ID NAGAB_HUMAN Reviewed; 411 AA. AC P17050; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-1992, sequence version 2. DT 27-MAR-2024, entry version 221. DE RecName: Full=Alpha-N-acetylgalactosaminidase {ECO:0000305}; DE EC=3.2.1.49 {ECO:0000269|PubMed:19683538}; DE AltName: Full=Alpha-galactosidase B; DE Flags: Precursor; GN Name=NAGA {ECO:0000312|HGNC:HGNC:7631}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Lung; RX PubMed=2174888; DOI=10.1016/s0021-9258(18)45818-8; RA Wang A.M., Bishop D.F., Desnick R.J.; RT "Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide RT sequence, and expression of a full-length cDNA. Homology with human alpha- RT galactosidase A suggests evolution from a common ancestral gene."; RL J. Biol. Chem. 265:21859-21866(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1646157; DOI=10.1016/0888-7543(91)90493-x; RA Wang A.M., Desnick R.J.; RT "Structural organization and complete sequence of the human alpha-N- RT acetylgalactosaminidase gene: homology with the alpha-galactosidase A gene RT provides evidence for evolution from a common ancestral gene."; RL Genomics 10:133-142(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=2551294; DOI=10.1016/0006-291x(89)91149-2; RA Tsuji S., Yamauchi T., Hiraiwa M., Isobe T., Okuyama T., Sakimura K., RA Takahashi Y., Nishizawa M., Uda Y., Miyatake T.; RT "Molecular cloning of a full-length cDNA for human alpha-N- RT acetylgalactosaminidase (alpha-galactosidase B)."; RL Biochem. Biophys. Res. Commun. 163:1498-1504(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2372288; DOI=10.1016/0006-291x(90)91264-s; RA Yamauchi T., Hiraiwa M., Kobayashi H., Uda Y., Miyatake T., Tsuji S.; RT "Molecular cloning of two species of cDNAs for human alpha-N- RT acetylgalactosaminidase and expression in mammalian cells."; RL Biochem. Biophys. Res. Commun. 170:231-237(1990). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 18-37. RC TISSUE=Placenta; RX PubMed=2256909; DOI=10.1016/s0006-291x(05)81014-9; RA Warner T.G., Louie A., Potier M.; RT "Photolabeling of the alpha-neuraminidase/beta-galactosidase complex from RT human placenta with a photoreactive neuraminidase inhibitor."; RL Biochem. Biophys. Res. Commun. 173:13-19(1990). RN [9] RP CATALYTIC ACTIVITY. RX PubMed=1418679; DOI=10.1515/bchm3.1992.373.2.989; RA Klima B., Pohlentz G., Schindler D., Egge H.; RT "An investigation into the glycolipid metabolism of alpha-N- RT acetylgalactosaminidase-deficient fibroblasts using native and artificial RT glycolipids."; RL Biol. Chem. Hoppe-Seyler 373:989-999(1992). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=9741689; RA Asfaw B., Schindler D., Ledvinova J., Cerny B., Smid F., Conzelmann E.; RT "Degradation of blood group A glycolipid A-6-2 by normal and mutant human RT skin fibroblasts."; RL J. Lipid Res. 39:1768-1780(1998). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322 AND SER-332, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17693683; DOI=10.1074/mcp.m700120-mcp200; RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., RA Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.; RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling RT network: indicating the involvement of ribonucleoside-diphosphate reductase RT M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal RT transduction."; RL Mol. Cell. Proteomics 6:1952-1967(2007). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-177 AND ASN-201. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 18-411 IN COMPLEXES WITH RP N-ACETYLGALACTOSAMINE AND GALACTOSE, DISULFIDE BONDS, GLYCOSYLATION AT RP ASN-124; ASN-177 AND ASN-385, SUBUNIT, CATALYTIC ACTIVITY, AND MUTAGENESIS RP OF ASN-201. RX PubMed=19683538; DOI=10.1016/j.jmb.2009.08.021; RA Clark N.E., Garman S.C.; RT "The 1.9 A structure of human alpha-N-acetylgalactosaminidase: the RT molecular basis of Schindler and Kanzaki diseases."; RL J. Mol. Biol. 393:435-447(2009). RN [15] RP VARIANT SCHIND LYS-325. RX PubMed=2243144; DOI=10.1172/jci114901; RA Wang A.M., Schindler D., Desnick R.J.; RT "Schindler disease: the molecular lesion in the alpha-N- RT acetylgalactosaminidase gene that causes an infantile neuroaxonal RT dystrophy."; RL J. Clin. Invest. 86:1752-1756(1990). RN [16] RP VARIANT KANZD TRP-329, AND CHARACTERIZATION OF VARIANT KANZD TRP-329. RX PubMed=8040340; DOI=10.1172/jci117404; RA Wang A.M., Kanzaki T., Desnick R.J.; RT "The molecular lesion in the alpha-N-acetylgalactosaminidase gene that RT causes angiokeratoma corporis diffusum with glycopeptiduria."; RL J. Clin. Invest. 94:839-845(1994). RN [17] RP VARIANTS SCHIND CYS-160 AND LYS-325. RX PubMed=8782044; DOI=10.1136/jmg.33.6.458; RA Keulemans J.L.M., Reuser A.J.J., Kroos M.A., Willemsen R., Hermans M.M.P., RA van den Ouweland A.M.W., de Jong J.G.N., Wevers R.A., Renier W.O., RA Schindler D., Coll M.J., Chabas A., Sakuraba H., Suzuki Y., RA van Diggelen O.P.; RT "Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new RT mutations and the paradox between genotype and phenotype."; RL J. Med. Genet. 33:458-464(1996). RN [18] RP VARIANT KANZD GLN-329. RX PubMed=11251574; DOI=10.1046/j.1365-2133.2001.04028.x; RA Kodama K., Kobayashi H., Abe R., Ohkawara A., Yoshii N., Yotsumoto S., RA Fukushige T., Nagatsuka Y., Hirabayashi Y., Kanzaki T.; RT "A new case of alpha-N-acetylgalactosaminidase deficiency with RT angiokeratoma corporis diffusum, with Meniere's syndrome and without mental RT retardation."; RL Br. J. Dermatol. 144:363-368(2001). CC -!- FUNCTION: Removes terminal alpha-N-acetylgalactosamine residues from CC glycolipids and glycopeptides. Required for the breakdown of CC glycolipids. {ECO:0000269|PubMed:9741689}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of non-reducing alpha-(1->3)-N-acetylgalactosamine CC residues from human blood group A and AB mucin glycoproteins, CC Forssman hapten and blood group A lacto series glycolipids.; CC EC=3.2.1.49; Evidence={ECO:0000269|PubMed:19683538}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a neolactoside IV(3)-alpha-GalNAc,IV(2)-alpha-Fuc- CC nLc4Cer(d18:1(4E)) + H2O = a neolactoside IV(2)-alpha-Fuc- CC nLc4Cer(d18:1(4E)) + N-acetyl-alpha-D-galactosamine; CC Xref=Rhea:RHEA:48212, ChEBI:CHEBI:15377, ChEBI:CHEBI:28471, CC ChEBI:CHEBI:28691, ChEBI:CHEBI:40356; CC Evidence={ECO:0000269|PubMed:9741689}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48213; CC Evidence={ECO:0000269|PubMed:9741689}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a neolactoside IV(3)-alpha-GalNAc,IV(2)-alpha-Fuc- CC nLc4Cer(d18:0) + H2O = a neolactoside IV(2)-alpha-Fuc-nLc4Cer(d18:0) CC + N-acetyl-alpha-D-galactosamine; Xref=Rhea:RHEA:49304, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:40356, ChEBI:CHEBI:91118, CC ChEBI:CHEBI:91119; Evidence={ECO:0000269|PubMed:9741689}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49305; CC Evidence={ECO:0000269|PubMed:9741689}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a globoside IV3GalNAc-Gb4Cer + H2O = a globoside Gb4Cer + N- CC acetyl-alpha-D-galactosamine; Xref=Rhea:RHEA:48412, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:40356, ChEBI:CHEBI:88167, CC ChEBI:CHEBI:90400; Evidence={ECO:0000269|PubMed:1418679}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48413; CC Evidence={ECO:0000269|PubMed:1418679}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19683538}. CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:9741689}. CC -!- DISEASE: Schindler disease (SCHIND) [MIM:609241]: Form of NAGA CC deficiency characterized by early-onset neuroaxonal dystrophy and CC neurological signs (convulsion during fever, epilepsy, psychomotor CC retardation and hypotonia). NAGA deficiency is typically classified in CC three main phenotypes: NAGA deficiency type I (Schindler disease or CC Schindler disease type I) with severe manifestations; NAGA deficiency CC type II (Kanzazi disease or Schindler disease type II) which is mild; CC NAGA deficiency type III (Schindler disease type III) characterized by CC mild-to-moderate neurologic manifestations. NAGA deficiency results in CC the increased urinary excretion of glycopeptides and oligosaccharides CC containing alpha-N-acetylgalactosaminyl moieties. Inheritance is CC autosomal recessive. {ECO:0000269|PubMed:2243144, CC ECO:0000269|PubMed:8782044}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Kanzaki disease (KANZD) [MIM:609242]: Autosomal recessive CC disorder characterized by late-onset, angiokeratoma corporis diffusum CC and mild intellectual impairment. {ECO:0000269|PubMed:11251574, CC ECO:0000269|PubMed:8040340}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Alpha-galactosidase B was first found to be an isoenzyme CC of alpha-galactosidases, but apparently it differs from alpha- CC galactosidase A in substrate specificity and is alpha-N- CC acetylgalactosaminidase. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 27 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA59902.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M62783; AAA51677.1; -; mRNA. DR EMBL; M59199; AAB06718.1; -; Genomic_DNA. DR EMBL; M29276; AAA59902.1; ALT_FRAME; mRNA. DR EMBL; M38083; AAA36351.1; -; mRNA. DR EMBL; CR456527; CAG30413.1; -; mRNA. DR EMBL; Z99716; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000095; AAH00095.1; -; mRNA. DR CCDS; CCDS14030.1; -. DR PIR; A33265; A33265. DR PIR; A36530; A35485. DR RefSeq; NP_000253.1; NM_000262.2. DR RefSeq; XP_005261672.1; XM_005261615.4. DR RefSeq; XP_005261673.1; XM_005261616.4. DR PDB; 3H53; X-ray; 2.01 A; A/B=18-411. DR PDB; 3H54; X-ray; 2.20 A; A/B=18-411. DR PDB; 3H55; X-ray; 1.91 A; A/B=18-411. DR PDB; 3IGU; X-ray; 2.15 A; A/B=18-411. DR PDB; 4DO4; X-ray; 1.40 A; A/B=18-411. DR PDB; 4DO5; X-ray; 1.51 A; A/B=18-411. DR PDB; 4DO6; X-ray; 1.60 A; A/B=18-411. DR PDBsum; 3H53; -. DR PDBsum; 3H54; -. DR PDBsum; 3H55; -. DR PDBsum; 3IGU; -. DR PDBsum; 4DO4; -. DR PDBsum; 4DO5; -. DR PDBsum; 4DO6; -. DR AlphaFoldDB; P17050; -. DR SMR; P17050; -. DR BioGRID; 110749; 90. DR IntAct; P17050; 3. DR MINT; P17050; -. DR STRING; 9606.ENSP00000379680; -. DR ChEMBL; CHEMBL3132; -. DR DrugBank; DB09462; Glycerin. DR SwissLipids; SLP:000001402; -. DR CAZy; GH27; Glycoside Hydrolase Family 27. DR GlyConnect; 45; 57 N-Linked glycans (2 sites). DR GlyCosmos; P17050; 5 sites, 84 glycans. DR GlyGen; P17050; 6 sites, 84 N-linked glycans (6 sites), 1 O-linked glycan (1 site). DR iPTMnet; P17050; -. DR PhosphoSitePlus; P17050; -. DR SwissPalm; P17050; -. DR BioMuta; NAGA; -. DR DMDM; 127801; -. DR CPTAC; CPTAC-2228; -. DR EPD; P17050; -. DR jPOST; P17050; -. DR MassIVE; P17050; -. DR MaxQB; P17050; -. DR PaxDb; 9606-ENSP00000379680; -. DR PeptideAtlas; P17050; -. DR ProteomicsDB; 53450; -. DR Pumba; P17050; -. DR Antibodypedia; 275; 216 antibodies from 23 providers. DR DNASU; 4668; -. DR Ensembl; ENST00000396398.8; ENSP00000379680.3; ENSG00000198951.12. DR Ensembl; ENST00000402937.1; ENSP00000384603.1; ENSG00000198951.12. DR Ensembl; ENST00000403363.5; ENSP00000385283.1; ENSG00000198951.12. DR GeneID; 4668; -. DR KEGG; hsa:4668; -. DR MANE-Select; ENST00000396398.8; ENSP00000379680.3; NM_000262.3; NP_000253.1. DR UCSC; uc003bbw.5; human. DR AGR; HGNC:7631; -. DR CTD; 4668; -. DR DisGeNET; 4668; -. DR GeneCards; NAGA; -. DR HGNC; HGNC:7631; NAGA. DR HPA; ENSG00000198951; Low tissue specificity. DR MalaCards; NAGA; -. DR MIM; 104170; gene. DR MIM; 609241; phenotype. DR MIM; 609242; phenotype. DR neXtProt; NX_P17050; -. DR OpenTargets; ENSG00000198951; -. DR Orphanet; 79279; Alpha-N-acetylgalactosaminidase deficiency type 1. DR Orphanet; 79280; Alpha-N-acetylgalactosaminidase deficiency type 2. DR Orphanet; 79281; Alpha-N-acetylgalactosaminidase deficiency type 3. DR PharmGKB; PA31435; -. DR VEuPathDB; HostDB:ENSG00000198951; -. DR eggNOG; KOG2366; Eukaryota. DR GeneTree; ENSGT00390000008751; -. DR HOGENOM; CLU_013093_0_0_1; -. DR InParanoid; P17050; -. DR OMA; DRYPPMR; -. DR OrthoDB; 1217107at2759; -. DR PhylomeDB; P17050; -. DR TreeFam; TF312909; -. DR BioCyc; MetaCyc:HS01993-MONOMER; -. DR BRENDA; 3.2.1.49; 2681. DR PathwayCommons; P17050; -. DR SABIO-RK; P17050; -. DR SignaLink; P17050; -. DR BioGRID-ORCS; 4668; 8 hits in 1165 CRISPR screens. DR ChiTaRS; NAGA; human. DR EvolutionaryTrace; P17050; -. DR GeneWiki; NAGA_(gene); -. DR GenomeRNAi; 4668; -. DR Pharos; P17050; Tbio. DR PRO; PR:P17050; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P17050; Protein. DR Bgee; ENSG00000198951; Expressed in monocyte and 171 other cell types or tissues. DR ExpressionAtlas; P17050; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0004557; F:alpha-galactosidase activity; IBA:GO_Central. DR GO; GO:0008456; F:alpha-N-acetylgalactosaminidase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0016052; P:carbohydrate catabolic process; IDA:UniProtKB. DR GO; GO:0019377; P:glycolipid catabolic process; IMP:UniProtKB. DR GO; GO:0016139; P:glycoside catabolic process; IBA:GO_Central. DR GO; GO:0009311; P:oligosaccharide metabolic process; IBA:GO_Central. DR CDD; cd14792; GH27; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR002241; Glyco_hydro_27. DR InterPro; IPR000111; Glyco_hydro_27/36_CS. DR InterPro; IPR013780; Glyco_hydro_b. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR InterPro; IPR035373; Melibiase/NAGA_C. DR PANTHER; PTHR11452; ALPHA-GALACTOSIDASE/ALPHA-N-ACETYLGALACTOSAMINIDASE; 1. DR PANTHER; PTHR11452:SF25; ALPHA-N-ACETYLGALACTOSAMINIDASE; 1. DR Pfam; PF16499; Melibiase_2; 1. DR Pfam; PF17450; Melibiase_2_C; 1. DR PRINTS; PR00740; GLHYDRLASE27. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. DR PROSITE; PS00512; ALPHA_GALACTOSIDASE; 1. DR Genevisible; P17050; HS. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; KW Epilepsy; Glycoprotein; Glycosidase; Hydrolase; Lipid metabolism; Lysosome; KW Phosphoprotein; Reference proteome; Signal. FT SIGNAL 1..17 FT /evidence="ECO:0000269|PubMed:2256909" FT CHAIN 18..411 FT /note="Alpha-N-acetylgalactosaminidase" FT /id="PRO_0000001018" FT ACT_SITE 156 FT /note="Nucleophile" FT ACT_SITE 217 FT /note="Proton donor" FT BINDING 78..79 FT /ligand="substrate" FT BINDING 154 FT /ligand="substrate" FT BINDING 188 FT /ligand="substrate" FT BINDING 213 FT /ligand="substrate" FT BINDING 217 FT /ligand="substrate" FT MOD_RES 322 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17693683" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17693683" FT CARBOHYD 124 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19683538" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19683538" FT CARBOHYD 201 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 359 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 385 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19683538" FT DISULFID 38..80 FT /evidence="ECO:0000269|PubMed:19683538" FT DISULFID 42..49 FT /evidence="ECO:0000269|PubMed:19683538" FT DISULFID 127..158 FT /evidence="ECO:0000269|PubMed:19683538" FT DISULFID 187..209 FT /evidence="ECO:0000269|PubMed:19683538" FT VARIANT 160 FT /note="S -> C (in SCHIND; type III; dbSNP:rs121434532)" FT /evidence="ECO:0000269|PubMed:8782044" FT /id="VAR_000496" FT VARIANT 325 FT /note="E -> K (in SCHIND; type I and type III; FT dbSNP:rs121434529)" FT /evidence="ECO:0000269|PubMed:2243144, FT ECO:0000269|PubMed:8782044" FT /id="VAR_000497" FT VARIANT 329 FT /note="R -> Q (in KANZD; dbSNP:rs121434533)" FT /evidence="ECO:0000269|PubMed:11251574" FT /id="VAR_022525" FT VARIANT 329 FT /note="R -> W (in KANZD; loss of activity; FT dbSNP:rs121434530)" FT /evidence="ECO:0000269|PubMed:8040340" FT /id="VAR_000498" FT MUTAGEN 201 FT /note="N->Q: Loss of glycosylation site; no effect on FT enzyme activity and stability." FT /evidence="ECO:0000269|PubMed:19683538" FT CONFLICT 24 FT /note="Q -> N (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 165 FT /note="R -> A (in Ref. 2; AAA59902)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="A -> G (in Ref. 2; AAA59902)" FT /evidence="ECO:0000305" FT CONFLICT 205 FT /note="L -> Q (in Ref. 2; AAA59902)" FT /evidence="ECO:0000305" FT STRAND 28..32 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 33..36 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 42..44 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 46..48 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 52..64 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 67..70 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 82..85 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 95..97 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 102..111 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 115..125 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 135..137 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 138..147 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 162..178 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 184..187 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 189..192 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 197..199 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 202..208 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 210..213 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 222..234 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 236..239 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 247..250 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 258..260 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 263..275 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 286..288 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 291..297 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 300..306 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 315..319 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 323..330 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 332..334 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 336..342 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 349..354 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 355..358 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 365..370 FT /evidence="ECO:0007829|PDB:4DO4" FT TURN 371..373 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 376..380 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 385..390 FT /evidence="ECO:0007829|PDB:4DO4" FT STRAND 395..403 FT /evidence="ECO:0007829|PDB:4DO4" FT HELIX 405..408 FT /evidence="ECO:0007829|PDB:4DO4" SQ SEQUENCE 411 AA; 46565 MW; 781A0728C0B29CD9 CRC64; MLLKTVLLLG HVAQVLMLDN GLLQTPPMGW LAWERFRCNI NCDEDPKNCI SEQLFMEMAD RMAQDGWRDM GYTYLNIDDC WIGGRDASGR LMPDPKRFPH GIPFLADYVH SLGLKLGIYA DMGNFTCMGY PGTTLDKVVQ DAQTFAEWKV DMLKLDGCFS TPEERAQGYP KMAAALNATG RPIAFSCSWP AYEGGLPPRV NYSLLADICN LWRNYDDIQD SWWSVLSILN WFVEHQDILQ PVAGPGHWND PDMLLIGNFG LSLEQSRAQM ALWTVLAAPL LMSTDLRTIS AQNMDILQNP LMIKINQDPL GIQGRRIHKE KSLIEVYMRP LSNKASALVF FSCRTDMPYR YHSSLGQLNF TGSVIYEAQD VYSGDIISGL RDETNFTVII NPSGVVMWYL YPIKNLEMSQ Q //