Thrombopoietin receptor

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. In turn, These signaling cascades lead to the proliferation, survival, and differentiation of megakaryocytes, ultimately leading to increased platelet production.

Classification

Family (Pfam)

PF09067 EpoR_lig-bind

InterPro

FN3_dom, FN3_sf, Growth/epo_recpt_lig-bind, Ig-like_fold, Long_hematopoietin_rcpt_CS

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 1

• 8G04 EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0009986 cell surface
• GO:0009897 external side of plasma membrane
• GO:0005794 Golgi apparatus
• GO:0043025 neuronal cell body
• GO:0005886 plasma membrane
• GO:0038164 thrombopoietin receptor activity
• GO:1990960 basophil homeostasis
• GO:0071456 cellular response to hypoxia
• GO:1990959 eosinophil homeostasis
• GO:0035702 monocyte homeostasis
• GO:0001780 neutrophil homeostasis
• GO:0030220 platelet formation
• GO:0050671 positive regulation of lymphocyte proliferation
• GO:1905221 positive regulation of platelet formation
• GO:1903706 regulation of hemopoiesis
• GO:0038163 thrombopoietin-mediated signaling pathway

Disease associations

• primary myelofibrosis MONDO:0009692
• thrombocythemia 2 MONDO:0011173
• congenital amegakaryocytic thrombocytopenia 1 MONDO:0800452

Drugs targeting this protein · 6

• AVATROMBOPAG agonist
• AVATROMBOPAG MALEATE agonist
• LUSUTROMBOPAG agonist
• ELTROMBOPAG OLAMINE agonist
• RAFUTROMBOPAG agonist
• ELTROMBOPAG CHOLINE agonist

Related proteins · sequence + function similarity

• Thrombopoietin receptor 0.99
• Granulocyte colony-stimulating factor receptor 0.93
• Interleukin-11 receptor subunit alpha-2 0.91
• Interleukin-11 receptor subunit alpha-1 0.90
• Interleukin-27 receptor subunit alpha 0.90
• Interleukin-11 receptor subunit alpha 0.89
• Interleukin-11 receptor subunit alpha 0.89
• Interleukin-11 receptor subunit alpha 0.89
• Cytokine receptor common subunit gamma 0.88
• Interleukin-12 receptor subunit beta-1 0.88
• Interleukin-27 receptor subunit alpha 0.88
• Cytokine receptor common subunit beta 0.88

Co-cited proteins · studied together in the literature

• Thrombopoietin 1 shared papers
• Ataxin-2-like protein 1 shared papers
• Erythropoietin receptor 1 shared papers
• Non-receptor tyrosine-protein kinase TYK2 1 shared papers
• Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 1 shared papers
• Tyrosine-protein kinase JAK2 1 shared papers
• Tyrosine-protein kinase BTK 1 shared papers
• Tyrosine-protein kinase SYK 1 shared papers

Literature · 18 cited papers

• Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis. Cell · 2023
• Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science · 2020
• The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis. Blood · 2015
• Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling. Exp. Hematol. · 2014
• MPL W515L mutation in pediatric essential thrombocythemia. Pediatr. Blood Cancer · 2013
• Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. Blood · 2010
• The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity. Blood · 2009
• MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood · 2006
• MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. · 2006
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Hum. Mutat. · 2006
• Janus kinases affect thrombopoietin receptor cell surface localization and stability. J. Biol. Chem. · 2005
• … and 6 more in the literature graph