Disease relevance of MPP1

• Northern blot analysis indicated that p55 mRNA was constitutively expressed during erythropoiesis and underwent 2-fold amplification after induction of K562 erythroleukemia cells toward the erythropoietic lineage [1].
• Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis [2].
• Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1) [3].

High impact information on MPP1

• This study sought to develop a simple, reproducible assay, practical for screening genomic DNA samples for p55/G6PD genotypes, rapid clonality determination, and to determine the linkage relationship between these closely related loci [4].
• 209 female and 207 male genomic DNA samples were analyzed for p55/G6PD genotype by ASPCR; 60% of females were heterozygous at one or both loci [4].
• CD25 (Tac, p55), the alpha chain of the interleukin 2 receptor, is expressed on activated, but not quiescent, T cells [5].
• The abundant expression of p55 mRNA, along with protein 4.1 mRNA, was evident in terminally differentiated human reticulocytes [1].
• This fact may be partly explained by the observation that p55 is the most extensively palmitoylated protein of the erythrocyte membrane [1].

Biological context of MPP1

• We previously reported 3 X-chromosome transcription-based clonality assays (TCAs) involving the G6PD, IDS, and MPP1 genes, which together were informative in about 65% of female subjects [6].
• Normal levels of mRNA are produced from the deleted gene, with the transcripts using a cryptic polyadenylation site in the antisense strand of the adjacent MPP1 gene, normally located 1 kb downstream of DKC1 in a tail to tail orientation [7].
• The complete amino acid sequence of a 55-kDa erythrocyte membrane protein was deduced from cDNA clones isolated from a human reticulocyte library [1].
• The predicted amino acid sequence of p55 does not contain any consensus sequence corresponding to the catalytic domains of protein kinases but does contain a conserved sequence found in the noncatalytic domains of oncogene-encoded tyrosine kinases [1].
• No known factor VIII gene deletions extend into the p55 gene [8].

Anatomical context of MPP1

• Using allele-specific polymerase chain reaction (PCR) assays for the JAK2 mutation and for the X-chromosomal clonality markers IDS and MPP1, we found that the percentage of granulocytes and platelets with JAK2-V617F was often markedly lower than the percentage of clonal granulocytes determined by IDS or MPP1 clonality assays in female patients [9].
• Due to the presence of only one PDZ motif, MPP4 is part of the p55 subfamily, named after the major palmitoylated erythrocyte membrane protein p55/MPP1 [10].
• Although p55 has many features consistent with known peripheral membrane proteins, its tight association with the plasma membrane is reminiscent of an integral membrane protein [1].
• Our data provide new insights into how protein 4.1, glycophorin C, p55, and their non-erythroid homologues, interact with the cytoskeleton to exert their physiological effects [11].
• 1. We estimate that the relative utilization of the three sites in normal membranes comprises 40% to p55, 40% to GPC/D, and 20% to band 3 [12].

Associations of MPP1 with chemical compounds

• Human erythrocyte p55 is a peripheral membrane protein that contains three distinct domains in its primary structure: an N-terminal domain, an SH3 motif, and a C-terminal guanylate kinase domain [13].
• In this report we provide evidence for the direct association of p55 with the NH2-terminal 30-kDa domain of protein 4.1, a key component of the erythroid membrane skeleton [14].
• In this investigation, synthetically tagged peptides and bacterially expressed proteins were used to map the protein 4.1 binding site on human erythroid glycophorin C, a transmembrane glycoprotein, and on human erythroid p55, a palmitoylated peripheral membrane phosphoprotein [11].

Physical interactions of MPP1

• PIP(2) had no effect on 4.1R binding to p55 [15].
• In addition, p55 also binds to the cytoplasmic domain of glycophorin C, a transmembrane protein of red blood cells [14].

Other interactions of MPP1

• As MPP1 and CRYAB are also among the 14 genes differentially expressed in all three of the drug-resistant sublines, they represent the strongest candidates for resistance against DNA-damaging drugs [16].
• On a stoichiometric basis, the reduction in glycophorin C (about 80%) was concomitant to the lack of p55 in RBCs devoid of protein 4 [13].
• 4.1R promotes the formation of a ternary complex with GPC and p55 through its 30 kDa membrane-binding domain [17].
• This protein, p55, is copurified during the isolation of dematin, an actin-bundling protein of the erythrocyte membrane cytoskeleton [1].
• Finally, promoter activity measurements of the region immediately upstream of the p55 gene, which contains several cis-elements commonly found in housekeeping genes, suggest that a CpG island may be associated with the p55 gene expression in vivo [18].

Analytical, diagnostic and therapeutic context of MPP1

• RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene [2].

References