MPL
Domain
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
Function
Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. Upon activation by THPO, induces rapid tyrosine phosphorylation and activation of JAK2, providing docking sites for many signaling proteins such as STAT5, SHIP/INPP5D, GRB2, SOS1 and PI3K (PubMed:15899890, PubMed:37633268). In turn, These signaling cascades lead to the proliferation, survival, and differentiation of megakaryocytes, ultimately leading to increased platelet production.
Involvement in disease
Amegakaryocytic thrombocytopenia, congenital, 1
CAMT1
An autosomal recessive form of congenital amegakaryocytic thrombocytopenia, a hematologic disorder characterized by severe reduction of megakaryocytes and platelets at birth, and evolving into generalized bone marrow aplasia during childhood.
None
The disease is caused by variants affecting the gene represented in this entry.
Thrombocythemia 2
THCYT2
A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
None
The disease is caused by variants affecting the gene represented in this entry.
Myelofibrosis with myeloid metaplasia
MMM
A chronic myeloproliferative disorder characterized by replacement of the bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia, leukoerythroblastosis and hepatosplenomegaly.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated at Tyr-591 in response to THPO stimulation.
Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.
Sequence Similarities
Belongs to the type I cytokine receptor family. Type 1 subfamily.
Tissue Specificity
Expressed at a low level in a large number of cells of hematopoietic origin. Isoform 1 and isoform 2 are always found to be coexpressed.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Golgi apparatus
- Cell surface
Alternative names
CD110, TPOR, MPL, Thrombopoietin receptor, TPO-R, Myeloproliferative leukemia protein, Proto-oncogene c-Mpl