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P17050 (NAGAB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-N-acetylgalactosaminidase

EC=3.2.1.49
Alternative name(s):
Alpha-galactosidase B
Gene names
Name:NAGA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids. Ref.9

Catalytic activity

Cleavage of non-reducing alpha-(1->3)-N-acetylgalactosamine residues from human blood group A and AB mucin glycoproteins, Forssman hapten and blood group A lacto series glycolipids. Ref.12

Subunit structure

Homodimer. Ref.12

Subcellular location

Lysosome.

Involvement in disease

Schindler disease (SCHIND) [MIM:609241]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.15

Kanzaki disease (KANZD) [MIM:609242]: Autosomal recessive disorder characterized by late-onset, angiokeratoma corporis diffusum and mild intellectual impairment.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.16

Miscellaneous

Alpha-galactosidase B was first found to be an isoenzyme of alpha-galactosidases, but apparently it differs from alpha-galactosidase A in substrate specificity and is alpha-N-acetylgalactosaminidase.

Sequence similarities

Belongs to the glycosyl hydrolase 27 family.

Sequence caution

The sequence AAA59902.1 differs from that shown. Reason: Frameshift at position 320.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.8
Chain18 – 411394Alpha-N-acetylgalactosaminidase
PRO_0000001018

Regions

Region78 – 792Substrate binding

Sites

Active site1561Nucleophile
Active site2171Proton donor
Binding site1541Substrate
Binding site1881Substrate
Binding site2131Substrate
Binding site2171Substrate

Amino acid modifications

Modified residue3221Phosphoserine Ref.10
Modified residue3321Phosphoserine Ref.10
Glycosylation1241N-linked (GlcNAc...) Ref.12
Glycosylation1771N-linked (GlcNAc...) Ref.11 Ref.12
Glycosylation2011N-linked (GlcNAc...) Ref.11
Glycosylation3591N-linked (GlcNAc...) Potential
Glycosylation3851N-linked (GlcNAc...) Ref.12
Disulfide bond38 ↔ 80 Ref.12
Disulfide bond42 ↔ 49 Ref.12
Disulfide bond127 ↔ 158 Ref.12
Disulfide bond187 ↔ 209 Ref.12

Natural variations

Natural variant1601S → C in SCHIND; type III. Ref.15
Corresponds to variant rs121434532 [ dbSNP | Ensembl ].
VAR_000496
Natural variant3251E → K in SCHIND; type I and type III. Ref.13 Ref.15
VAR_000497
Natural variant3291R → Q in KANZD. Ref.16
Corresponds to variant rs121434533 [ dbSNP | Ensembl ].
VAR_022525
Natural variant3291R → W in KANZD; loss of activity. Ref.14
VAR_000498

Experimental info

Mutagenesis2011N → Q: Loss of glycosylation site; no effect on enzyme activity and stability. Ref.12
Sequence conflict241Q → N AA sequence Ref.8
Sequence conflict1651R → A in AAA59902. Ref.2
Sequence conflict1751A → G in AAA59902. Ref.2
Sequence conflict2051L → Q in AAA59902. Ref.2

Secondary structure

.................................................................................. 411
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P17050 [UniParc].

Last modified March 1, 1992. Version 2.
Checksum: 781A0728C0B29CD9

FASTA41146,565
        10         20         30         40         50         60 
MLLKTVLLLG HVAQVLMLDN GLLQTPPMGW LAWERFRCNI NCDEDPKNCI SEQLFMEMAD 

        70         80         90        100        110        120 
RMAQDGWRDM GYTYLNIDDC WIGGRDASGR LMPDPKRFPH GIPFLADYVH SLGLKLGIYA 

       130        140        150        160        170        180 
DMGNFTCMGY PGTTLDKVVQ DAQTFAEWKV DMLKLDGCFS TPEERAQGYP KMAAALNATG 

       190        200        210        220        230        240 
RPIAFSCSWP AYEGGLPPRV NYSLLADICN LWRNYDDIQD SWWSVLSILN WFVEHQDILQ 

       250        260        270        280        290        300 
PVAGPGHWND PDMLLIGNFG LSLEQSRAQM ALWTVLAAPL LMSTDLRTIS AQNMDILQNP 

       310        320        330        340        350        360 
LMIKINQDPL GIQGRRIHKE KSLIEVYMRP LSNKASALVF FSCRTDMPYR YHSSLGQLNF 

       370        380        390        400        410 
TGSVIYEAQD VYSGDIISGL RDETNFTVII NPSGVVMWYL YPIKNLEMSQ Q 

« Hide

References

« Hide 'large scale' references
[1]"Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide sequence, and expression of a full-length cDNA. Homology with human alpha-galactosidase A suggests evolution from a common ancestral gene."
Wang A.M., Bishop D.F., Desnick R.J.
J. Biol. Chem. 265:21859-21866(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Lung.
[2]"Structural organization and complete sequence of the human alpha-N-acetylgalactosaminidase gene: homology with the alpha-galactosidase A gene provides evidence for evolution from a common ancestral gene."
Wang A.M., Desnick R.J.
Genomics 10:133-142(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Molecular cloning of a full-length cDNA for human alpha-N-acetylgalactosaminidase (alpha-galactosidase B)."
Tsuji S., Yamauchi T., Hiraiwa M., Isobe T., Okuyama T., Sakimura K., Takahashi Y., Nishizawa M., Uda Y., Miyatake T.
Biochem. Biophys. Res. Commun. 163:1498-1504(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[4]"Molecular cloning of two species of cDNAs for human alpha-N-acetylgalactosaminidase and expression in mammalian cells."
Yamauchi T., Hiraiwa M., Kobayashi H., Uda Y., Miyatake T., Tsuji S.
Biochem. Biophys. Res. Commun. 170:231-237(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[8]"Photolabeling of the alpha-neuraminidase/beta-galactosidase complex from human placenta with a photoreactive neuraminidase inhibitor."
Warner T.G., Louie A., Potier M.
Biochem. Biophys. Res. Commun. 173:13-19(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-37.
Tissue: Placenta.
[9]"Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts."
Asfaw B., Schindler D., Ledvinova J., Cerny B., Smid F., Conzelmann E.
J. Lipid Res. 39:1768-1780(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction."
Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.
Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322 AND SER-332, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[11]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-177 AND ASN-201.
Tissue: Liver.
[12]"The 1.9 A structure of human alpha-N-acetylgalactosaminidase: the molecular basis of Schindler and Kanzaki diseases."
Clark N.E., Garman S.C.
J. Mol. Biol. 393:435-447(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 18-411 IN COMPLEXES WITH N-ACETYLGALACTOSAMINE AND GALACTOSE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-124; ASN-177 AND ASN-385, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF ASN-201.
[13]"Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy."
Wang A.M., Schindler D., Desnick R.J.
J. Clin. Invest. 86:1752-1756(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCHIND LYS-325.
[14]"The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria."
Wang A.M., Kanzaki T., Desnick R.J.
J. Clin. Invest. 94:839-845(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT KANZD TRP-329, CHARACTERIZATION OF VARIANT KANZD TRP-329.
[15]"Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype."
Keulemans J.L.M., Reuser A.J.J., Kroos M.A., Willemsen R., Hermans M.M.P., van den Ouweland A.M.W., de Jong J.G.N., Wevers R.A., Renier W.O., Schindler D., Coll M.J., Chabas A., Sakuraba H., Suzuki Y., van Diggelen O.P.
J. Med. Genet. 33:458-464(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCHIND CYS-160 AND LYS-325.
[16]"A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation."
Kodama K., Kobayashi H., Abe R., Ohkawara A., Yoshii N., Yotsumoto S., Fukushige T., Nagatsuka Y., Hirabayashi Y., Kanzaki T.
Br. J. Dermatol. 144:363-368(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT KANZD GLN-329.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M62783 mRNA. Translation: AAA51677.1.
M59199 Genomic DNA. Translation: AAB06718.1.
M29276 mRNA. Translation: AAA59902.1. Frameshift.
M38083 mRNA. Translation: AAA36351.1.
CR456527 mRNA. Translation: CAG30413.1.
Z99716 Genomic DNA. Translation: CAB41237.1.
BC000095 mRNA. Translation: AAH00095.1.
CCDSCCDS14030.1.
PIRA33265.
A35485. A36530.
RefSeqNP_000253.1. NM_000262.2.
XP_005261672.1. XM_005261615.2.
XP_005261673.1. XM_005261616.2.
UniGeneHs.75372.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3H53X-ray2.01A/B18-411[»]
3H54X-ray2.20A/B18-411[»]
3H55X-ray1.91A/B18-411[»]
3IGUX-ray2.15A/B18-411[»]
4DO4X-ray1.40A/B18-411[»]
4DO5X-ray1.51A/B18-411[»]
4DO6X-ray1.60A/B18-411[»]
ProteinModelPortalP17050.
SMRP17050. Positions 18-411.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110749. 3 interactions.
STRING9606.ENSP00000379680.

Chemistry

ChEMBLCHEMBL3132.

Protein family/group databases

CAZyGH27. Glycoside Hydrolase Family 27.

PTM databases

PhosphoSiteP17050.
UniCarbKBP17050.

Polymorphism databases

DMDM127801.

Proteomic databases

MaxQBP17050.
PaxDbP17050.
PeptideAtlasP17050.
PRIDEP17050.

Protocols and materials databases

DNASU4668.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000396398; ENSP00000379680; ENSG00000198951.
ENST00000402937; ENSP00000384603; ENSG00000198951.
ENST00000403363; ENSP00000385283; ENSG00000198951.
GeneID4668.
KEGGhsa:4668.
UCSCuc003bbw.4. human.

Organism-specific databases

CTD4668.
GeneCardsGC22M042428.
HGNCHGNC:7631. NAGA.
HPAHPA000649.
MIM104170. gene.
609241. phenotype.
609242. phenotype.
neXtProtNX_P17050.
Orphanet79279. Alpha-N-acetylgalactosaminidase deficiency type 1.
79280. Alpha-N-acetylgalactosaminidase deficiency type 2.
79281. Alpha-N-acetylgalactosaminidase deficiency type 3.
PharmGKBPA31435.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68897.
HOGENOMHOG000161224.
HOVERGENHBG001989.
InParanoidP17050.
KOK01204.
OMAVIYEAQD.
OrthoDBEOG7F24SV.
PhylomeDBP17050.
TreeFamTF312909.

Enzyme and pathway databases

BioCycMetaCyc:HS01993-MONOMER.
SABIO-RKP17050.

Gene expression databases

BgeeP17050.
CleanExHS_NAGA.
GenevestigatorP17050.

Family and domain databases

Gene3D2.60.40.1180. 1 hit.
3.20.20.70. 1 hit.
InterProIPR013785. Aldolase_TIM.
IPR013780. Glyco_hydro_13_b.
IPR002241. Glyco_hydro_27.
IPR000111. Glyco_hydro_GHD.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PfamPF02065. Melibiase. 1 hit.
[Graphical view]
PRINTSPR00740. GLHYDRLASE27.
SUPFAMSSF51445. SSF51445. 1 hit.
PROSITEPS00512. ALPHA_GALACTOSIDASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP17050.
GeneWikiNAGA_(gene).
GenomeRNAi4668.
NextBio17986.
PROP17050.
SOURCESearch...

Entry information

Entry nameNAGAB_HUMAN
AccessionPrimary (citable) accession number: P17050
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries