Details of Host Protein

 Host Protein General Information (ID: PT1034)
  Protein Name
Serine/threonine-protein kinase pim-1 (PIM1)
  Gene Name
PIM1
  Host Species
Homo sapiens
  Uniprot Entry Name
PIM1_HUMAN
  Protein Families
Protein kinase superfamily
  EC Number
2.7.11.1
  Subcellular Location
Cytoplasm
  External Link
NCBI Gene ID
5292
Uniprot ID
P11309
Ensembl ID
ENSG00000137193
HGNC ID
HGNC:8986
  Function in Host
Proto-oncogene with serine/threonine kinase activity involvedin cell survival and cell proliferation and thus providing a selectiveadvantage in tumorigenesis. Exerts its oncogenic activity through: theregulation of MYC transcriptional activity, the regulation of cellcycle progression and by phosphorylation and inhibition of proapoptoticproteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to anincrease of MYC protein stability and thereby an increase oftranscriptional activity. The stabilization of MYC exerted by PIM1might explain partly the strong synergism between these two oncogenesin tumorigenesis. Mediates survival signaling through phosphorylationof BAD, which induces release of the anti-apoptotic protein Bcl-X (L) /BCL2L1. Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibitsMAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequentlyreducing caspase-3 activation and cell apoptosis. Stimulates cell cycleprogression at the G1-S and G2-M transitions by phosphorylation ofCDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycleprogression at G1, results in the relocation of CDKN1A to the cytoplasmand enhanced CDKN1A protein stability. Promotes cell cycle progressionand tumorigenesis by down-regulating expression of a regulator of cellcycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B, induces 14-3-3proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylatingHP1 gamma/CBX3. Acts also as a regulator of homing and migration ofbone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis. Also phosphorylates and activates the ATP-bindingcassette transporter ABCG2, allowing resistance to drugs through theirexcretion from cells. Promotes brown adipocytedifferentiation. [1-8]
    Click to Show/Hide
  Related KEGG Pathway
JAK-STAT signaling pathway hsa04630            Pathway Map 
Pathways in cancer hsa05200            Pathway Map 
MicroRNAs in cancer hsa05206            Pathway Map 
Acute myeloid leukemia hsa05221            Pathway Map 
AGE-RAGE signaling pathway in diabetic complications hsa04933            Pathway Map 
  3D Structure
PDB ID: 1XQZ 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [9]
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 PIM1 in viral infection, PIM1 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 PIM1 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 3'-UTR (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [10]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score Prot score = 18
              Method Description RNA-protein interaction detection (RaPID) assay; liquid chromatography with tandem mass spectrometry (LC-MS/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  
Picture Not Found

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  
Picture Not Found

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  
Picture Not Found

Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
Fostamatinib DB12010  11671467  D0V8HJ  [11]
Triparanol . 58423153  D00IFR  [12]
Triparanol . 24795070  . [12]

Protein Sequence Information
MLLSKINSLAHLRAAPCNDLHATKLAPGKEKEPLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPNGTRVPMEVVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEELARSFFWQVLEAVRHCHNCGVLHRDIKDENILIDLNRGELKLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRWCLALRPSDRPTFEEIQNHPWMQDVLLPQETAEIHLHSLSPGPSK
    Click to Show/Hide

References
1 The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells. J Biol Chem. 2008 Feb 8;283(6):3349-3356.
2 PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis. Oncogene. 2009 Dec 3;28(48):4261-71.
3 Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res. 2008 Jul 1;68(13):5076-85.
4 The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C. Int J Biochem Cell Biol. 2006 Mar;38(3):430-43.
5 IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils. J Immunol. 2004 Nov 15;173(10):6409-17.
6 Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. Biochim Biophys Acta. 2002 Dec 16;1593(1):45-55.
7 Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1(1). FEBS Lett. 2000 Feb 4;467(1):17-21.
8 The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG. EMBO J. 1991 Mar;10(3):655-64.
9 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.
10 RNA-Protein Interaction Analysis of SARS-CoV-2 5 and 3 Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection. mSystems. 2021 Aug 31;6(4):e0064321.
11 DrugBank
12 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.