NAGAB_HUMAN
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 03-AUG-2022, entry version 212.
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=globoside IV3GalNAc-Gb4Cer + H2O = 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};
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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; 79.
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 GlyGen; P17050; 6 sites, 84 N-linked glycans (6 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P17050; -.
DR PhosphoSitePlus; 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; P17050; -.
DR PeptideAtlas; P17050; -.
DR PRIDE; P17050; -.
DR ProteomicsDB; 53450; -.
DR Antibodypedia; 275; 184 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 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; NAFGCDI; -.
DR OrthoDB; 964130at2759; -.
DR PhylomeDB; P17050; -.
DR TreeFam; TF312909; -.
DR BioCyc; MetaCyc:HS01993-MON; -.
DR BRENDA; 3.2.1.49; 2681.
DR PathwayCommons; P17050; -.
DR SABIO-RK; P17050; -.
DR SignaLink; P17050; -.
DR BioGRID-ORCS; 4668; 6 hits in 1082 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 169 other tissues.
DR ExpressionAtlas; P17050; baseline and differential.
DR Genevisible; P17050; HS.
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:0046477; P:glycosylceramide catabolic process; IBA:GO_Central.
DR GO; GO:0009311; P:oligosaccharide metabolic process; IBA:GO_Central.
DR CDD; cd14792; GH27; 1.
DR Gene3D; 2.60.40.1180; -; 1.
DR Gene3D; 3.20.20.70; -; 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; PTHR11452; 1.
DR Pfam; PF16499; Melibiase_2; 1.
DR Pfam; PF17450; Melibiase_2_C; 1.
DR PRINTS; PR00740; GLHYDRLASE27.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00512; ALPHA_GALACTOSIDASE; 1.
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
