Abstract
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. Mutations to this gene are associated with myelofibrosis and essential Thrombocythemia. In essential Thrombocythemia, these mutations lead to the production of Thrombopoietin receptors that are constitutively activated, or constantly turned on, which results in the overproduction of abnormal megakaryocytes. MPL gene was investigated in NCBI database (http://www.ncbi.nlm.nih.gov/) and computational software’s analyzed SNPs. SNPs in the coding region (exonal SNPs) that are non-synonymous (nsSNP) were analyzed by (sift, polyphen, Imutant and PHD-snp) softwares, and then SNPs at un-traslated region at 5’ ends (5UTR) were analyzed too by SNPs Function prediction software. In this study, Bioinformatics’ analysis of MPL gene initiated by SIFTand Polyphen-2server issued to review 197 SNPs and among this SNPs 23 pathological polymorphisms. Among these 23, 20 pathological polymorphisms were found to be very damaging, with higher Polyphen-2score, of the Polyphen-2 server (=1) and SIFT tolerance index of 0.000-0.005. Protein structural analysis was done by modeling of amino acid substitutions using Project Hope. AlsoI-Mutant software used to check their stability and the effect of the native and mutant residues protein and structure for all these pathological polymorphisms. We hope our results will provide useful information that is needed to help researchers to do further studies.
Highlights
MPL is a protein in human encoded by or CD110, known as a Thrombopoietin receptor. [1] The Oncogene was identified in 1990 from the murine myeloproliferative leukemia virus and has the capability of immortalizing bone marrow hematopoietic cells from different lineages
For Polyphen-2 there where, 20 nsSNPs predicted as damaging while three were benign, the damaging Single Nucleotide Polymorphisms (SNPs) has impact on amino acid allelic variants, protein structure and function
The present study found that 16 SNPs were scored to decrease the stability of the protein, While only seven SNPs had increased in the stability of the protein
Summary
MPL is a protein in human encoded by (myeloproliferative leukemia protein) or CD110, known as a Thrombopoietin receptor. [1] The Oncogene was identified in 1990 from the murine myeloproliferative leukemia virus and has the capability of immortalizing bone marrow hematopoietic cells from different lineages. MPL is a protein in human encoded by (myeloproliferative leukemia protein) or CD110, known as a Thrombopoietin receptor. [1] The Oncogene was identified in 1990 from the murine myeloproliferative leukemia virus and has the capability of immortalizing bone marrow hematopoietic cells from different lineages. In 1992, the human homologue, named, c-mpl, was cloned. 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. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presences of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and Thrombopoietin in megakaryocyte and platelet formation.
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