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Pathway Description
G(M2)-Gangliosidosis: Variant B, Tay-Sachs Disease
Homo sapiens
Disease Pathway
Created: 2013-08-29
Last Updated: 2019-08-21
GM2 gangliosidosis varient B or Tay-Sachs disease(TSD) is a neurodegenerative disorder which causes death in infantiles by age 5. Symptoms of TSD are present within 6 months of birth and include lack of motor development, mental retardation, seizures, and ultimately death. TSD is caused by the accumulation of GM2 gangliosides. Hexosaminadase A is the enzyme responsible for the degradation of GM2 gangliosides. It is a heterodimer made an alpha and beta subunit. The deficiency of this enzyme leads to the accumulation of GM2 gangliosides in neuronal lysosomes, eventually leading to cell death
References
G(M2)-Gangliosidosis: Variant B, Tay-Sachs Disease References
[Metagen: G(M2)-GANGLIOSIDOSIS: VARIANT B, TAY-SACHS DISEASE](http://metagene.de/program/d.prg?id_d=305)
[OMIM: 272800](http://omim.org/entry/272800})
[NIH](http://ghr.nlm.nih.gov/condition/tay-sachs-disease)
Gravel RA, Triggs-Raine BL, Mahuran DJ: Biochemistry and genetics of Tay-Sachs disease. Can J Neurol Sci. 1991 Aug;18(3 Suppl):419-23.
Pubmed: 1834320
Lawson CA, Martin DR: Animal models of GM2 gangliosidosis: utility and limitations. Appl Clin Genet. 2016 Jul 20;9:111-20. doi: 10.2147/TACG.S85354. eCollection 2016.
Pubmed: 27499644
Mark BL, Mahuran DJ, Cherney MM, Zhao D, Knapp S, James MN: Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. J Mol Biol. 2003 Apr 11;327(5):1093-109. doi: 10.1016/s0022-2836(03)00216-x.
Pubmed: 12662933
Daroff RB, Aminoff MJ. Encyclopedia of the Neurological Sciences. Academic Press; 2014.
Rosenberg RN, Rosenberg RN, Pascual JM. Rosenbergs molecular and genetic basis of neurological and psychiatric disease. London, England: Academic Press; 2015
Glycosphingolipid Biosynthesis - Ganglio Series References
Schnaar RL, Kinoshita T. Glycosphingolipids. 2017. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology [Internet]. 3rd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2015-2017. Chapter 11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK453016/ doi: 10.1101/glycobiology.3e.011
D'Angelo G, Capasso S, Sticco L, Russo D: Glycosphingolipids: synthesis and functions. FEBS J. 2013 Dec;280(24):6338-53. doi: 10.1111/febs.12559. Epub 2013 Oct 25.
Pubmed: 24165035
Groux-Degroote S, Guerardel Y, Delannoy P: Gangliosides: Structures, Biosynthesis, Analysis, and Roles in Cancer. Chembiochem. 2017 Jul 4;18(13):1146-1154. doi: 10.1002/cbic.201600705. Epub 2017 Apr 24.
Pubmed: 28295942
Nagata Y, Yamashiro S, Yodoi J, Lloyd KO, Shiku H, Furukawa K: Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. J Biol Chem. 1992 Jun 15;267(17):12082-9.
Pubmed: 1601877
Nagata Y, Yamashiro S, Yodoi J, Lloyd KO, Shiku H, Furukawa K: Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. J Biol Chem. 1994 Mar 4;269(9):7045.
Pubmed: 8120069
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Shiina T, Kikkawa E, Iwasaki H, Kaneko M, Narimatsu H, Sasaki K, Bahram S, Inoko H: The beta-1,3-galactosyltransferase-4 (B3GALT4) gene is located in the centromeric segment of the human MHC class II region. Immunogenetics. 2000 Jan;51(1):75-8.
Pubmed: 10663566
Amado M, Almeida R, Carneiro F, Levery SB, Holmes EH, Nomoto M, Hollingsworth MA, Hassan H, Schwientek T, Nielsen PA, Bennett EP, Clausen H: A family of human beta3-galactosyltransferases. Characterization of four members of a UDP-galactose:beta-N-acetyl-glucosamine/beta-nacetyl-galactosamine beta-1,3-galactosyltransferase family. J Biol Chem. 1998 May 22;273(21):12770-8. doi: 10.1074/jbc.273.21.12770.
Pubmed: 9582303
Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
Pubmed: 14574404
Kitagawa H, Paulson JC: Differential expression of five sialyltransferase genes in human tissues. J Biol Chem. 1994 Jul 8;269(27):17872-8.
Pubmed: 8027041
Chang ML, Eddy RL, Shows TB, Lau JT: Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal mapping studies. Glycobiology. 1995 May;5(3):319-25. doi: 10.1093/glycob/5.3.319.
Pubmed: 7655169
Shang J, Qiu R, Wang J, Liu J, Zhou R, Ding H, Yang S, Zhang S, Jin C: Molecular cloning and expression of Galbeta1,3GalNAc alpha2, 3-sialyltransferase from human fetal liver. Eur J Biochem. 1999 Oct;265(2):580-8. doi: 10.1046/j.1432-1327.1999.00733.x.
Pubmed: 10504389
Kim YJ, Kim KS, Do S, Kim CH, Kim SK, Lee YC: Molecular cloning and expression of human alpha2,8-sialyltransferase (hST8Sia V). Biochem Biophys Res Commun. 1997 Jun 18;235(2):327-30. doi: 10.1006/bbrc.1997.6725.
Pubmed: 9199191
Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. doi: 10.1038/nature03983.
Pubmed: 16177791
Ishii A, Ohta M, Watanabe Y, Matsuda K, Ishiyama K, Sakoe K, Nakamura M, Inokuchi J, Sanai Y, Saito M: Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase. J Biol Chem. 1998 Nov 27;273(48):31652-5. doi: 10.1074/jbc.273.48.31652.
Pubmed: 9822625
Berselli P, Zava S, Sottocornola E, Milani S, Berra B, Colombo I: Human GM3 synthase: a new mRNA variant encodes an NH2-terminal extended form of the protein. Biochim Biophys Acta. 2006 Jul;1759(7):348-58. doi: 10.1016/j.bbaexp.2006.07.001. Epub 2006 Jul 21.
Pubmed: 16934889
Sasaki K, Kurata K, Kojima N, Kurosawa N, Ohta S, Hanai N, Tsuji S, Nishi T: Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase). J Biol Chem. 1994 Jun 3;269(22):15950-6.
Pubmed: 8195250
Nara K, Watanabe Y, Maruyama K, Kasahara K, Nagai Y, Sanai Y: Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7952-6. doi: 10.1073/pnas.91.17.7952.
Pubmed: 8058740
Haraguchi M, Yamashiro S, Yamamoto A, Furukawa K, Takamiya K, Lloyd KO, Shiku H, Furukawa K: Isolation of GD3 synthase gene by expression cloning of GM3 alpha-2,8-sialyltransferase cDNA using anti-GD2 monoclonal antibody. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10455-9. doi: 10.1073/pnas.91.22.10455.
Pubmed: 7937974
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