Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0154)
DME Name	Asparagine synthetase (ASNS), Homo sapiens	DME Info
UniProt ID	ASNS_HUMAN
EC Number	EC: 6.3.5.4 (Click to Show/Hide the Complete EC Tree) Ligase Carbon-nitrogen ligase Carbon-nitrogen ligase EC: 6.3.5.4
Lineage	Species: Homo sapiens (Click to Show/Hide the Complete Species Lineage) Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens
Interactome

Disease Specific Interactions between Host Protein and DME (HOSPPI)
ICD Disease Classification Healthy
ICD-11: Healthy		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
C/EBP-homologous protein (DDIT3)		Health		Repression
Uniprot ID	DDIT3_HUMAN
Interaction Name	DDIT3-ASNS interaction				[1]
Studied Cell Lines	HEK 293T cell line
Ensembl ID	ENSG00000175197
Description	C/EBP-homologous protein (DDIT3) is reported to repress the transcription of ASNS gene, which leads to a decreased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between DDIT3 and ASNS can repress the drug-metabolizing process of Asparagine synthetase.
ICD Disease Classification 01 Infectious/parasitic diseases
ICD-11: 1F57 Toxoplasma gondii infection		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Toxoplasma gondii infection		Moderate hypermethylation
Interaction Name	DNMT-ASNS interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypermethylation p-value: 7.89E-03; delta-beta: 2.96E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hyper-methylate the ASNS gene, which leads to a moderatly decreased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between DNMT and ASNS can moderatly affect the drug-metabolizing process of Asparagine synthetase.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual
ICD Disease Classification 02 Neoplasms
ICD-11: 2A00 Brain cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Brain neuroblastoma		Moderate hypomethylation
Interaction Name	DNMT-ASNS interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypomethylation p-value: 1.30E-13; delta-beta: -2.48E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the ASNS gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between DNMT and ASNS can moderatly affect the drug-metabolizing process of Asparagine synthetase.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual
ICD-11: 2B90 Colorectal cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
WW-containing regulator 1 (WWTR1)		Colorectal cancer		Repression
Uniprot ID	WWTR1_HUMAN
Interaction Name	WWTR1-ASNS interaction				[2]
Studied Cell Lines	RKO and HCT116 cell lines
Description	WW-containing regulator 1 (WWTR1) is reported to repress the transcription of ASNS gene, which leads to a decreased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between WWTR1 and ASNS can repress the drug-metabolizing process of Asparagine synthetase.
ICD-11: 2C12 Liver cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Activating TF factor 3 (ATF3)		Liver cancer		Activation
Uniprot ID	ATF3_HUMAN
Interaction Name	ATF3-ASNS interaction				[3]
Studied Cell Lines	HepG2 cell line
Ensembl ID	ENSG00000162772
Description	Activating TF factor 3 (ATF3) is reported to activate the transcription of ASNS gene, which leads to an increased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between ATF3 and ASNS can activate the drug-metabolizing process of Asparagine synthetase.
Activating TF factor 4 (ATF4)		Liver cancer		Activation
Uniprot ID	ATF4_HUMAN
Interaction Name	ATF4-ASNS interaction				[4], [5], [6]
Studied Cell Lines	HepG2 cell line
Ensembl ID	ENSG00000128272
Description	Activating TF factor 4 (ATF4) is reported to activate the transcription of ASNS gene, which leads to an increased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between ATF4 and ASNS can activate the drug-metabolizing process of Asparagine synthetase.
ICD-11: 2D50 Brain cancer metastasis		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Esthesioneuroblastoma		Moderate hypomethylation
Interaction Name	DNMT-ASNS interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypomethylation p-value: 1.39E-06; delta-beta: -2.09E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the ASNS gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Asparagine synthetase. As a result, the interaction between DNMT and ASNS can moderatly affect the drug-metabolizing process of Asparagine synthetase.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual

References
1	C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem. 2008 Dec 12;283(50):35106-17.
2	Lentivirus-mediated RNA interference targeting WWTR1 in human colorectal cancer cells inhibits cell proliferation in vitro and tumor growth in vivo. Oncol Rep. 2012 Jul;28(1):179-85.
3	Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter. J Biol Chem. 2003 Oct 3;278(40):38402-12.
4	ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem. 2002 Jul 5;277(27):24120-7.
5	Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP. Biol Chem. 2005 Sep;386(9):873-9.
6	CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. Mitochondrion. 2007 Feb-Apr;7(1-2):80-8.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.