Host Protein General Information (ID: PT0368)
  Protein Name
E3 ubiquitin/ISG15 ligase TRIM25 (TRIM25)
  Gene Name
TRIM25
  Host Species
Homo sapiens
  Uniprot Entry Name
TRI25_HUMAN
  EC Number
6.3.2.n3; 2.3.2.27
  Subcellular Location
Cytoplasm; Stress granule Nucleus
  External Link
NCBI Gene ID
7706
Uniprot ID
Q14258
Ensembl ID
ENSG00000121060
HGNC ID
HGNC:12932
  Function in Host
Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses bymediating ubiquitination of DDX58 and IFIH1. Mediates 'Lys-63'-linkedpolyubiquitination of the DDX58 N-terminal CARD-like region and mayplay a role in signal transduction that leads to the production ofinterferons in response to viral infection. Mediates 'Lys-63'-linked polyubiquitination of IFIH1. Promotes ISGylation of 14-3-3 sigma (SFN), anadapter protein implicated in the regulation of a large spectrumsignaling pathway. Mediates estrogenaction in various target organs. Mediates theubiquitination and subsequent proteasomal degradation of ZFHX3. Plays a role in promoting the restart of stalledreplication forks via interaction with the KHDC3L-OOEP scaffold andsubsequent ubiquitination of BLM, resulting in the recruitment andretainment of BLM at DNA replication forks. [1-4]
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  Related KEGG Pathway
RIG-I-like receptor signaling pathway hsa04622            Pathway Map 
Influenza A hsa05164            Pathway Map 
NF-kappa B signaling pathway hsa04064            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [5]
Infected TissueLung Infection Time24 h; 48 h
Infected CellCalu-3 cells (Human lung cancer cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein TRIM25 in viral infection, TRIM25 protein knockout Calu-3 cells were infected with SARS-COV-2 for 24 - 48 h , and the effects on infection was detected through qRT-PCR.
ResultsIt is reported that Knockdown of TRIM25 increases SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 5'-UTR (hCoV-19/South Korea/KCDC03/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              Strains Name
hCoV-19/South Korea/KCDC03/2020
              Strains Family
Alpha (B.1.1.7)
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Directly bind to SARS-CoV-23 RNA's 5' UTR region
              Infection Cells Vero cells (epithelial kidney cell)  (CVCL_0059 )
              Cell Originated Tissue kidney
              Infection Time 24 h
              Interaction Score P-adjust < 0.05
              Method Description Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/MS)
           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 [5]
              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)
              Infection Cells HCT-8 cells (Human ileocaecal adenocarcinoma cell) HCT-8 cells (Human ileocaecal adenocarcinoma cell)  (CVCL_2478 )
              Cell Originated Tissue Ileocecum
              Infection Time 12h; 24; 36h; 48h
              Interaction Score p_value < 0.05; FDR < 10%
              Method Description Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/MS)
           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 [6]
              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) Calu-3 cells (Human lung cancer cell)  (CVCL_0609 )
              Cell Originated Tissue Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.006
              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
P147 [7]
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S100 [7]
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S100 [8]
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S435 [8]
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T434 [8]
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Protein Sequence Information
MAELCPLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQGSPYLCPQCRAVYQARPQLHKNTVLCNVVEQFLQADLAREPPADVWTPPARASAPSPNAQVACDHCLKEAAVKTCLVCMASFCQEHLQPHFDSPAFQDHPLQPPVRDLLRRKCSQHNRLREFFCPEHSECICHICLVEHKTCSPASLSQASADLEATLRHKLTVMYSQINGASRALDDVRNRQQDVRMTANRKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNSKFDTIYQILLKKKSEIQTLKEEIEQSLTKRDEFEFLEKASKLRGISTKPVYIPEVELNHKLIKGIHQSTIDLKNELKQCIGRLQEPTPSSGDPGEHDPASTHKSTRPVKKVSKEEKKSKKPPPVPALPSKLPTFGAPEQLVDLKQAGLEAAAKATSSHPNSTSLKAKVLETFLAKSRPELLEYYIKVILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGPESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVFSAGATLSICSPK
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References
1 The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity by Inhibiting TRIM25 s RNA Binding Ability. mBio. 2021 Apr 13;12(2):e00620-21.
2 The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors. Immunity. 2018 Sep 18;49(3):438-448.e5.
3 A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog. 2013;9(8):e1003533.
4 TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007 Apr 19;446(7138):916-920.
5 The SARS-CoV-2 RNA interactome. Mol Cell. 2021 Jul 1;81(13):2838-2850.e6.
6 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.
7 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
8 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.