Details of Host Protein

 Host Protein General Information (ID: PT1019)
  Protein Name
Serine hydroxymethyltransferase (SHMT2)
  Gene Name
SHMT2
  Host Species
Homo sapiens
  Uniprot Entry Name
GLYM_HUMAN
  Protein Families
SHMT family
  EC Number
2.1.2.1
  Subcellular Location
Nucleus; cytoplasm and cytosol
  External Link
NCBI Gene ID
6472
Uniprot ID
P34897
Ensembl ID
ENSG00000182199
HGNC ID
HGNC:10852
  Function in Host
Catalyzes the cleavage of serine to glycine accompanied withthe production of 5, 10-methylenetetrahydrofolate, an essentialintermediate for purine biosynthesis. Serine provides themajor source of folate one-carbon in cells by catalyzing the transferof one carbon from serine to tetrahydrofolate. Contributes to the de novo mitochondrial thymidylate biosynthesispathway via its role in glycine and tetrahydrofolate metabolism:thymidylate biosynthesis is required to prevent uracil accumulation inmtDNA. Also required for mitochondrial translation byproducing 5, 10-methylenetetrahydrofolate; 5, 10-methylenetetrahydrofolate providing methyl donors to produce thetaurinomethyluridine base at the wobble position of some mitochondrialtRNAs. Associates with mitochondrialDNA. In addition to its role in mitochondria, alsoplays a role in the deubiquitination of target proteins as component ofthe BRISC complex: required for IFNAR1 deubiquitination by the BRISCcomplex. [1-6]
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  Related KEGG Pathway
Biosynthesis of cofactors hsa01240            Pathway Map 
Glycine, serine and threonine metabolism hsa00260            Pathway Map 
Glyoxylate and dicarboxylate metabolism hsa00630            Pathway Map 
Antifolate resistance hsa01523            Pathway Map 
Metabolic pathways hsa01100            Pathway Map 
Carbon metabolism hsa01200            Pathway Map 
Biosynthesis of amino acids hsa01230            Pathway Map 
One carbon pool by folate hsa00670            Pathway Map 
  3D Structure
PDB ID: 4PVF 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [7]
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 SHMT2 in viral infection, SHMT2 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 SHMT2 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/IPBCAMS-YL01/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [8]
              Strains Name
hCoV-19/IPBCAMS-YL01/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Unlikely to be direct binder
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score MIST = 0.876405885
              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
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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
S266 [9]
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S266 [10]
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Protein Sequence Information
MLYFSLFWAARPLQRCGQLVRMAIRAQHSNAAQTQTGEANRGWTGQESLSDSDPEMWELLQREKDRQCRGLELIASENFCSRAALEALGSCLNNKYSEGYPGKRYYGGAEVVDEIELLCQRRALEAFDLDPAQWGVNVQPYSGSPANLAVYTALLQPHDRIMGLDLPDGGHLTHGYMSDVKRISATSIFFESMPYKLNPKTGLIDYNQLALTARLFRPRLIIAGTSAYARLIDYARMREVCDEVKAHLLADMAHISGLVAAKVIPSPFKHADIVTTTTHKTLRGARSGLIFYRKGVKAVDPKTGREIPYTFEDRINFAVFPSLQGGPHNHAIAAVAVALKQACTPMFREYSLQVLKNARAMADALLERGYSLVSGGTDNHLVLVDLRPKGLDGARAERVLELVSITANKNTCPGDRSAITPGGLRLGAPALTSRQFREDDFRRVVDFIDEGVNIGLEVKSKTAKLQDFKSFLLKDSETSQRLANLRQRVEQFARAFPMPGFDEH
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References
1 How pyridoxal 5 -phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state. FEBS J. 2015 Apr;282(7):1225-41.
2 Impairment of the mitochondrial one-carbon metabolism enzyme SHMT2 causes a novel brain and heart developmental syndrome. Acta Neuropathol. 2020 Dec;140(6):971-975.
3 Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs. Mol Cell. 2018 Feb 15;69(4):610-621.e5.
4 Mitochondrial translation requires folate-dependent tRNA methylation. Nature. 2018 Feb 1;554(7690):128-132.
5 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. 2013 Oct 17;5(1):180-93.
6 Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci USA. 2011 Sep 13;108(37):15163-8.
7 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.
8 Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. Cell Res. 2022 Jan;32(1):9-23.
9 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
10 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.