Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near‐normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency

Inoue, Takafumi; Kanzaki, Akio; Kaku, Mayumi; Yawata, Ayumi; Takezono, Masami; Okamoto, Naoto; Wada, Hideho; Sugihara, Takashi; Katayama, Yasuyuki; Nagata, Noriko; Yawata, Yoshihito

doi:10.1046/j.1365-2141.1998.00868.x

Cited by 22 publications

(14 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 The effect of protein 4.2 on band-3 anion transport activity was not mimicked by coexpression of the 89-kDa band-3-binding domain of ankyrin-R with band 3, suggesting that the effect of protein 4.2 on band 3 is not a general effect of ligand binding to the N-terminal domain of band 3 but is specific to protein 4.2. Information on the binding site of protein 4.2 on the N-terminus of band 3 is limited, but natural mutations in the N-terminal domain of band 3 at Glu40, 36 Gly130, 37 and Pro327 38 lead to protein-4.2 deficiency and HS. However, these mutations do not localize to a common region of the 3-dimensional structure of the cytoplasmic domain of band 3.…”

Section: Discussionmentioning

confidence: 99%

“…This result is surprising in the context of the RBC, since the presence of band 3 is critical for the stable incorporation of protein 4.2 into the RBC membrane. 8,9,10 In addition, natural mutations that occur in the N-terminal domain of band 3, [36][37][38] which are assumed to affect the 4.2 binding site, 39 lead to protein-4.2 deficiency. This suggests that although band 3 may not be required for an initial association of 4.2 with the plasma membrane, the interaction with band 3 is required for protein-4.2 retention at the RBC plasma membrane.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Toye

Ghosh

Young

et al. 2005

Blood

View full text Add to dashboard Cite

IntroductionProtein 4.2 is a major constituent of the red blood cell (RBC) membrane skeletal network, present at about 200 000 copies per RBC. 1 The protein-4.2 gene EPB42 contains 13 exons. 2,3 There are two isoforms of protein 4.2, a minor 74-kDa isoform obtained when all these exons of the gene are expressed and a 72-kDa major isoform of protein 4.2 that lacks 30 of the 33 amino acids that are encoded by exon 1. 4,5 The exact role of protein 4.2 in RBCs has not been elucidated, but protein 4.2 binds to the N-terminal cytoplasmic domain of the band-3 anion exchanger (AE1) and also interacts with ankyrin in RBCs. 6,7 The presence of band 3 is critical for the stable incorporation of protein 4.2 into the RBC membrane, since human, 8 mouse, 9 and cow 10 RBCs deficient in band 3 are also completely deficient in protein 4.2. The functional significance of the association of protein 4.2 with band 3 in RBCs is currently unclear. In liposomes containing reconstituted band 3, anion transport activity decreased in the presence of increasing amounts of protein 4.2, 11 which suggested that protein 4.2 was a negative modulator of band-3 anion exchange activity. However, band-3-mediated anion transport activity has been reported to be unaffected 12 or increased 13 in human RBCs with protein-4.2 deficiency. In contrast, the absence of protein 4.2 slightly decreased anion transport activity in protein-4.2-null mouse RBCs. 14 Protein 4.2 also associates with spectrin, 15,16 ankyrin, 7 and protein 4.1 7 in solution, although the significance of these associations in vivo has yet to be demonstrated. Recently, protein 4.2 has been shown to interact with CD47, which probably contributes to the anchoring of the Rh complex to the RBC skeleton. 17,18 Protein 4.2 can probably interact with the inner leaflet of the lipid bilayer since it is fatty acylated with myristoyl and palmitoyl chains. 19,20 The complete or nearly complete absence of protein 4.2 is associated with an atypical form of hereditary spherocytosis (HS), highlighting the important role 4.2 plays in maintaining the stability and flexibility of RBCs. To date, 9 protein-4.2 mutations have been found associated with HS. Five lead to the premature termination of translation. 17,[21][22][23][24] Other protein-4.2 variants result from missense mutations that yield amino acid substitutions: protein 4.2 Nippon (GCTϾACT; A142T 25 ; occurs sporadically in the Japanese population and has been encountered once in whites), 26 protein 4.2 Tozeur (CGAϾCAA; R310Q), 27 protein 4.2 Shiga (CGCϾTGC; R317C), 28 and protein 4.2 Komatsu (GATϾTAT; D175Y). 29 Although there is a strict correlation between the occurrence of HS and the presence of these mutations (in homozygous or compound heterozygous states), the fact that these mutations are the direct cause of the absence of protein 4.2 has not been formally established. One possibility is that these point mutations affect the binding of protein 4.2 to band 3 and therefore its function. This has proved difficult to study using biochemical We h...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Toye

Ghosh

Young

et al. 2005

Blood

View full text Add to dashboard Cite

show abstract

“…In contrast, band 3 Fukuoka, free of bound protein 4.2, could then be normally incorporated into the lipid bilayer [60]. Thus, it has been speculated that protein 4.2 would not appear in the proband's red cell membranes [60]. Total protein 4.2 deficiency in this proband with band 3 Okinawa demonstrated marked abnormalities in biophysical properties of band 3 molecules examined by the FRAP method same as those observed in the homozygous state with the protein 4.2 gene mutations ( Figure 3).…”

Section: Total Protein 42 Deficiency In Human Band 3 Gene Mutationsmentioning

confidence: 99%

“…The decrement of the protein 4.2 content is unproportionally greater when mutations of the band 3 gene are present in its cytoplasmic domain, where the binding site(s) for protein 4.2 is located, e.g., band 3 Tuscaloosa (P327R: CCCǞCGC)[58], band 3 Montefiore (E40 K: GAGǞAAG)[59], and band 3 Fukuoka (G130R: GGAǞAGA)[60]. A homozygous state for band 3 Montefiore[59] or band 3 Fukuoka[60] showed a marked (88% or 55%, respectively) reduction of protein 4.2 content, although band 3 content was only minimally decreased, i.e., 19% or 9%, respectively.…”

mentioning

confidence: 99%

“…A homozygous state for band 3 Montefiore[59] or band 3 Fukuoka[60] showed a marked (88% or 55%, respectively) reduction of protein 4.2 content, although band 3 content was only minimally decreased, i.e., 19% or 9%, respectively. A partial (29% ± 5%) deficiency of protein 4.2[58] was discovered in red cells of hereditary spherocytosis, in which one band 3 allele was normal, but the other allele contained two mutations of the band 3 gene: (1) band 3 Memphis (K56E: AAGǞGAG) and (2) band 3 Tuscaloosa (P327R: CCCǞCGC).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells

2000

Self Cite

View full text Add to dashboard Cite

Protein 4.2 (P4.2) is one of the major red cell membrane proteins, which binds to the membrane skeletal network and to the cytoplasmic domain of anion exchanger band 3, and also interacts with ankyrin. P4.2 plays an important role in maintaining the stability and flexibility of red cells by these biophysical functions. Patients with P4.2 deficiency in their red cell membranes suffer from congenital hemolytic anemia with microspherocytosis or the like. Therefore, new information on the structure and function of the P4.2 gene, characteristics of protein 4.2, and the localization of this protein in the red cell membrane ultrastructure are reviewed. Expression of the gene and protein 4.2 in erythroid and nonerythroid tissues is discussed. In addition, the genotype and phenotype of protein 4.2 deficiency are described in humans and in the targeted P4.2 knock-out (4.2 −/− ) mice.

show abstract

The state of DNA methylation in the promoter regions of the human red cell membrane protein (band 3, protein 4.2, andβ-spectrin) genes

et al. 2001

Self Cite

View full text Add to dashboard Cite

Indrikis Muiznieks 1,5The state of methylation of the 5Ј-CpG-3Ј sites is known to be linked to the regulation of Birgit Schmitz 1 promoter function by modulating DNA-protein interactions and to the structure of chromaGudrun Schell 1 tin. As part of a project to determine methylation patterns in the human genome, the Yoshihito Yawata 2 methylation profiles were examined in genes for the human erythroid membrane proteins; Walter Doerfler 1 protein 4.2 (P4.2), gene (ELB42), band 3 (B3), gene (EPB3), and β-spectrin (β-Sp), gene 1 Institute of Genetics, University (SPTB). The bisulfite protocol of the genomic sequencing method was applied.(1) In the of Cologne, Köln, Germany DNA from peripheral white blood cells, the promoter regions of EPB3 and ELB42 were 2 Division of Hematology, extensively methylated, but the promoter of SPTB was totally unmethylated. (2) During Department of Medicine, erythroid differentiation, (i) ELB42 was unmethylated in DNAs from the cell line UT-7/EPO, Kawasaki Medical School, but became methylated (55Ϫ93%) in cultured erythroblasts from peripheral BFU-E. The Kurashiki City, Japan mRNA from ELB42 was first detected in early erythroblasts and protein 4.2 was expressed Present addresses: in late erythroblasts. (ii) EPB3 was consistently methylated in UT-7/EPO and also in cultu-3 Institute of Human Genetics red erythroblasts from burst forming unit erythroid (BFU-E) from peripheral blood. EPB3 and Anthropology, Heinrichand ELB42 were efficiently transcribed in UT-7 cells only after erythropoietin stimulation. Heine-University, Duesseldorf, (iii) SPTB remained unmethylated in DNAs from UT-7/EPO and cultured erythroblasts. (3) Germany 4 Institute of Human Genetics, We also investigated methylation profiles in peripheral white blood cells from patients with University of Essen Medical erythroid diseases, like complete P4.2 deficiency due to ELB42 mutations, hereditary School, Essen, Germany spherocytosis with EPB3 mutations, and hereditary elliptocytosis with SPTB mutations. 5 Department of Microbiology,The methylation profiles of the promoter regions of these three genes were essentially Latvian University, Riga, Latvia identical to those in healthy individuals.

show abstract

Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near‐normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency

Cited by 22 publications

References 22 publications

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells

The state of DNA methylation in the promoter regions of the human red cell membrane protein (band 3, protein 4.2, andβ-spectrin) genes

Contact Info

Product

Resources

About