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Protein

Alpha-N-acetylgalactosaminidase

Gene

NAGA

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

Functioni

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

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.

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
  • glycosylceramide catabolic process Source: GO_Central
  • oligosaccharide metabolic process Source: GO_Central

Keywordsi

Molecular functionGlycosidase, Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000198951.11
HGNCiHGNC:7631 NAGA
MIMi104170 gene
neXtProtiNX_P17050

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs121434532EnsemblClinVar.1
Natural variantiVAR_000497325E → K in SCHIND; type I and type III. 2 PublicationsCorresponds to variant dbSNP:rs121434529EnsemblClinVar.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 dbSNP:rs121434533EnsemblClinVar.1
Natural variantiVAR_000498329R → W in KANZD; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121434530EnsemblClinVar.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
DrugBankiDB04077 Glycerol

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...) asparagine1 Publication1
Disulfide bondi127 ↔ 1581 Publication
Glycosylationi177N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi187 ↔ 2091 Publication
Glycosylationi201N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei322PhosphoserineCombined sources1
Modified residuei332PhosphoserineCombined sources1
Glycosylationi359N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi385N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP17050
MaxQBiP17050
PaxDbiP17050
PeptideAtlasiP17050
PRIDEiP17050

PTM databases

GlyConnecti45
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
OMAiDDLWDRW
OrthoDBiEOG091G0BGV
PhylomeDBiP17050
TreeFamiTF312909

Family and domain databases

CDDicd14792 GH27, 1 hit
Gene3Di2.60.40.1180, 1 hit
3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR002241 Glyco_hydro_27
IPR000111 Glyco_hydro_27/36_CS
IPR013780 Glyco_hydro_b
IPR017853 Glycoside_hydrolase_SF
IPR035373 Melibiase/NAGA_C
PfamiView protein in Pfam
PF16499 Melibiase_2, 1 hit
PF17450 Melibiase_2_C, 1 hit
PRINTSiPR00740 GLHYDRLASE27
SUPFAMiSSF51445 SSF51445, 1 hit
PROSITEiView protein in PROSITE
PS00512 ALPHA_GALACTOSIDASE, 1 hit

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 dbSNP:rs121434532EnsemblClinVar.1
Natural variantiVAR_000497325E → K in SCHIND; type I and type III. 2 PublicationsCorresponds to variant dbSNP:rs121434529EnsemblClinVar.1
Natural variantiVAR_022525329R → Q in KANZD. 1 PublicationCorresponds to variant dbSNP:rs121434533EnsemblClinVar.1
Natural variantiVAR_000498329R → W in KANZD; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121434530EnsemblClinVar.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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiNAGAB_HUMAN
AccessioniPrimary (citable) accession number: P17050
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 1, 1992
Last modified: April 25, 2018
This is version 189 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

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

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