Details of Host Protein

 Host Protein General Information (ID: PT1219)
  Protein Name
UDP-glucose 6-dehydrogenase (UGDH)
  Gene Name
UGDH
  Host Species
Homo sapiens
  Uniprot Entry Name
UGDH_HUMAN
  Protein Families
UDP-glucose/GDP-mannose dehydrogenase family
  EC Number
1.1.1.22
  External Link
NCBI Gene ID
7358
Uniprot ID
O60701
Ensembl ID
ENSG00000109814
HGNC ID
HGNC:12525
  Function in Host
Catalyzes the formation of UDP-alpha-D-glucuronate, aconstituent of complex glycosaminoglycans . Required for thebiosynthesis of chondroitin sulfate and heparan sulfate. Required forembryonic development via its role in the biosynthesis ofglycosaminoglycans. Required for proper brain andneuronal development. [1-9]
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  Related KEGG Pathway
Pentose and glucuronate interconversions hsa00040            Pathway Map 
Ascorbate and aldarate metabolism hsa00053            Pathway Map 
Amino sugar and nucleotide sugar metabolism hsa00520            Pathway Map 
Metabolic pathways hsa01100            Pathway Map 
Biosynthesis of cofactors hsa01240            Pathway Map 
Biosynthesis of nucleotide sugars hsa01250            Pathway Map 
Pentose and glucuronate interconversions hsa00040            Pathway Map 
Ascorbate and aldarate metabolism hsa00053            Pathway Map 
Amino sugar and nucleotide sugar metabolism hsa00520            Pathway Map 
Metabolic pathways hsa01100            Pathway Map 
Biosynthesis of cofactors hsa01240            Pathway Map 
Biosynthesis of nucleotide sugars hsa01250            Pathway Map 
  3D Structure
PDB ID: 2Q3E 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [10]
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 UGDH in viral infection, UGDH 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 UGDH leads to the decreased SARS-CoV-2 RNA levels compared with control group.

 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 [11]
              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)

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
S47 [12]
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S476 [12]
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T91 [12]
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T93 [12]
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Protein Sequence Information
MFEIKKICCIGAGYVGGPTCSVIAHMCPEIRVTVVDVNESRINAWNSPTLPIYEPGLKEVVESCRGKNLFFSTNIDDAIKEADLVFISVNTPTKTYGMGKGRAADLKYIEACARRIVQNSNGYKIVTEKSTVPVRAAESIRRIFDANTKPNLNLQVLSNPEFLAEGTAIKDLKNPDRVLIGGDETPEGQRAVQALCAVYEHWVPREKILTTNTWSSELSKLAANAFLAQRISSINSISALCEATGADVEEVATAIGMDQRIGNKFLKASVGFGGSCFQKDVLNLVYLCEALNLPEVARYWQQVIDMNDYQRRRFASRIIDSLFNTVTDKKIAILGFAFKKDTGDTRESSSIYISKYLMDEGAHLHIYDPKVPREQIVVDLSHPGVSEDDQVSRLVTISKDPYEACDGAHAVVICTEWDMFKELDYERIHKKMLKPAFIFDGRRVLDGLHNELQTIGFQIETIGKKVSSKRIPYAPSGEIPKFSLQDPPNKKPKV
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References
1 Cofactor binding triggers a molecular switch to allosterically activate human UDP-a-D-glucose 6-dehydrogenase. Biochemistry. 2012 Nov 20;51(46):9364-74.
2 Conformational flexibility in the allosteric regulation of human UDP-a-D-glucose 6-dehydrogenase. Biochemistry. 2011 Nov 8;50(44):9651-63.
3 Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy. Nat Commun. 2020 Jan 30;11(1):595.
4 The entropic force generated by intrinsically disordered segments tunes protein function. Nature. 2018 Nov;563(7732):584-588.
5 Hysteresis and Allostery in Human UDP-Glucose Dehydrogenase Require a Flexible Protein Core. Biochemistry. 2018 Dec 18;57(50):6848-6859.
6 Allostery and Hysteresis Are Coupled in Human UDP-Glucose Dehydrogenase. Biochemistry. 2017 Jan 10;56(1):202-211.
7 Hysteresis in human UDP-glucose dehydrogenase is due to a restrained hexameric structure that favors feedback inhibition. Biochemistry. 2014 Dec 30;53(51):8043-51.
8 Structural and kinetic evidence that catalytic reaction of human UDP-glucose 6-dehydrogenase involves covalent thiohemiacetal and thioester enzyme intermediates. J Biol Chem. 2012 Jan 13;287(3):2119-29.
9 Structure and mechanism of human UDP-glucose 6-dehydrogenase. J Biol Chem. 2011 Jul 8;286(27):23877-87.
10 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.
11 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
12 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.