
18 The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. J Biol Chem. 2003 Nov 14;278(46):46087-93.
19 RACK1 regulates integrin-mediated adhesion, protrusion, and chemotactic cell migration via its Src-binding site. Mol Biol Cell. 2003 Feb;14(2):658-69.
20 RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002 Apr;22(7):2345-65.
21 RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells. Mol Cell Biol. 1998 Jun;18(6):3245-56.
22 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.
23 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
24 Characterization and functional interrogation of the SARS-CoV-2 RNA interactome. Cell Rep. 2022 Apr 26;39(4):110744.
25 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
26 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.