Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Band 3 is the predominant polypeptide and the purported mediator of anion transport in the human erythrocyte membrane. Against a background of minor and apparently unrelated polypeptides of similar electrophoretic mobility, and despite apparent heterogeneity in its glycosylation, the bulk of band 3 exhibits uniform and characteristic behavior. This integral glycoprotein appears to exist as a noncovalent dimer of two approximately 93,000-dalton chains which span the membrane asymmetrically. The protein is hydrophobic in its composition and in its behavior in aqueous solution and is best solubilized and purified in detergent. It can be cleaved while membrane-bound into large, topographically defined segments. An integral, outer-surface, 38,000-dalton fragment bears most of the band 3 carbohydrate. A 17,000-dalton, hydrophobic glycopeptide fragment spans the membrane. A approximately 40,000-dalton hydrophilic segment represents the cytoplasmic domain. In vitro, glyceraldehyde 3-P dehydrogenase and aldolase bind reversibly, in a metabolie-sensitive fashion, to this cytoplasmic segment. The cytoplasmic domain also bears the amino terminus of this polypeptide, in contrast to other integral membrane proteins. Recent electron microscopic analysis suggests that the poles of the band 3 molecule can be seen by freeze-etching at the two original membrane surfaces, while freeze-fracture reveals the transmembrane disposition of band 3 dimer particles. There is strong evidence that band 3 mediates 1:1 anion exchange across the membrane through a conformational cycle while remaining fixed and asymmetrical. Its cytoplasmic pole can be variously perturbed and even excised without a significant alteration of transport function. However, digestion of the outer-surface region leads to inhibition of transport, so that both this segment and the membrane-spanning piece (which is selectively labeled by covalent inhibitors of transport) may be presumed to be involved in transport. Genetic polymorphism has been observed in the structure and immunogenicity of the band 3 polypeptide but this feature has not been related to variation in anion transport or other band 3 activities.
 ...
PMID:The band 3 protein of the human red cell membrane: a review. 36 94

A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti-dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution.
 ...
PMID:[A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers]. 218 62

Two brothers, 25 and 19 years old, were affected by asymmetrical hypertrophic cardiomyopathy. The older brother had waddling gait and weakness of the proximal girdle muscles, while the younger had a broad-based gait and weakness of selected limb girdle muscles. EMG exam was myopathic. Serum enzyme, CPK and aldolase were elevated. Histochemical reactions in muscle revealed "core-like" areas, subsarcolemmal rims of mitochondria and lipid accumulation. Succinate-dehydrogenase stain showed a lack of activity in both biopsies, with the exception of intrafusal fibers. Microphotometric quantitative measurements confirmed the defect in both biopsies. Biochemical measurements of several mitochondrial enzymes in muscle showed a reduced activity of succinate-dehydrogenase (33%) and succinate-cytochrome C reductase (36-47%) which are both components of complex II. On myocardial biopsy lipid and mitochondrial abnormalities were found. This mitochondriopathy represents a new phenotype of partial complex II defect.
 ...
PMID:Hypertrophic cardiomyopathy with mitochondrial myopathy. A new phenotype of complex II defect. 851 73

A 68 nucleotide segment of the light neurofilament (NF-L) mRNA, spanning the translation termination signal, participates in regulating the stability of the transcript in vivo. Aldolases A and C, but not B, interact specifically with this segment of the transcript in vitro. Aldolases A and C are glycolytic enzymes expressed in neural cells, and their mRNA binding activity represents a novel function of these isozymes. This unsuspected new activity was first uncovered by Northwestern blotting of a brainstem/spinal cord cDNA library. It was confirmed by two-dimensional fractionation of mouse brain cytosol followed by Northwestern hybridization and protein sequencing. Both neuronal aldolases interact specifically with the NF-L but not the heavy neurofilament mRNA, and their binding to the transcript excludes the poly(A)-binding protein (PABP) from the complex. Constitutive ectopic expression of aldolases A and C accelerates the decay of a neurofilament transgene (NF-L) driven by a tetracycline inducible system. In contrast, mutant transgenes lacking mRNA sequence for aldolase binding are stabilized. Our findings strongly suggest that aldolases A and C are regulatory components of a light neurofilament mRNA complex that modulates the stability of NF-L mRNA. This modulation likely involves endonucleolytic cleavage and a competing interaction with the PABP. Interactions of aldolases A and C in NF-L expression may be linked to regulatory pathways that maintain the highly asymmetrical form and function of large neurons.
 ...
PMID:Aldolases a and C are ribonucleolytic components of a neuronal complex that regulates the stability of the light-neurofilament mRNA. 1585 61