Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0141)
DME Name Dihydrofolate reductase (DHFR), Homo sapiens DME Info
UniProt ID
DYR_HUMAN
EC Number    EC: 1.5.1.3     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.3
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:        2 HOSPPI
                     Oligomerization
                            Thymidylate synthase (TYMS) Health Homodimer
Uniprot ID
TYSY_HUMAN
Interaction Name TYMS-DHFR homodimerization [2]
Studied Cell Lines Escherichia coli cells
Description Thymidylate synthase (TYMS) is reported to homodimerize with the DHFR gene, which is necessary for sustaining the enzyme activity of Dihydrofolate reductase. As a result, the interaction between TYMS and DHFR is necessary for sustaining the drug-metabolizing process of Dihydrofolate reductase.
                     Non-coding RNA regulation
                            hsa-miR-24-3p Health Suppression
miRBase ID
MIMAT0000080
Interaction Name hsa-miR-24-3p--DHFR regulation [1]
Studied Cell Lines CHO DG44 cell line
Description hsa-miR-24-3p is reported to suppress DHFR mRNA translation by binding to the 3' untranslated region (3'UTR) of DHFR mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Dihydrofolate reductase.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2A00 Brain cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-192-5p Medulloblastoma Suppression
miRBase ID
MIMAT0000222
Interaction Name hsa-miR-192-5p--DHFR regulation [3]
Studied Cell Lines D283 cell line
Description hsa-miR-192-5p is reported to suppress DHFR mRNA translation by binding to the 3' untranslated region (3'UTR) of DHFR mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Dihydrofolate reductase.
               ICD-11: 2B51 Osteosarcoma Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Transcription-factor regulation
                            Retinoblastoma-associated (RB1) Osteosarcoma Repression
Uniprot ID
RB_HUMAN
Interaction Name RB1-DHFR interaction [4]
Studied Cell Lines SAOS and MCF-10A cell lines
Description Retinoblastoma-associated (RB1) is reported to repress the transcription of DHFR gene, which leads to a decreased expression of the drug-metabolizing enzyme Dihydrofolate reductase. As a result, the interaction between RB1 and DHFR can repress the drug-metabolizing process of Dihydrofolate reductase.
               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-DHFR interaction [5]
Studied Cell Lines Hep3B cell line
Ensembl ID
ENSG00000198176
Description TF factor Dp-1 (TFDP1) is reported to activate the transcription of DHFR gene, which leads to an increased expression of the drug-metabolizing enzyme Dihydrofolate reductase. As a result, the interaction between TFDP1 and DHFR can activate the drug-metabolizing process of Dihydrofolate reductase.
                            TF factor E2F1 (E2F1) Liver cancer Activation
Uniprot ID
E2F1_HUMAN
Interaction Name E2F1-DHFR interaction [5]
Studied Cell Lines Hep3B cell line
Ensembl ID
ENSG00000101412
Description TF factor E2F1 (E2F1) is reported to activate the transcription of DHFR gene, which leads to an increased expression of the drug-metabolizing enzyme Dihydrofolate reductase. As a result, the interaction between E2F1 and DHFR can activate the drug-metabolizing process of Dihydrofolate reductase.
               ICD-11: 2C60 Breast cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Non-coding RNA regulation
                            hsa-miR-25-3p Breast cancer Suppression
miRBase ID
MIMAT0000081
Interaction Name hsa-miR-25-3p--DHFR regulation [6]
Studied Cell Lines MCF-7 cell line
Description hsa-miR-25-3p is reported to suppress DHFR mRNA translation by binding to the 3' untranslated region (3'UTR) of DHFR mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Dihydrofolate reductase.
References
1 A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13513-8.
2 Essential protein-protein interactions between Plasmodium falciparum thymidylate synthase and dihydrofolate reductase domains. J Biol Chem. 1999 Dec 31;274(53):37781-6.
3 miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47. Oncotarget. 2015 Dec 22;6(41):43712-30.
4 Regulation of cellular genes in a chromosomal context by the retinoblastoma tumor suppressor protein. Mol Cell Biol. 1998 Aug;18(8):4565-76.
5 Association of over-expressed TFDP1 with progression of hepatocellular carcinomas. J Hum Genet. 2003;48(12):609-613.
6 A-to-I RNA Editing Up-regulates Human Dihydrofolate Reductase in Breast Cancer. J Biol Chem. 2017 Mar 24;292(12):4873-4884.

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