Recombinant Human Thrombopoietin receptor (MPL), partial

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

Subcellular Location

Cell membrane (Single-pass type I membrane protein); Golgi apparatus; Cell surface

Disease Association

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. [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. [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. [The disease is caused by variants affecting the gene represented in this entry]

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

Subunit

Homodimer (PubMed:32029621, PubMed:25538044). Interacts with ATXN2L (PubMed:11784712). Interacts with JAK2 and TYK2; these interactions increase MPL localization to the cell membrane (PubMed:15899890). Interacts with THPO (PubMed:37633268). Interacts with SHIP/INPP5D (PubMed:24607955). Interacts with BTK (PubMed:24607955). Interacts with SYK; this interaction negatively regulates THPO-mediated ERK1/2 signaling (PubMed:24607955)

• Vigon I. et al. Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily. — Proc. Natl. Acad. Sci. U.S.A. (1992)
• Mignotte V. et al. Structure and transcription of the human c-mpl gene (MPL). — Genomics (1994)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• Royer Y. et al. Janus kinases affect thrombopoietin receptor cell surface localization and stability. — J. Biol. Chem. (2005)
• Saur S.J. et al. Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. — Blood (2010)
• Sangkhae V. et al. Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling. — Exp. Hematol. (2014)
• Cargill M. et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. — Nat. Genet. (1999)