Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human protein 4.2 (P4.2) is a major membrane skeletal protein in erythrocytes. Individuals with P4.2 deficiency exhibit spherocytosis and experience various degrees of hemolytic anemia, suggesting a role for this protein in maintaining stability and integrity of the membrane. Molecular cloning of P4.2 cDNAs showed that P4.2 is a transglutaminaselike molecule in erythrocytes but lacks the essential cysteine for cross-linking activity. Two cDNA isoforms have been identified from a human reticulocyte cDNA library, with the long isoform containing a 90-base pair (bp) in-frame insertion encoding an extra 30 amino acids near the N-terminus. Characterization of the P4.2 gene suggests differential splicing as the mechanism for generating these two cDNA isoforms. The donor site for the short isoform (P4.2S) agrees better with the consensus than the donor site for the long isoform (P4.2L) does. Expression of P4.2L was detected by a long-isoform-specific antibody raised against a peptide within the 30-amino acid insert. Western blot analyses showed P4.2L to be a minor membrane skeletal protein in human erythrocytes with an apparent molecular weight (mol wt) of approximately 3 Kd larger than the major protein 4.2, P4.2S. By in situ hybridization of a full-length 2.4-kilobase (kb) cDNA to human metaphase chromosomes, the gene for P4.2 was mapped to bands q15-q21 of chromosome 15, and it is not linked to the gene for coagulation factor XIIIa (plasma transglutaminase, TGase).
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PMID:Human erythrocyte protein 4.2: isoform expression, differential splicing, and chromosomal assignment. 135 Feb 27

Erythrocyte (RBC) protein 4.2 (P4.2)-deficiency observed in Japanese individuals results in a hemolytic anemia associated with abnormally shaped (spherocytic, ovalocytic, and elliptocytic), osmotically fragile RBCs, the clinical presentation of which resembles hereditary spherocytosis (HS). By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, P4.2-deficient individuals contain less than 1% of the normal membrane content of P4.2 and immunologic analysis shows that the P4.2 present exists as an equimolar doublet of 74-Kd and 72-Kd bands, in contrast to normal RBC membranes where a discrete 74-Kd band is not observed. RBC membranes from both of the biologic parents of a P4.2-deficient individual contained both the 74-Kd and the 72-Kd bands, demonstrating their heterozygosity for the P4.2 defect. The molecular basis of Japanese P4.2-deficiency was investigated by reverse transcription of total reticulocyte RNA, followed by polymerase chain reaction (PCR) amplification, subcloning, and sequencing. The complete cDNA sequence of a P4.2-deficient patient showed a single point mutation that changes codon 142 from GCT (alanine) to ACT (threonine) (Protein 4.2NIPPON). The mutation also eliminated an HgaI restriction site, therefore allowing rapid screening for the presence of the mutation. Screening of PCR-amplified genomic DNA showed that the mutation was present in the homozygous state in four (eight chromosomes) unrelated Japanese P4.2-deficient individuals and absent in 35 (70 chromosomes) P4.2-normal controls (including 15 Japanese [30 chromosomes]). The presence of the mutation was confirmed by allele-specific hybridization. The mutation occurred in an alternatively spliced exon that is present in two of four P4.2 mRNA splicing isoforms. These results demonstrate that Japanese P4.2-deficiency is closely associated with the P4.2 gene and does not arise secondarily to a defect in another membrane protein, and further suggest that the P4.2-deficiency is related to the pathogenesis of the hemolytic anemia in this variant form of recessively inherited spherocytosis.
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PMID:An alanine-to-threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia (protein 4.2NIPPON). 155 76

Protein 4.2 (P4.2), one of the major components of the red-blood-cell membrane, is located on the interior surface, where it binds with high affinity to the cytoplasmic domain of band 3. Individuals whose red blood cells are deficient in P4.2 have osmotically fragile, abnormally shaped cells and moderate hemolytic anemia. cDNA clones from both the 5' and the 3' coding regions of the P4.2 gene were used to map its chromosomal location by fluorescence in situ hybridization. The probes, individually or in combination, gave specific hybridization signals on chromosome 15. The hybridization locus was identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by Alu-PCR (R-like) probe and by DAPI staining (G-like). Our results demonstrate that the locus of the P4.2 gene is located within 15q15.
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PMID:The gene for human erythrocyte protein 4.2 maps to chromosome 15q15. 172 96

The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.
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PMID: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. 973 43