3h55

Structural highlights

Disease

[NAGAB_HUMAN] Defects in NAGA are the cause of Schindler disease (SCHIND) [MIM:609241]. Schindler disease is a form of NAGA deficiency characterized by early onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.^{[1] [2]} Defects in NAGA are the cause of Kanzaki disease (KANZD) [MIM:609242]; also known as NAGA deficiency type II or Schindler disease type II. Kanzaki disease is an autosomal recessive disorder characterized by late onset, angiokeratoma corporis diffusum and mild intellectual impairment.^{[3] [4]}

Function

[NAGAB_HUMAN] Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids.^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Wang AM, Schindler D, Desnick R. Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. J Clin Invest. 1990 Nov;86(5):1752-6. PMID:2243144 doi:http://dx.doi.org/10.1172/JCI114901
2. ↑ Keulemans JL, Reuser AJ, Kroos MA, Willemsen R, Hermans MM, van den Ouweland AM, de Jong JG, Wevers RA, Renier WO, Schindler D, Coll MJ, Chabas A, Sakuraba H, Suzuki Y, van Diggelen OP. Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. J Med Genet. 1996 Jun;33(6):458-64. PMID:8782044
3. ↑ Wang AM, Kanzaki T, Desnick RJ. The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria. J Clin Invest. 1994 Aug;94(2):839-45. PMID:8040340 doi:http://dx.doi.org/10.1172/JCI117404
4. ↑ Kodama K, Kobayashi H, Abe R, Ohkawara A, Yoshii N, Yotsumoto S, Fukushige T, Nagatsuka Y, Hirabayashi Y, Kanzaki T. A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation. Br J Dermatol. 2001 Feb;144(2):363-8. PMID:11251574
5. ↑ Asfaw B, Schindler D, Ledvinova J, Cerny B, Smid F, Conzelmann E. Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts. J Lipid Res. 1998 Sep;39(9):1768-80. PMID:9741689
6. ↑ Clark NE, Garman SC. The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases. J Mol Biol. 2009 Oct 23;393(2):435-47. Epub 2009 Aug 14. PMID:19683538 doi:10.1016/j.jmb.2009.08.021