Kell, Kx and the McLeod syndrome

Redman, Colvin M.; Russo, David; Lee, Soohee

doi:10.1053/beha.1999.0045

Cited by 43 publications

(30 citation statements)

References 85 publications

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“…These data underscore the added power of studying full-length proteins in their native environment. Moreover, a number of protein interactions in the red cell membrane have been described, such as Rh50-LW 41 and Kell-KX, 42 in which one binding partner has multiple transmembrane spans and the other has a single span. We speculate that the association between band 3 and GPA may serve as a model for interactions of other multipass and single-pass polypeptides during membrane biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice

Auffray

Marfatia

Jong

et al. 2001

Blood

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Band 3 and glycophorin A (GPA) are the 2 most abundant integral proteins in the human erythrocyte membrane. Earlier studies suggested that the 2 proteins may associate not only in the mature erythrocyte membrane, but also during their posttranslational processing and intracellular trafficking. The purpose of this study was to directly examine the GPA-band 3 interaction in vivo and determine the nature of this association during erythroid membrane biogenesis. Transgenic mice were generated expressing the human glycophorin A gene and were used to examine how the induction of human GPA expression affected the levels of murine GPA and band 3 expression in the red cell membrane. Murine GPA expression was reduced in erythrocytes expressing human GPA, whereas the level of band 3 expression remained constant, implying a tight coupling of band 3 and GPA expression in the membrane of mature red cells. In vivo GPA dimerization was not modulated solely by the GPA transmembrane motif, but the distance between this motif and the basic residues on the cytoplasmic side of the transmembrane domain may also be important. In addition, GPA monomers with vary- IntroductionThe 2 most abundant integral proteins in the human erythrocyte membrane are the sialoglycoprotein glycophorin A (GPA) and the anion exchanger band 3. GPA, present at 800 000 copies per cell, is a class I transmembrane protein assembled into dimers in the mature erythrocyte membrane. [1][2][3] Human GPA undergoes homodimerization by associations between hydrophobic membranespanning domains. 4,5 With its high sialic acid content, GPA is the main contributor to the net negative cell-surface charge and is thus critical for minimizing cell-cell interactions and preventing red cell aggregation. In contrast, erythrocyte band 3 is a multifunctional protein with its N-and C-terminal domains on the cytoplasmic face of the lipid bilayer and approximately 14 membrane spans. [6][7][8] The C-terminal 52-kd membrane domain (residues 360-919) of band 3 is responsible for anion transport across the membrane, whereas the 40-kd N-terminal cytoplasmic domain plays a crucial structural role in linking the bilayer with the spectrin-based skeletal network. There are 1 ϫ 10 6 copies of band 3 per cell, which are present as a mixture of dimers and tetramers. Approximately 40% to 60% of band 3 appears to be associated with the spectrin-based skeleton.Although evidence to support a direct interaction between GPA and band 3 has remained equivocal, intriguing data suggest that the 2 proteins may associate not only in the mature erythrocyte membrane, but also during their posttranslational processing and/or intracellular trafficking during erythropoiesis. Evidence supporting an interaction in the plasma membrane includes the finding that binding of antibody to the extracellular domain of GPA decreases both the rotation 9 and lateral mobility 10 of band 3. In addition, the expression of blood group antigen Wr b requires the surface expression of both GPA and band 3 11,12 and appears to involve ...

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Section: Discussionmentioning

confidence: 99%

Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice

Auffray

Marfatia

Jong

et al. 2001

Blood

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“…The physiological functions of Kell and XK have not been fully elucidated, but Kell is a zinc endopeptidase with endothelin-3-converting enzyme activity and XK has the structural characteristics of a membrane transporter (Redman et al, 1999;Sha et al, 2006).…”

Section: M13 Familymentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

210

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…Ko red cells have a reduced amount of XK protein (9), but, parenthetically, they have enhanced Kx antigen activity (1,2,10). Kell is a zinc endopeptidase and a member of the M13 or neprilysin family whose principal functions are the activation of bioactive peptides by proteolytic cleavage of larger inactive polypeptides (11).…”

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confidence: 99%

Molecular Defects Underlying the Kell Null Phenotype

Lee¹,

Russo²,

Reiner³

et al. 2001

Journal of Biological Chemistry

Self Cite

121

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Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5 splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5 splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.

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Kell, Kx and the McLeod syndrome

Cited by 43 publications

References 85 publications

Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice

Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Molecular Defects Underlying the Kell Null Phenotype

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