CD77 synthase

Summary

Gene Symbol: CD77 synthase
Description: alpha 1,4-galactosyltransferase (P blood group)
Alias: A14GALT, A4GALT1, Gb3S, P1PK, lactosylceramide 4-alpha-galactosyltransferase, CD77 synthase, GB3 synthase, P blood group (P one antigen), P one antigen (P blood group), P(k) antigen synthase, P1/Pk synthase, UDP-galactose:beta-D-galactosyl-beta1-R 4-alpha-D-galactosyltransferase, alpha 14-galactosyltransferase, alpha-1,4-N-acetylglucosaminyltransferase, alpha-1,4-galactosyltransferase, alpha4Gal-T1, globotriaosylceramide synthase, truncated alpha 1,4-galactosyltransferase
Species: human
Products:     CD77 synthase

Top Publications

  1. Steffensen R, Carlier K, Wiels J, Levery S, Stroud M, Cedergren B, et al. Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype. J Biol Chem. 2000;275:16723-9 pubmed
    ..Sequence analysis of the coding region of alpha4Gal-T1 in P(1)+/- individuals did not reveal polymorphisms correlating with P(1)P(2) typing. ..
  2. Hellberg A, Ringressi A, Yahalom V, Säfwenberg J, Reid M, Olsson M. Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. Br J Haematol. 2004;125:528-36 pubmed
    ..The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. ..
  3. Iwamura K, Furukawa K, Uchikawa M, Sojka B, Kojima Y, Wiels J, et al. The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene. A clue to the solution of the P1/P2/p puzzle. J Biol Chem. 2003;278:44429-38 pubmed
    ..We analyzed the potential of the cloned Gb3/CD77 synthase to synthesize P1 antigen, because Gb3/CD77 and P1 share a common structure, Galalpha1,4Galbeta1,4Glc (NAc)-...
  4. Koda Y, Soejima M, Sato H, Maeda Y, Kimura H. Three-base deletion and one-base insertion of the alpha(1,4)galactosyltransferase gene responsible for the P phenotype. Transfusion. 2002;42:48-51 pubmed
    ..The P blood group phenotype is due to several distinct nonfunctional alleles without any predominant allele. ..
  5. Iwamura K, Uchikawa M, Sojka B, Wiels J, Okajima T, Urano T, et al. Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals. J Biol Chem. 2000;275:37752-6 pubmed
    ..To explore the molecular basis for this phenotype, DNA sequences of Gb3 synthase (alpha1, 4-galactosyltransferase; alpha1,4Gal-T) in six p phenotype individuals from Japan and Sweden were ..
  6. Yamaji T, Sekizuka T, Tachida Y, Sakuma C, Morimoto K, Kuroda M, et al. A CRISPR Screen Identifies LAPTM4A and TM9SF Proteins as Glycolipid-Regulating Factors. iScience. 2019;11:409-424 pubmed publisher
    ..Loss of LAPTM4A decreased endogenous Gb3 synthase activity in a post-transcriptional mechanism, whereas loss of TM9SF2 did not affect Gb3 synthase activity but ..
  7. Hattori T, Watanabe Takahashi M, Nishikawa K, Naito M. Acquired Resistance to Shiga Toxin-Induced Apoptosis by Loss of CD77 Expression in Human Myelogenous Leukemia Cell Line, THP-1. Biol Pharm Bull. 2018;41:1475-1479 pubmed publisher
    ..All of the ten resistant clones lost the expression of CD77 as a consequence of the reduction in CD77 synthase mRNA expression...
  8. Taguchi A, Maruyama H, Nameta M, Yamamoto T, Matsuda J, Kulkarni A, et al. A symptomatic Fabry disease mouse model generated by inducing globotriaosylceramide synthesis. Biochem J. 2013;456:373-83 pubmed publisher
    ..a symptomatic mouse model (G3Stg/GLAko) by cross-breeding GLAko mice with transgenic mice expressing human Gb3 synthase. G3Stg/GLAko mice had high Gb3 levels in major organs, and their serum Gb3 level at 5-25 weeks of age was 6-10-..
  9. Porubsky S, Speak A, Salio M, Jennemann R, Bonrouhi M, Zafarulla R, et al. Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells. J Immunol. 2012;189:3007-17 pubmed publisher
    ..In this study, we generate a globotrihexosylceramide (Gb3)-synthase-deficient (Gb3S(-/-)) mouse and show that in thymi of ?GalA(-/-)/Gb3S(-/-) double-knockout mice, which store isoglobosides but no ..

More Information

Publications40

  1. von Gerichten J, Schlosser K, Lamprecht D, Morace I, Eckhardt M, Wachten D, et al. Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals. J Lipid Res. 2017;58:1247-1258 pubmed publisher
    ..We further confirm β-GalCer as substrate of globotriaosylceramide synthase for galabiaosylceramide synthesis and identify additional members of the human gut microbiome to ..
  2. Kawai M, Obara K, Onodera T, Enomoto T, Ogasawara K, Tsuneyama H, et al. Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype. Transfusion. 2017;57:1072-1077 pubmed publisher
    ..The prevalence of the In(Lu) phenotype in the Japanese population was 0.02%, and we identified 13 known and 21 novel KLF1 alleles. The KLF1 mutations cause the reduced expression of the P1 antigen. ..
  3. Khan F, Pandian V, Ramraj S, Natarajan M, Aravindan S, Herman T, et al. Acquired genetic alterations in tumor cells dictate the development of high-risk neuroblastoma and clinical outcomes. BMC Cancer. 2015;15:514 pubmed publisher
  4. Jacob F, Alam S, Konantz M, Liang C, Kohler R, Everest Dass A, et al. Transition of Mesenchymal and Epithelial Cancer Cells Depends on ?1-4 Galactosyltransferase-Mediated Glycosphingolipids. Cancer Res. 2018;78:2952-2965 pubmed publisher
    ..b>Significance: This study highlights the essential role of glycosphingolipids in the maintenance of epithelial cancer cell properties. Cancer Res; 78(11); 2952-65. ©2018 AACR. ..
  5. Westman J, Stenfelt L, Vidovic K, Möller M, Hellberg Ã, Kjellström S, et al. Allele-selective RUNX1 binding regulates P1 blood group status by transcriptional control of A4GALT. Blood. 2018;: pubmed publisher
    ..These data indicate that RUNX1 regulates A4GALT and thereby the expression of clinically important glycosphingolipids implicated in blood-group incompatibility and host-pathogen interactions. ..
  6. Ando R, Tokuda N, Yamamoto T, Ikeda K, Hashimoto N, Taguchi R, et al. Immunization of A4galt-deficient mice with glycosphingolipids from renal cell cancers resulted in the generation of anti-sulfoglycolipid monoclonal antibodies. Glycoconj J. 2016;33:169-80 pubmed publisher
    In this study, we immunized Gb3/CD77 synthase gene (A4galt) knockout (KO) mice with glycosphingolipids (GSLs) extracted from 3 renal cell cancer (RCC) cell lines to raise monoclonal antibodies (mAbs) reactive with globo-series GSLs ..
  7. Maruyama H, Taguchi A, Nishikawa Y, Guili C, Mikame M, Nameta M, et al. Medullary thick ascending limb impairment in the GlatmTg(CAG-A4GALT) Fabry model mice. FASEB J. 2018;32:4544-4559 pubmed publisher
    ..levels, we previously crossbred asymptomatic Glatm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the GlatmTg(CAG-A4GALT) symptomatic Fabry model mice...
  8. Müller S, Wilhelm I, Schubert T, Zittlau K, Imberty A, Madl J, et al. Gb3-binding lectins as potential carriers for transcellular drug delivery. Expert Opin Drug Deliv. 2017;14:141-153 pubmed publisher
    ..We utilized an in vitro model based on Madin-Darby canine kidney cells transfected with Gb3 synthase to characterize transcytosis of the Gb3-binding lectins LecA from Pseudomonas aeruginosa and the B-subunit of ..
  9. Okuda T, Nakayama K. Identification and characterization of the human Gb3/CD77 synthase gene promoter. Glycobiology. 2008;18:1028-35 pubmed publisher
    ..The increased expression of Gb3 is due to the transcriptional upregulation of Gb3/CD77 synthase gene (Gb3S, also known as alpha1,4-galactosyltransferase gene), the mechanism of which still remains unknown...
  10. Kaczmarek R, Duk M, Szymczak K, Korchagina E, Tyborowska J, Mikolajczyk K, et al. Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating P(k), P1 and NOR blood group antigens. Biochem Biophys Res Commun. 2016;470:168-174 pubmed publisher
    Human Gb3/CD77 synthase (?1,4-galactosyltransferase, P(k) synthase), encoded by A4GALT gene, is known for synthesis of Gal(?1-4)Gal moiety in globotriaosylceramide (Gb3Cer, CD77, P(k) blood group antigen), a glycosphingolipid of the ..
  11. Wang Y, Chang C, Lin H, Lin K, Lin K, Hung C, et al. Functional characterisation of a complex mutation in the ?(1,4)galactosyltransferase gene in Taiwanese individuals with p phenotype. Transfus Med. 2011;21:84-9 pubmed publisher
    ..The first case of p phenotype in Taiwan was caused by a non-functional allele resulting from a homozygous complex mutation of A4GALT gene. ..
  12. Keusch J, Manzella S, Nyame K, Cummings R, Baenziger J. Cloning of Gb3 synthase, the key enzyme in globo-series glycosphingolipid synthesis, predicts a family of alpha 1, 4-glycosyltransferases conserved in plants, insects, and mammals. J Biol Chem. 2000;275:25315-21 pubmed
    ..Gb(3) glycolipid, also called P(k) antigen or CD77, is a known receptor for verotoxins. CHO cells that do not express Gb(3) and are resistant to verotoxin become susceptible to the toxin following transfection with Gb(3) synthase cDNA. ..
  13. Westman J, Hellberg A, Peyrard T, Thuresson B, Olsson M. Large deletions involving the regulatory upstream regions of A4GALT give rise to principally novel P1PK-null alleles. Transfusion. 2014;54:1831-5 pubmed publisher
    ..Furthermore, analysis of these regions will improve genetic blood group prediction. ..
  14. Thuresson B, Westman J, Olsson M. Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups. Blood. 2011;117:678-87 pubmed publisher
    ..Thus, P(1) zygosity partially explains the well-known interindividual variation in P1 strength. Future investigations need to focus on regulatory mechanisms underlying P1 synthesis. ..
  15. Li X, Diao X, Xia X, Hong X, Zhu F. A novel mutation in A4GALT was identified in a Chinese individual with p phenotype. Transfusion. 2017;57:215-216 pubmed publisher
  16. Furukawa K, Yokoyama K, Sato T, Wiels J, Hirayama Y, Ohta M, et al. Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins. J Biol Chem. 2002;277:11247-54 pubmed
    Expression levels of Gb3/CD77 synthase together with Gb3/CD77 antigen were analyzed using human hematopoietic tumor cell lines and normal cells...
  17. Hellberg A, Chester M, Olsson M. Two previously proposed P1/P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen. BMC Genet. 2005;6:49 pubmed
    ..None of the novel polymorphisms reported in this study correlated with P1/P2 status and the P1/p mystery remains unsolved. ..
  18. Paschke E, Fauler G, Winkler H, Schlagenhauf A, Plecko B, Erwa W, et al. Urinary total globotriaosylceramide and isoforms to identify women with Fabry disease: a diagnostic test study. Am J Kidney Dis. 2011;57:673-81 pubmed publisher
    ..We evaluated urinary total globotriaosylceramide (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female patients with and without chronic kidney disease (CKD)...
  19. Kaczmarek R, Mikolajewicz K, Szymczak K, Duk M, Majorczyk E, Krop Watorek A, et al. Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase. Glycoconj J. 2016;33:963-973 pubmed
    Human Gb3/CD77 synthase (?1,4-galactosyltransferase) is the only known glycosyltransferase that changes acceptor specificity because of a point mutation...
  20. Maria Cherian R, Gaunitz S, Nilsson A, Liu J, Karlsson N, Holgersson J. Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. Glycobiology. 2014;24:26-38 pubmed publisher
    ..P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. ..
  21. Shin I, Ishii S, Shin J, Sung K, Park B, Jang H, et al. Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression. BMB Rep. 2009;42:310-4 pubmed
    ..Gb3 content in the HLCC lines corresponded with Stxs-induced cytotoxicity as well as Gb3 synthase expression, but no correlation with Gb4 content was noted...
  22. Suchanowska A, Kaczmarek R, Duk M, Lukasiewicz J, Smolarek D, Majorczyk E, et al. A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome. J Biol Chem. 2012;287:38220-30 pubmed publisher
    ..responsible for the biosynthesis of Gal(?1-4)GalNAc, we identified a mutation in the A4GALT gene encoding Gb3/CD77 synthase (?1,4-galactosyltransferase)...
  23. Lund N, Olsson M, Ramkumar S, Sakac D, Yahalom V, Levene C, et al. The human P(k) histo-blood group antigen provides protection against HIV-1 infection. Blood. 2009;113:4980-91 pubmed publisher
    ..We conclude that P(k) expression strongly influences susceptibility to HIV-1 infection, which implicates P(k) as a new endogenous cell-surface factor that may provide protection against HIV-1 infection. ..
  24. Lai Y, Wu W, Yang C, Yang L, Chu C, Chan Y, et al. A systematic study of single-nucleotide polymorphisms in the A4GALT gene suggests a molecular genetic basis for the P1/P2 blood groups. Transfusion. 2014;54:3222-31 pubmed publisher
  25. Zumbrun S, Hanson L, Sinclair J, Freedy J, Melton Celsa A, Rodriguez Canales J, et al. Human intestinal tissue and cultured colonic cells contain globotriaosylceramide synthase mRNA and the alternate Shiga toxin receptor globotetraosylceramide. Infect Immun. 2010;78:4488-99 pubmed publisher
    ..by quantitative real-time PCR (qRT-PCR) that both fresh colonic epithelial sections and HCT-8 cells express Gb3 synthase mRNA...
  26. Ma K, Lan X, Xu X, Hong X, Chen S, Liu Y, et al. [Molecular basis for an individual with rare p phenotype in P1Pk blood group system]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2015;32:250-3 pubmed publisher
    To explore the molecular basis for an individual with rare p phenotype in the P1Pk blood group system...
  27. Hellberg A, Schmidt Melbye A, Reid M, Olsson M. Expression of a novel missense mutation found in the A4GALT gene of Amish individuals with the p phenotype. Transfusion. 2008;48:479-87 pubmed
    ..A novel A4GALT missense mutation causes the p phenotype in Amish individuals. ..
  28. Shiozuka C, Taguchi A, Matsuda J, Noguchi Y, Kunieda T, Uchio Yamada K, et al. Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease. J Biochem. 2011;149:161-70 pubmed publisher
    ..the Gb3 levels in mouse organs, we created transgenic mice (TgG3S) expressing human ?1,4-galactosyltransferase (Gb3 synthase). High levels of Gb3 were observed in all major organs of the TgG3S mouse...
  29. Yamaji T, Nishikawa K, Hanada K. Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturbs a trans-Golgi network enzyme, Gb3 synthase, and reduces Gb3 biosynthesis. J Biol Chem. 2010;285:35505-18 pubmed publisher
    ..The change of glycolipid composition was restored by overexpression of Gb3 synthase, suggesting that the synthase is affected by GRINA-C and FAIM2...
  30. Kojima Y, Fukumoto S, Okajima T, Wiels J, Yokoyama K, Suzuki Y, et al. Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem. 2000;275:15152-6 pubmed
    The expression cloning of a cDNA for globotriaosylceramide (Gb3)/CD77 synthase (alpha1,4-galactosyltransferase) was achieved using an anti-Gb3 antibody and mouse L cells as a recipient cell line for the transfection...
  31. Westman J, Hellberg A, Peyrard T, Hustinx H, Thuresson B, Olsson M. P1/P2 genotyping of known and novel null alleles in the P1PK and GLOB histo-blood group systems. Transfusion. 2013;53:2928-39 pubmed publisher
    The rare but clinically important null phenotypes of the P1PK and GLOB blood group systems are due to alterations in A4GALT and B3GALNT1, respectively...