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Missense mutations in the C-terminal portion of the B4GALNT2-encoded glycosyltransferase underlying the Sd(a−) phenotype

Stenfelt, Linn, Hellberg, Åsa, Möller, Mattias, Thornton, Nicole, Larson, Göran, Olsson, Martin L.·2019·Biochemistry and Biophysics Reports
DOI 10.1016/j.bbrep.2019.100659PMC PMC6646742
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Fig. 1 The rs7224888 and additional SNPs that correlates with Sd(a−) phenotype. (A) Human B4GALNT2 on chromosome 17 encodes three transcripts, differing in sequence due to differential use of exon 1; long (red box), short (blue box) or, a so far only theoretical, middle length exon 1 (green box) as stated in Ensembl release 96 [39]. All transcripts use the same coding sequence of exons 2–11 (black boxes), while the UTR of exon 11 differs (colored accordingly). Black horizontal lines in between the exons depict the introns. (B) The SNPs identified in nine individuals with the Sd(a−) phenotype, after sequencing the coding regions and the proposed promoter of the gene. Magnified sequences surrounding the SNPs (underlined) are shown at the stated nucleotide positions and below follows the SNP status of each subject symbolized by stick figures. The variants of interest are written in white. For one of the rs7224888 homozygotes, nucleotide status for rs148441237 was not established. (C) Schematic sketch of the translated proteins from each transcript. Depending on which exon 1 is utilized the product is predicted to encode a transmembrane (NP_703147 and NP_001152859) or a soluble (NP_001152860) glycosyltransferase. The amino acid changes caused by the identified SNPs are found C-terminally of the DXD motif (in this case three consecutive aspartic acids, DDD) and are described in the dark grey boxes on the right and the amino acid positions are stated for each isoform.
Fig. 1 The rs7224888 and additional SNPs that correlates with Sd(a−) phenotype. (A) Human B4GALNT2 on chromosome 17 encodes three transcripts, differing in sequence due to differential use of exon 1; long (red box), short (blue box) or, a so far only theoretical, middle length exon 1 (green box) as stated in Ensembl release 96 [39]. All transcripts use the same coding sequence of exons 2–11 (black boxes), while the UTR of exon 11 differs (colored accordingly). Black horizontal lines in between the exons depict the introns. (B) The SNPs identified in nine individuals with the Sd(a−) phenotype, after sequencing the coding regions and the proposed promoter of the gene. Magnified sequences surrounding the SNPs (underlined) are shown at the stated nucleotide positions and below follows the SNP status of each subject symbolized by stick figures. The variants of interest are written in white. For one of the rs7224888 homozygotes, nucleotide status for rs148441237 was not established. (C) Schematic sketch of the translated proteins from each transcript. Depending on which exon 1 is utilized the product is predicted to encode a transmembrane (NP_703147 and NP_001152859) or a soluble (NP_001152860) glycosyltransferase. The amino acid changes caused by the identified SNPs are found C-terminally of the DXD motif (in this case three consecutive aspartic acids, DDD) and are described in the dark grey boxes on the right and the amino acid positions are stated for each isoform.CC BY-NC-ND · PubMed Central
Fig. 2 The 3D protein structure of β-1,4-N-acetylgalactosaminyltransferase 2, based on homology modelling of the crystal structure of chondroitin synthase from E. coli, using SWISS-MODEL [32]. (A) The model consists of amino acids 319–524 in the catalytic domain and is colored by residue number from red in the N-terminal via yellow to blue in the C-terminal. The protein is predicted to form a dimer, as is common for glycosyltransferases. (B) A close-up view of the structure detailing the locations of the DXD motif and the three SNPs of interest in relation to the Sd(a−) phenotype.
Fig. 2 The 3D protein structure of β-1,4-N-acetylgalactosaminyltransferase 2, based on homology modelling of the crystal structure of chondroitin synthase from E. coli, using SWISS-MODEL [32]. (A) The model consists of amino acids 319–524 in the catalytic domain and is colored by residue number from red in the N-terminal via yellow to blue in the C-terminal. The protein is predicted to form a dimer, as is common for glycosyltransferases. (B) A close-up view of the structure detailing the locations of the DXD motif and the three SNPs of interest in relation to the Sd(a−) phenotype.CC BY-NC-ND · PubMed Central
Fig. 3 The rs7224888 is located in a highly conserved region among different species. Homologous proteins with significant amino acid alignments based on Protein BLAST of amino acids 451–481. Sequence identity represents similarity with human β-1,4-N-acetylgalactosaminyltransferase 2 (top row) in the analyzed region. Start refers to the position of the first amino acid shown on each line. The red frame shows the amino acid altered by rs7224888 (p.Cys466Arg), and the corresponding amino acids in the related proteins. Light blue, middle blue, and dark blue boxes symbolize identity between 9 and 10, 11–12, or all 13 of the compared sequences, respectively. The figure shows that a highly homologous region can be found in β-1,4-N-acetylgalactosaminyltransferase 1 in many species, and that the cysteine at position 466, as well as many surrounding residues, is conserved in all proteins.
Fig. 3 The rs7224888 is located in a highly conserved region among different species. Homologous proteins with significant amino acid alignments based on Protein BLAST of amino acids 451–481. Sequence identity represents similarity with human β-1,4-N-acetylgalactosaminyltransferase 2 (top row) in the analyzed region. Start refers to the position of the first amino acid shown on each line. The red frame shows the amino acid altered by rs7224888 (p.Cys466Arg), and the corresponding amino acids in the related proteins. Light blue, middle blue, and dark blue boxes symbolize identity between 9 and 10, 11–12, or all 13 of the compared sequences, respectively. The figure shows that a highly homologous region can be found in β-1,4-N-acetylgalactosaminyltransferase 1 in many species, and that the cysteine at position 466, as well as many surrounding residues, is conserved in all proteins.CC BY-NC-ND · PubMed Central
Fig. 4 The rs7224888 resides in a haplotype block of ~32 kb (A) Linkage disequilibrium (LD) between rs7224888 and other variants in B4GALNT2 and neighboring genes. Each dot represents a variant detected in the 1000 Genomes Project [23] and is color-coded according to its location. The long transcript (ENST00000300404) was used for color-coding variants in B4GALNT2. Variants in AC069454.1 were coded as intronic. The x-axis shows the chromosomal location according to the GRCh37/hg19 human reference genome and the y-axis shows the level of LD with rs7224888 (R2). (B) The B4GALNT2 transcripts and the canonical transcripts for neighboring genes ABI3, GNGT2 and PHOSPO1. AC069454.1 is a ribosomal protein S10 (RPS10) pseudogene and RP11-708H21.4 is long non-coding RNA (lncRNA). The orange shaded area represents a presumed haplotype of ~32 kb, where 66 variants exhibit strong LD (R2 > 0.6) with rs7224888. This haplotype consists of exon 10 and 11 in all B4GALNT2 transcripts as well as RP11-708H21.4. The two other exonic variants in this haplotype are synonymous (rs16946912) or located in the 3′ UTR (rs28689968).
Fig. 4 The rs7224888 resides in a haplotype block of ~32 kb (A) Linkage disequilibrium (LD) between rs7224888 and other variants in B4GALNT2 and neighboring genes. Each dot represents a variant detected in the 1000 Genomes Project [23] and is color-coded according to its location. The long transcript (ENST00000300404) was used for color-coding variants in B4GALNT2. Variants in AC069454.1 were coded as intronic. The x-axis shows the chromosomal location according to the GRCh37/hg19 human reference genome and the y-axis shows the level of LD with rs7224888 (R2). (B) The B4GALNT2 transcripts and the canonical transcripts for neighboring genes ABI3, GNGT2 and PHOSPO1. AC069454.1 is a ribosomal protein S10 (RPS10) pseudogene and RP11-708H21.4 is long non-coding RNA (lncRNA). The orange shaded area represents a presumed haplotype of ~32 kb, where 66 variants exhibit strong LD (R2 > 0.6) with rs7224888. This haplotype consists of exon 10 and 11 in all B4GALNT2 transcripts as well as RP11-708H21.4. The two other exonic variants in this haplotype are synonymous (rs16946912) or located in the 3′ UTR (rs28689968).CC BY-NC-ND · PubMed Central

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Cites

  • Ensembl 2019

    Cunningham, F., Achuthan, P., Akanni, W., Allen, J., Amode, M. R., Armean, I. M., Bennett, R., Bhai, J., Billis, K., Boddu, S., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1113 · Cited by 925

Research works printed but not linked: 40

  1. Renton, 1967, Anti-Sda, a new blood group antibody, Vox Sang., 13, 493
  2. Macvie, 1967, The reactions and inheritance of a new blood group antigen, Sda, Vox Sang., 13, 485
  3. Morton, 1970, The Sda blood group antigen in tissues and body fluids, Vox Sang., 19, 472
  4. Blanchard, 1985, Comparative study of glycophorin A derived O-glycans from human Cad, Sd(a+) and Sd(a-) erythrocytes, Biochem. J., 232, 813, 10.1042/bj2320813 · DOI
  5. Donald, 1983, A blood group Sda-active pentasaccharide isolated from Tamm-Horsfall urinary glycoprotein, Biochem. Biophys. Res. Commun., 115, 625, 10.1016/S0006-291X(83)80190-9 · DOI
  6. Dohi, 1996, Detection of N-acetylgalactosaminyltransferase mRNA which determines expression of Sda blood group carbohydrate structure in human gastrointestinal mucosa and cancer, Int. J. Cancer, 67, 626, 10.1002/(SICI)1097-0215(19960904)67:5<626::AID-IJC6>3.0.CO;2-W · DOI
  7. Lo Presti, 2003, Molecular cloning of the human β1,4 N-acetylgalactosaminyltransferase responsible for the biosynthesis of the Sda histo-blood group antigen: the sequence predicts a very long cytoplasmic domain, J. Biochem., 134, 675, 10.1093/jb/mvg192 · DOI
  8. Montiel, 2003, Molecular cloning, gene organization and expression of the human UDP-GalNAc:Neu5Acα2-3Galβ-R β1,4-N-acetylgalactosaminyltransferase responsible for the biosynthesis of the blood group Sda/Cad antigen: evidence for an unusual extended cytoplasmic domain, Biochem. J., 373, 369, 10.1042/bj20021892 · DOI · Paper page
  9. Jöud, 2018, Identification of human glycosyltransferase genes expressed in erythroid cells predicts potential carbohydrate blood group loci, Sci. Rep., 8, 6040, 10.1038/s41598-018-24445-5 · DOI
  10. Takeya, 1987, Identification and characterization of UDP-GalNAc: NeuAcα2−3Galβ1−4Glc(NAc) β1−4(GalNAc to Gal)N-acetylgalactosaminyltransferase in human blood plasma, J. Biochem., 101, 251, 10.1093/oxfordjournals.jbchem.a121898 · DOI
  11. Spitalnik, 1982, The serology of Sda effects of transfusion and pregnancy, Vox Sang., 42, 308
  12. Malagolini, 1989, Expression of UDP-GalNAc:NeuAcα2,3Galβ-R β1,4(GalNAc to Gal)N-acetylgalactosaminyltransferase involved in the synthesis of Sda antigen in human large intestine and colorectal carcinomas, Cancer Res., 49, 6466
  13. Serafini-Cessi, 2005, N-Glycans carried by Tamm-Horsfall glycoprotein have a crucial role in the defense against urinary tract diseases, Glycoconj. J., 22, 383, 10.1007/s10719-005-2142-z · DOI
  14. Cartron, 1983, Susceptibility to invasion by Plasmodium falciparum of some human erythrocytes carrying rare blood group antigens, Br. J. Haematol., 55, 639, 10.1111/j.1365-2141.1983.tb02846.x · DOI
  15. Heaton, 2017, A CRISPR activation screen identifies a pan-avian influenza virus inhibitory host factor, Cell Rep., 20, 1503, 10.1016/j.celrep.2017.07.060 · DOI
  16. Tanaka-Okamoto, 2018, Identification of internally sialylated carbohydrate tumor marker candidates, including Sda/CAD antigens, by focused glycomic analyses utilizing the substrate specificity of neuraminidase, Glycobiology, 28, 247, 10.1093/glycob/cwy010 · DOI
  17. Guo, 2018, Molecular cloning of the B4GALNT2 gene and its single nucleotide polymorphisms association with litter size in small tail han sheep, Animals, 8, 160, 10.3390/ani8100160 · DOI
  18. Byrne, 2018, B4GALNT2 and xenotransplantation: a newly appreciated xenogeneic antigen, Xenotransplantation, 25, 10.1111/xen.12394 · DOI
  19. Dall’Olio, 2014, The expanding roles of the Sda/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2, Biochim. Biophys. Acta, 1840, 443, 10.1016/j.bbagen.2013.09.036 · DOI
  20. Miller, 1988, A simple salting out procedure for extracting DNA from human nucleated cells, Nucleic Acids Res., 16, 1215, 10.1093/nar/16.3.1215 · DOI
  21. Hellberg, 2003, Additional molecular bases of the clinically important p blood group phenotype, Transfusion, 43, 899, 10.1046/j.1537-2995.2003.00425.x · DOI
  22. The 1000 Genomes Project Consortium, 2015, A global reference for human genetic variation, Nature, 526, 68, 10.1038/nature15393 · DOI · Paper page
  23. Möller, 2016, Erythrogene: a database for in-depth analysis of the extensive variation in 36 blood group systems in the 1000 Genomes Project, Blood Adv, 1, 240, 10.1182/bloodadvances.2016001867 · DOI
  24. Sudmant, 2015, An integrated map of structural variation in 2,504 human genomes, Nature, 526, 75, 10.1038/nature15394 · DOI · Paper page
  25. Adzhubei, 2010, A method and server for predicting damaging missense mutations, Nat. Methods, 7, 248, 10.1038/nmeth0410-248 · DOI · Paper page
  26. Vaser, 2016, SIFT missense predictions for genomes, Nat. Protoc., 11, 1, 10.1038/nprot.2015.123 · DOI · Paper page
  27. Zerbino, 2018, Ensembl 2018, Nucleic Acids Res., 46, D754, 10.1093/nar/gkx1098 · DOI · Paper page
  28. Lek, 2016, Analysis of protein-coding genetic variation in 60,706 humans, Nature, 536, 285, 10.1038/nature19057 · DOI · Paper page
  29. Ameur, 2017, SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population, Eur. J. Hum. Genet., 25, 1253, 10.1038/ejhg.2017.130 · DOI
  30. Berman, 2000, The Protein Data Bank, Nucleic Acids Res., 28, 235, 10.1093/nar/28.1.235 · DOI · Paper page
  31. Waterhouse, 2018, SWISS-MODEL: homology modelling of protein structures and complexes, Nucleic Acids Res., 46, W296, 10.1093/nar/gky427 · DOI
  32. Osawa, 2009, Crystal structure of chondroitin polymerase from Escherichia coli K4, Biochem. Biophys. Res. Commun., 378, 10, 10.1016/j.bbrc.2008.08.121 · DOI
  33. Rose, 2018, NGL viewer: web-based molecular graphics for large complexes, Bioinformatics, 34, 3755, 10.1093/bioinformatics/bty419 · DOI · Paper page
  34. Altschul, 1990, Basic local alignment search tool, J. Mol. Biol., 215, 403, 10.1016/S0022-2836(05)80360-2 · DOI · Paper page
  35. Machiela, 2015, LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants, Bioinformatics, 31, 3555, 10.1093/bioinformatics/btv402 · DOI · Paper page
  36. Desmet, 2009, Human Splicing Finder: an online bioinformatics tool to predict splicing signals, Nucleic Acids Res., 37, e67, 10.1093/nar/gkp215 · DOI
  37. Barretina, 2012, The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity, Nature, 483, 603, 10.1038/nature11003 · DOI · Paper page
  38. Breton, 2006, Structures and mechanisms of glycosyltransferases, Glycobiology, 16, 29r, 10.1093/glycob/cwj016 · DOI
  39. Sringarm, 1974, Cad receptor in Thai blood donors, Vox Sang., 26, 462, 10.1111/j.1423-0410.1974.tb02721.x · DOI
  40. Sun, 2017, Down-regulation of long non-coding RNA RP11-708H21.4 is associated with poor prognosis for colorectal cancer and promotes tumorigenesis through regulating AKT/mTOR pathway, Oncotarget, 8, 27929, 10.18632/oncotarget.15846 · DOI

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Metadata

Authors
Stenfelt, L., Hellberg, Å., Möller, M., Thornton, N., Larson, G., & Olsson, M. L.
Venue
Biochemistry and Biophysics Reports
Publisher
Elsevier BV
Published
2019-09
Volume
19
Pages
100659
ISSN
2405-5808
DOI
10.1016/j.bbrep.2019.100659
PMC
PMC6646742
Cited by
15
References
1
Language
en
Licence
Funders
  • Vetenskapsrådet
  • Knut och Alice Wallenbergs Stiftelse

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