Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0137)
DME Name Thymidylate synthase (TYMS), Homo sapiens DME Info
UniProt ID
TYSY_HUMAN
EC Number    EC: 2.1.1.45     (Click to Show/Hide the Complete EC Tree)
Transferase
Methylase
Methyltransferase
EC: 2.1.1.45
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
                     Oligomerization
                            Dihydrofolate reductase (DHFR) Health Homodimer
Uniprot ID
DYR_HUMAN
Interaction Name DHFR-TYMS homodimerization [1]
Studied Cell Lines Escherichia coli cells
Description Dihydrofolate reductase (DHFR) is reported to homodimerize with the TYMS gene, which is necessary for sustaining the enzyme activity of Thymidylate synthase. As a result, the interaction between DHFR and TYMS is necessary for sustaining the drug-metabolizing process of Thymidylate synthase.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2B71 Gastric cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Histone modification
                            Histone deacetylase 6 (HDAC6) Gastric cancer Repression
Uniprot ID
HDAC6_HUMAN
Interaction Name HDAC6-TYMS interaction [2]
Studied Cell Lines Gastric cancer cells
Description Histone deacetylase 6 (HDAC6) is reported to deacetylate the TYMS gene and thereby represses the transcriptional activity of the drug-metabolizing enzyme Thymidylate synthase. As a result, the interaction between HDAC6 and TYMS can inhibit the drug-metabolizing process of Thymidylate synthase.
               ICD-11: 2B90 Colorectal cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-203a-3p Colorectal cancer Suppression
miRBase ID
MIMAT0000264
Interaction Name hsa-miR-203a-3p--TYMS regulation [3]
Studied Cell Lines HCT116, Caco2 and SW480 cell lines
Description hsa-miR-203a-3p is reported to suppress TYMS mRNA translation by binding to the 3' untranslated region (3'UTR) of TYMS mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase.
               ICD-11: 2C12 Liver cancer Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                     Transcription-factor regulation
                            TF factor Dp-1 (TFDP1) Liver cancer Activation
Uniprot ID
TFDP1_HUMAN
Interaction Name TFDP1-TYMS interaction [4]
Studied Cell Lines Hep3B cell line
Ensembl ID
ENSG00000198176
Description TF factor Dp-1 (TFDP1) is reported to activate the transcription of TYMS gene, which leads to an increased expression of the drug-metabolizing enzyme Thymidylate synthase. As a result, the interaction between TFDP1 and TYMS can activate the drug-metabolizing process of Thymidylate synthase.
                            TF factor E2F1 (E2F1) Liver cancer Activation
Uniprot ID
E2F1_HUMAN
Interaction Name E2F1-TYMS interaction [4], [5]
Studied Cell Lines Hep3B cell line
Ensembl ID
ENSG00000101412
Description TF factor E2F1 (E2F1) is reported to activate the transcription of TYMS gene, which leads to an increased expression of the drug-metabolizing enzyme Thymidylate synthase. As a result, the interaction between E2F1 and TYMS can activate the drug-metabolizing process of Thymidylate synthase.
               ICD-11: 2C26 Pleural mesothelioma Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-193a-3p Malignant pleural mesothelioma Suppression
miRBase ID
MIMAT0000459
Interaction Name hsa-miR-193a-3p--TYMS regulation [6]
Studied Cell Lines H28, H2052 and H2452 cell lines
Description hsa-miR-193a-3p is reported to suppress TYMS mRNA translation by binding to the 3' untranslated region (3'UTR) of TYMS mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase.
               ICD-11: 2C73 Ovarian cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Transcription-factor regulation
                            Y-box-binding protein 1 (YBX1) Ovarian cancer Repression
Uniprot ID
YBOX1_HUMAN
Interaction Name YBX1-TYMS interaction [7]
Studied Cell Lines OVCAR-3 and SKOV-3 cell lines
Ensembl ID
ENSG00000065978
Description Y-box-binding protein 1 (YBX1) is reported to repress the transcription of TYMS gene, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase. As a result, the interaction between YBX1 and TYMS can repress the drug-metabolizing process of Thymidylate synthase.
               ICD-11: 2C77 Cervical cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-433-3p Cervical cancer Suppression
miRBase ID
MIMAT0001627
Interaction Name hsa-miR-433-3p--TYMS regulation [8]
Studied Cell Lines HeLa cell line
Description hsa-miR-433-3p is reported to suppress TYMS mRNA translation by binding to the 3' untranslated region (3'UTR) of TYMS mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase.
               ICD-11: 2C82 Prostate cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Transcription-factor regulation
                            Tumor suppressor p53 (TP53) Prostate cancer Repression
Uniprot ID
P53_HUMAN
Interaction Name TP53-TYMS interaction [9]
Studied Cell Lines LNCaP, C4-2 and PC3 cell lines
Ensembl ID
ENSG00000141510
Description Tumor suppressor p53 (TP53) is reported to repress the transcription of TYMS gene, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase. As a result, the interaction between TP53 and TYMS can repress the drug-metabolizing process of Thymidylate synthase.
               ICD-11: 2C90 Renal cell carcinoma Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-196a-5p Renal cell carcinoma Suppression
miRBase ID
MIMAT0000226
Interaction Name hsa-miR-196a-5p--TYMS regulation [10]
Studied Cell Lines Renal cell carcinoma cell line
Description hsa-miR-196a-5p is reported to suppress TYMS mRNA translation by binding to the 3' untranslated region (3'UTR) of TYMS mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Thymidylate synthase.
References
1 Essential protein-protein interactions between Plasmodium falciparum thymidylate synthase and dihydrofolate reductase domains. J Biol Chem. 1999 Dec 31;274(53):37781-6.
2 Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells. Br J Cancer. 2017 Mar 28;116(7):903-911.
3 miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncol Rep. 2015 Feb;33(2):607-14.
4 Association of over-expressed TFDP1 with progression of hepatocellular carcinomas. J Hum Genet. 2003;48(12):609-613.
5 UCN-01 suppresses thymidylate synthase gene expression and enhances 5-fluorouracil-induced apoptosis in a sequence-dependent manner. Clin Cancer Res. 1998 Sep;4(9):2201-6.
6 miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma. Oncotarget. 2015 Sep 15;6(27):23480-95.
7 Akt-dependent Nuclear Localization of Y-box-binding Protein 1 in Acquisition of Malignant Characteristics by Human Ovarian Cancer Cells. Oncogene. 2007 Apr 26;26(19):2736-46.
8 MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells. BMC Cancer. 2013 Aug 2;13:369.
9 Low-dose docetaxel enhances the sensitivity of S-1 in a xenograft model of human castration eesistant prostate cancer. Int J Cancer. 2012 Jan 15;130(2):431-42.
10 Genetic variations in microRNAs and the risk and survival of renal cell cancer. Carcinogenesis. 2014 Jul;35(7):1629-35.

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