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Protein

Alpha-N-acetylgalactosaminidase

Gene

NAGA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids.1 Publication

Catalytic activityi

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei154Substrate1
Active sitei156Nucleophile1
Binding sitei188Substrate1
Binding sitei213Substrate1
Active sitei217Proton donor1
Binding sitei217Substrate1

GO - Molecular functioni

  • alpha-galactosidase activity Source: GO_Central
  • alpha-N-acetylgalactosaminidase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • carbohydrate catabolic process Source: UniProtKB
  • glycolipid catabolic process Source: UniProtKB
  • glycoside catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS01993-MONOMER.
ZFISH:HS01993-MONOMER.
BRENDAi3.2.1.49. 2681.
SABIO-RKP17050.

Protein family/group databases

CAZyiGH27. Glycoside Hydrolase Family 27.

Chemistry databases

SwissLipidsiSLP:000001402.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-N-acetylgalactosaminidase (EC:3.2.1.49)
Alternative name(s):
Alpha-galactosidase B
Gene namesi
Name:NAGA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:7631. NAGA.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • lysosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Schindler disease (SCHIND)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionForm 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.
See also OMIM:609241
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000496160S → C in SCHIND; type III. 1 PublicationCorresponds to variant rs121434532dbSNPEnsembl.1
Natural variantiVAR_000497325E → K in SCHIND; type I and type III. 2 PublicationsCorresponds to variant rs121434529dbSNPEnsembl.1
Kanzaki disease (KANZD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disorder characterized by late-onset, angiokeratoma corporis diffusum and mild intellectual impairment.
See also OMIM:609242
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022525329R → Q in KANZD. 1 PublicationCorresponds to variant rs121434533dbSNPEnsembl.1
Natural variantiVAR_000498329R → W in KANZD; loss of activity. 1 PublicationCorresponds to variant rs121434530dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi201N → Q: Loss of glycosylation site; no effect on enzyme activity and stability. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi4668.
MalaCardsiNAGA.
MIMi609241. phenotype.
609242. phenotype.
OpenTargetsiENSG00000198951.
Orphaneti79279. Alpha-N-acetylgalactosaminidase deficiency type 1.
79280. Alpha-N-acetylgalactosaminidase deficiency type 2.
79281. Alpha-N-acetylgalactosaminidase deficiency type 3.
PharmGKBiPA31435.

Chemistry databases

ChEMBLiCHEMBL3132.

Polymorphism and mutation databases

BioMutaiNAGA.
DMDMi127801.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 171 PublicationAdd BLAST17
ChainiPRO_000000101818 – 411Alpha-N-acetylgalactosaminidaseAdd BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi38 ↔ 801 Publication
Disulfide bondi42 ↔ 491 Publication
Glycosylationi124N-linked (GlcNAc...)1 Publication1
Disulfide bondi127 ↔ 1581 Publication
Glycosylationi177N-linked (GlcNAc...)2 Publications1
Disulfide bondi187 ↔ 2091 Publication
Glycosylationi201N-linked (GlcNAc...)1 Publication1
Modified residuei322PhosphoserineCombined sources1
Modified residuei332PhosphoserineCombined sources1
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Glycosylationi385N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP17050.
MaxQBiP17050.
PaxDbiP17050.
PeptideAtlasiP17050.
PRIDEiP17050.

PTM databases

iPTMnetiP17050.
PhosphoSitePlusiP17050.
UniCarbKBiP17050.

Expressioni

Gene expression databases

BgeeiENSG00000198951.
CleanExiHS_NAGA.
ExpressionAtlasiP17050. baseline and differential.
GenevisibleiP17050. HS.

Organism-specific databases

HPAiHPA000649.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110749. 5 interactors.
STRINGi9606.ENSP00000379680.

Structurei

Secondary structure

1411
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 32Combined sources5
Helixi33 – 36Combined sources4
Turni42 – 44Combined sources3
Turni46 – 48Combined sources3
Beta strandi49 – 51Combined sources3
Helixi52 – 64Combined sources13
Helixi67 – 70Combined sources4
Beta strandi74 – 76Combined sources3
Beta strandi82 – 85Combined sources4
Beta strandi91 – 93Combined sources3
Turni95 – 97Combined sources3
Helixi102 – 111Combined sources10
Beta strandi115 – 125Combined sources11
Helixi135 – 137Combined sources3
Helixi138 – 147Combined sources10
Beta strandi152 – 156Combined sources5
Helixi162 – 178Combined sources17
Beta strandi184 – 187Combined sources4
Helixi189 – 192Combined sources4
Turni197 – 199Combined sources3
Helixi202 – 208Combined sources7
Beta strandi210 – 213Combined sources4
Helixi222 – 234Combined sources13
Helixi236 – 239Combined sources4
Helixi240 – 242Combined sources3
Beta strandi247 – 250Combined sources4
Beta strandi258 – 260Combined sources3
Helixi263 – 275Combined sources13
Beta strandi280 – 282Combined sources3
Turni286 – 288Combined sources3
Helixi291 – 297Combined sources7
Helixi300 – 306Combined sources7
Beta strandi315 – 319Combined sources5
Beta strandi323 – 330Combined sources8
Helixi332 – 334Combined sources3
Beta strandi336 – 342Combined sources7
Beta strandi345 – 347Combined sources3
Beta strandi349 – 354Combined sources6
Helixi355 – 358Combined sources4
Beta strandi365 – 370Combined sources6
Turni371 – 373Combined sources3
Beta strandi376 – 380Combined sources5
Beta strandi385 – 390Combined sources6
Beta strandi395 – 403Combined sources9
Helixi405 – 408Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP17050.
SMRiP17050.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17050.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 79Substrate binding2

Sequence similaritiesi

Belongs to the glycosyl hydrolase 27 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2366. Eukaryota.
ENOG410XPF1. LUCA.
GeneTreeiENSGT00390000008751.
HOGENOMiHOG000161224.
HOVERGENiHBG001989.
InParanoidiP17050.
KOiK01204.
OMAiFVEHQDI.
OrthoDBiEOG091G0BGV.
PhylomeDBiP17050.
TreeFamiTF312909.

Family and domain databases

CDDicd14792. GH27. 1 hit.
Gene3Di2.60.40.1180. 1 hit.
3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR002241. Glyco_hydro_27.
IPR000111. Glyco_hydro_27/36_CS.
IPR013780. Glyco_hydro_b.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PfamiPF16499. Melibiase_2. 1 hit.
[Graphical view]
PRINTSiPR00740. GLHYDRLASE27.
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00512. ALPHA_GALACTOSIDASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P17050-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLKTVLLLG HVAQVLMLDN GLLQTPPMGW LAWERFRCNI NCDEDPKNCI
60 70 80 90 100
SEQLFMEMAD RMAQDGWRDM GYTYLNIDDC WIGGRDASGR LMPDPKRFPH
110 120 130 140 150
GIPFLADYVH SLGLKLGIYA DMGNFTCMGY PGTTLDKVVQ DAQTFAEWKV
160 170 180 190 200
DMLKLDGCFS TPEERAQGYP KMAAALNATG RPIAFSCSWP AYEGGLPPRV
210 220 230 240 250
NYSLLADICN LWRNYDDIQD SWWSVLSILN WFVEHQDILQ PVAGPGHWND
260 270 280 290 300
PDMLLIGNFG LSLEQSRAQM ALWTVLAAPL LMSTDLRTIS AQNMDILQNP
310 320 330 340 350
LMIKINQDPL GIQGRRIHKE KSLIEVYMRP LSNKASALVF FSCRTDMPYR
360 370 380 390 400
YHSSLGQLNF TGSVIYEAQD VYSGDIISGL RDETNFTVII NPSGVVMWYL
410
YPIKNLEMSQ Q
Length:411
Mass (Da):46,565
Last modified:March 1, 1992 - v2
Checksum:i781A0728C0B29CD9
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24Q → N AA sequence (PubMed:2256909).Curated1
Sequence conflicti165R → A in AAA59902 (PubMed:1646157).Curated1
Sequence conflicti175A → G in AAA59902 (PubMed:1646157).Curated1
Sequence conflicti205L → Q in AAA59902 (PubMed:1646157).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000496160S → C in SCHIND; type III. 1 PublicationCorresponds to variant rs121434532dbSNPEnsembl.1
Natural variantiVAR_000497325E → K in SCHIND; type I and type III. 2 PublicationsCorresponds to variant rs121434529dbSNPEnsembl.1
Natural variantiVAR_022525329R → Q in KANZD. 1 PublicationCorresponds to variant rs121434533dbSNPEnsembl.1
Natural variantiVAR_000498329R → W in KANZD; loss of activity. 1 PublicationCorresponds to variant rs121434530dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS14030.1.
PIRiA33265.
A36530. A35485.
RefSeqiNP_000253.1. NM_000262.2.
XP_005261672.1. XM_005261615.4.
XP_005261673.1. XM_005261616.4.
UniGeneiHs.75372.

Genome annotation databases

EnsembliENST00000396398; ENSP00000379680; ENSG00000198951.
ENST00000402937; ENSP00000384603; ENSG00000198951.
ENST00000403363; ENSP00000385283; ENSG00000198951.
GeneIDi4668.
KEGGihsa:4668.
UCSCiuc003bbw.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS14030.1.
PIRiA33265.
A36530. A35485.
RefSeqiNP_000253.1. NM_000262.2.
XP_005261672.1. XM_005261615.4.
XP_005261673.1. XM_005261616.4.
UniGeneiHs.75372.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP17050.
SMRiP17050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110749. 5 interactors.
STRINGi9606.ENSP00000379680.

Chemistry databases

ChEMBLiCHEMBL3132.
SwissLipidsiSLP:000001402.

Protein family/group databases

CAZyiGH27. Glycoside Hydrolase Family 27.

PTM databases

iPTMnetiP17050.
PhosphoSitePlusiP17050.
UniCarbKBiP17050.

Polymorphism and mutation databases

BioMutaiNAGA.
DMDMi127801.

Proteomic databases

EPDiP17050.
MaxQBiP17050.
PaxDbiP17050.
PeptideAtlasiP17050.
PRIDEiP17050.

Protocols and materials databases

DNASUi4668.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000396398; ENSP00000379680; ENSG00000198951.
ENST00000402937; ENSP00000384603; ENSG00000198951.
ENST00000403363; ENSP00000385283; ENSG00000198951.
GeneIDi4668.
KEGGihsa:4668.
UCSCiuc003bbw.5. human.

Organism-specific databases

CTDi4668.
DisGeNETi4668.
GeneCardsiNAGA.
HGNCiHGNC:7631. NAGA.
HPAiHPA000649.
MalaCardsiNAGA.
MIMi104170. gene.
609241. phenotype.
609242. phenotype.
neXtProtiNX_P17050.
OpenTargetsiENSG00000198951.
Orphaneti79279. Alpha-N-acetylgalactosaminidase deficiency type 1.
79280. Alpha-N-acetylgalactosaminidase deficiency type 2.
79281. Alpha-N-acetylgalactosaminidase deficiency type 3.
PharmGKBiPA31435.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2366. Eukaryota.
ENOG410XPF1. LUCA.
GeneTreeiENSGT00390000008751.
HOGENOMiHOG000161224.
HOVERGENiHBG001989.
InParanoidiP17050.
KOiK01204.
OMAiFVEHQDI.
OrthoDBiEOG091G0BGV.
PhylomeDBiP17050.
TreeFamiTF312909.

Enzyme and pathway databases

BioCyciMetaCyc:HS01993-MONOMER.
ZFISH:HS01993-MONOMER.
BRENDAi3.2.1.49. 2681.
SABIO-RKP17050.

Miscellaneous databases

EvolutionaryTraceiP17050.
GeneWikiiNAGA_(gene).
GenomeRNAii4668.
PROiP17050.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198951.
CleanExiHS_NAGA.
ExpressionAtlasiP17050. baseline and differential.
GenevisibleiP17050. HS.

Family and domain databases

CDDicd14792. GH27. 1 hit.
Gene3Di2.60.40.1180. 1 hit.
3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR002241. Glyco_hydro_27.
IPR000111. Glyco_hydro_27/36_CS.
IPR013780. Glyco_hydro_b.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PfamiPF16499. Melibiase_2. 1 hit.
[Graphical view]
PRINTSiPR00740. GLHYDRLASE27.
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00512. ALPHA_GALACTOSIDASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNAGAB_HUMAN
AccessioniPrimary (citable) accession number: P17050
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 1, 1992
Last modified: November 2, 2016
This is version 179 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.