Host Protein General Information (ID: PT0225)
  Protein Name
Inosine 5'-monophosphate cyclohydrolase (IMP cyclohydrolase)
  Gene Name
ATIC
  Host Species
Homo sapiens
  Uniprot Entry Name
PUR9_HUMAN
  Protein Families
PurH family
  EC Number
2.1.2.3; 3.5.4.1.
  External Link
NCBI Gene ID
471
Uniprot ID
P31939
Ensembl ID
ENSG00000138363
HGNC ID
HGNC:794
  Function in Host
Bifunctional enzyme that catalyzes the last two steps ofpurine biosynthesis. Acts as atransformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1- (5-phospho-beta-D-ribosyl) imidazole-4-carboxamide) toproduce the intermediate formyl-AICAR (FAICAR). Can use both 10-formyldihydrofolateand 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis usedin the treatment of human leukemias. Promotes insulinreceptor/INSR autophosphorylation and is involved in INSRinternalization. [1-4]
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  Related KEGG Pathway
Antifolate resistance hsa01523            Pathway Map 
Metabolic pathways hsa01100            Pathway Map 
One carbon pool by folate hsa00670            Pathway Map 
Purine metabolism hsa00230            Pathway Map 
  3D Structure

Host Protein - Virus RNA Network

 Full List of Virus RNA Interacting with This Protien
            RNA Region: ORF10 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
ORF10
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (human liver cell line)  (CVCL_0336 )
              Cell Originated Tissue Liver
              Interaction Score P-value < 0.05
              Method Description RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)
           RNA Region: 5'-UTR of ORF6 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
5'-UTR of ORF6
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (human liver cell line); Calu-3 cells (human lung cancer cell line) Huh7 cells (human liver cell line); Calu-3 cells (human lung cancer cell line)  (CVCL_0336;CVCL_0609 )
              Cell Originated Tissue Liver; Lung
              Interaction Score P-value < 0.05
              Method Description RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)
           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 [6]
              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) 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 Sequence Information
MAPGQLALFSVSDKTGLVEFARNLTALGLNLVASGGTAKALRDAGLAVRDVSELTGFPEMLGGRVKTLHPAVHAGILARNIPEDNADMARLDFNLIRVVACNLYPFVKTVASPGVTVEEAVEQIDIGGVTLLRAAAKNHARVTVVCEPEDYVVVSTEMQSSESKDTSLETRRQLALKAFTHTAQYDEAISDYFRKQYSKGVSQMPLRYGMNPHQTPAQLYTLQPKLPITVLNGAPGFINLCDALNAWQLVKELKEALGIPAAASFKHVSPAGAAVGIPLSEDEAKVCMVYDLYKTLTPISAAYARARGADRMSSFGDFVALSDVCDVPTAKIISREVSDGIIAPGYEEEALTILSKKKNGNYCVLQMDQSYKPDENEVRTLFGLHLSQKRNNGVVDKSLFSNVVTKNKDLPESALRDLIVATIAVKYTQSNSVCYAKNGQVIGIGAGQQSRIHCTRLAGDKANYWWLRHHPQVLSMKFKTGVKRAEISNAIDQYVTGTIGEDEDLIKWKALFEEVPELLTEAEKKEWVEKLTEVSISSDAFFPFRDNVDRAKRSGVAYIAAPSGSAADKVVIEACDELGIILAHTNLRLFHH
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References
1 The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5 -monophosphate cyclohydrolase) A surprising lack of substrate channeling. J Biol Chem. 2002 Jun 21;277(25):22168-74.
2 Catalytic mechanism of the cyclohydrolase activity of human aminoimidazole carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase. Biochemistry. 2004 Feb 10;43(5):1184-92.
3 Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding and catalysis. Biochemistry. 2000 Sep 19;39(37):11303-11.
4 Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase. J Biochem. 1997 Aug;122(2):309-13.
5 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
6 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.