MPL
Summary: In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008].
Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
---|---|---|---|---|---|
MPL proto-oncogene, thrombopoietin receptor | MIM:159530 | Ensembl:ENSG00000117400 | HGNC:HGNC:7217 | PA30923 | 1p34.2 |
GO terms in MPL
Term Type | Evidence Type | GO Term ID | GO Des. |
---|---|---|---|
MF | TAS | GO:0004888 | transmembrane signaling receptor activity |
MF | IPI | GO:0005515 | protein binding |
MF | IMP | GO:0038164 | thrombopoietin receptor activity |
CC | IDA | GO:0005794 | Golgi apparatus |
CC | TAS | GO:0005886 | plasma membrane |
CC | TAS | GO:0005887 | integral component of plasma membrane |
CC | IDA | GO:0009986 | cell surface |
CC | IEA | GO:0043005 | neuron projection |
CC | IEA | GO:0043025 | neuronal cell body |
BP | IEA | GO:0001780 | neutrophil homeostasis |
BP | TAS | GO:0007166 | cell surface receptor signaling pathway |
BP | TAS | GO:0008283 | cell proliferation |
BP | IEA | GO:0035702 | monocyte homeostasis |
BP | IEA | GO:0038163 | thrombopoietin-mediated signaling pathway |
BP | IEA | GO:0050671 | positive regulation of lymphocyte proliferation |
BP | IEA | GO:0070527 | platelet aggregation |
BP | IEA | GO:0071456 | cellular response to hypoxia |
BP | IEA | GO:1905221 | positive regulation of platelet formation |
BP | IEA | GO:1990959 | eosinophil homeostasis |
BP | IEA | GO:1990960 | basophil homeostasis |
Gene expression in normal tissue: MPL
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MPL
Database | Pathway ID | Pathway Des. |
---|---|---|
kegg | hsa04060 | Cytokine-cytokine receptor interaction - Homo sapiens (human) |
kegg | hsa04630 | Jak-STAT signaling pathway - Homo sapiens (human) |
biocarta | tpopathway | tpo signaling pathway |
reactome | R-HSA-109582 | Hemostasis |
reactome | R-HSA-76002 | Platelet activation, signaling and aggregation |
reactome | R-HSA-76009 | Platelet Aggregation (Plug Formation) |
Gene-Drug: Aster Plot
Drug ID | Drug Name | Model Num. |
---|---|---|
iGMDRD802 | 4-methylfasudil | 6 |
iGMDRD137 | Indisulam | 4 |
iGMDRD870 | BRD63610 | 2 |
iGMDRD171 | Pemetrexed | 5 |
iGMDRD506 | Fedratinib | 4 |
iGMDRD329 | Merck60 | 3 |
iGMDRD74 | Idarubicin | 3 |
iGMDRD887 | Compound 23 citrate | 3 |
iGMDRD100 | Zebularine | 5 |
iGMDRD451 | Serdemetan | 3 |
iGMDRD23 | Gossypol | 5 |
iGMDRD60 | Quinoclamine | 3 |
iGMDRD64 | Parbendazole | 3 |
iGMDRD932 | JAK inhibitor | 2 |
iGMDRD772 | BRD4770 | 5 |
iGMDRD584 | VER 155008 | 5 |
iGMDRD607 | Ubistatin B | 5 |
iGMDRD126 | Tipifarnib | 3 |
iGMDRD781 | Sirolimus | 3 |
iGMDRD405 | PIK-75 | 3 |
iGMDRD193 | Fqi1 | 3 |
iGMDRD280 | CYTOCHALASIN B | 6 |
iGMDRD123 | Isoevodiamine | 3 |
iGMDRD901 | ELCPK | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MPL