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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]
MPL (MPL Proto-Oncogene, Thrombopoietin Receptor) is a Protein Coding gene. Diseases associated with MPL include Myelofibrosis and Amegakaryocytic Thrombocytopenia, Congenital. Among its related pathways are PEDF Induced Signaling and Hematopoietic Stem Cells and Lineage-specific Markers. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and thrombopoietin receptor activity. An important paralog of this gene is EPOR.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004896 | cytokine receptor activity | IEA | -- |
GO:0005515 | protein binding | IEA,IPI | 24931576 |
GO:0038164 | thrombopoietin receptor activity | IMP | 25538044 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005794 | Golgi apparatus | IEA,IDA | 25538044 |
GO:0005886 | plasma membrane | IDA,TAS | -- |
GO:0009986 | cell surface | IEA,IDA | 25538044 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Response to elevated platelet cytosolic Ca2+ |
.44
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2 | NF-kappaB Signaling | ||
3 | PEDF Induced Signaling | ||
4 | JAK-STAT signaling pathway | ||
5 | Hematopoietic Stem Cells and Lineage-specific Markers |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001780 | neutrophil homeostasis | IEA | -- |
GO:0019221 | cytokine-mediated signaling pathway | IEA | -- |
GO:0035702 | monocyte homeostasis | IEA | -- |
GO:0038163 | thrombopoietin-mediated signaling pathway | IEA | -- |
GO:0050671 | positive regulation of lymphocyte proliferation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Eltrombopag | Approved | Pharma | Target, agonist | 0 | ||
Romiplostim | Approved | Pharma | Target, agonist, inhibitor | 0 | ||
avatrombopag | Approved, Investigational | Pharma | Target, agonist | 0 | ||
lusutrombopag | Approved, Investigational | Pharma | Target, agonist | 0 | ||
Thrombopoietin | Investigational | Pharma | Agonist, Target, agonist | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
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Compound | Action | Cas Number |
---|---|---|
Eltrombopag | 496775-61-2 | |
Eltrombopag Olamine | C-mpl agonist | 496775-62-3 |
ExUns: | 1 | ^ | 2a | · | 2b | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||
SP3: |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Cow (Bos Taurus) |
Mammalia | MPL 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Mpl 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Mpl 30 |
|
||
Dog (Canis familiaris) |
Mammalia | MPL 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MPL 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MPL 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | MPL 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | mpl 30 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
14155 | Pathogenic: Congenital amegakaryocytic thrombocytopenia | 43,349,292(+) | CT/C | FRAMESHIFT_VARIANT | |
14160 | Pathogenic: Congenital amegakaryocytic thrombocytopenia | 43,352,215(+) | G/T | SPLICE_ACCEPTOR_VARIANT | |
644406 | Pathogenic: Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia | 43,338,633(+) | C/T | MISSENSE_VARIANT | |
653595 | Likely Pathogenic: Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia | 43,338,640(+) | T/C | MISSENSE_VARIANT | |
656664 | Pathogenic: Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia | 43,348,996(+) | G/T | NONSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3585866 | CNV | loss | 21293372 |
nsv546128 | CNV | loss | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
myelofibrosis |
|
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amegakaryocytic thrombocytopenia, congenital |
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thrombocythemia 2 |
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essential thrombocythemia |
|
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myeloproliferative neoplasm |
|