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Protein

N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase

Gene

AGA

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

Functioni

Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.

Catalytic activityi

N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H2O = N-acetyl-beta-D-glucosaminylamine + L-aspartate.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei206Nucleophile1 Publication1

GO - Molecular functioni

  • N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity Source: UniProtKB
  • peptidase activity Source: UniProtKB-KW

GO - Biological processi

  • protein deglycosylation Source: UniProtKB
  • protein maturation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

Enzyme and pathway databases

BioCyciMetaCyc:HS00528-MONOMER.
ZFISH:HS00528-MONOMER.
BRENDAi3.5.1.26. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SABIO-RKP20933.

Protein family/group databases

MEROPSiT02.001.

Names & Taxonomyi

Protein namesi
Recommended name:
N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (EC:3.5.1.26)
Alternative name(s):
Aspartylglucosaminidase
Glycosylasparaginase
N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase
Cleaved into the following 2 chains:
Gene namesi
Name:AGA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:318. AGA.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Aspartylglucosaminuria (AGU)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inborn lysosomal storage disease causing excess accumulation of glycoasparagine in the body tissues and its increased excretion in urine. Clinical features include mild to severe mental retardation manifesting from the age of two, coarse facial features and mild connective tissue abnormalities.
See also OMIM:208400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01542712V → L in AGU; uncertain pathological significance. 1 PublicationCorresponds to variant rs74626221dbSNPEnsembl.1
Natural variantiVAR_00506960G → D in AGU. Corresponds to variant rs121964907dbSNPEnsembl.1
Natural variantiVAR_00507072S → P in AGU; specifically prevents the proteolytic activation cleavage of AGA in the endoplasmic reticulum. 1 PublicationCorresponds to variant rs121964909dbSNPEnsembl.1
Natural variantiVAR_015428100G → E in AGU. 1 PublicationCorresponds to variant rs386833421dbSNPEnsembl.1
Natural variantiVAR_005071101A → V in AGU. Corresponds to variant rs121964908dbSNPEnsembl.1
Natural variantiVAR_015429135F → S in AGU. 1 PublicationCorresponds to variant rs386833427dbSNPEnsembl.1
Natural variantiVAR_005072161R → Q in AGU. 3 PublicationsCorresponds to variant rs192195150dbSNPEnsembl.1
Natural variantiVAR_005073163C → S in AGU; most frequent mutation; abolishes autocatalytic cleavage and enzyme activity. 3 PublicationsCorresponds to variant rs121964904dbSNPEnsembl.1
Natural variantiVAR_015430252G → E in AGU. 1 PublicationCorresponds to variant rs386833433dbSNPEnsembl.1
Natural variantiVAR_015431252G → R in AGU. 1 PublicationCorresponds to variant rs386833432dbSNPEnsembl.1
Natural variantiVAR_015432257T → I in AGU. 1 PublicationCorresponds to variant rs386833434dbSNPEnsembl.1
Natural variantiVAR_005074302G → R in AGU. Corresponds to variant rs121964905dbSNPEnsembl.1
Natural variantiVAR_005075306C → R in AGU. Corresponds to variant rs121964906dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi175.
MalaCardsiAGA.
MIMi208400. phenotype.
OpenTargetsiENSG00000038002.
Orphaneti93. Aspartylglucosaminuria.
PharmGKBiPA24615.

Polymorphism and mutation databases

BioMutaiAGA.
DMDMi288558804.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Combined sources1 PublicationAdd BLAST23
ChainiPRO_000000233324 – 205Glycosylasparaginase alpha chainAdd BLAST182
ChainiPRO_0000002334206 – 346Glycosylasparaginase beta chainAdd BLAST141

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24Blocked amino end (Ser)1
Glycosylationi38N-linked (GlcNAc...)3 Publications1
Disulfide bondi64 ↔ 691 Publication
Disulfide bondi163 ↔ 1791 Publication
Disulfide bondi286 ↔ 3061 Publication
Glycosylationi308N-linked (GlcNAc...)1 Publication1
Disulfide bondi317 ↔ 3451 Publication

Post-translational modificationi

Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein

Proteomic databases

EPDiP20933.
MaxQBiP20933.
PaxDbiP20933.
PeptideAtlasiP20933.
PRIDEiP20933.

PTM databases

iPTMnetiP20933.
PhosphoSitePlusiP20933.

Miscellaneous databases

PMAP-CutDBP20933.

Expressioni

Gene expression databases

BgeeiENSG00000038002.
CleanExiHS_AGA.
ExpressionAtlasiP20933. baseline and differential.
GenevisibleiP20933. HS.

Organism-specific databases

HPAiHPA031415.
HPA031417.

Interactioni

Subunit structurei

Heterotetramer of two alpha and two beta chains arranged as a dimer of alpha/beta heterodimers.1 Publication

Protein-protein interaction databases

BioGridi106683. 8 interactors.
IntActiP20933. 2 interactors.
STRINGi9606.ENSP00000264595.

Chemistry databases

BindingDBiP20933.

Structurei

Secondary structure

1346
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 35Combined sources8
Helixi37 – 48Combined sources12
Helixi53 – 67Combined sources15
Helixi69 – 71Combined sources3
Beta strandi72 – 77Combined sources6
Beta strandi87 – 93Combined sources7
Turni94 – 96Combined sources3
Beta strandi99 – 105Combined sources7
Beta strandi107 – 109Combined sources3
Helixi111 – 121Combined sources11
Beta strandi125 – 128Combined sources4
Helixi129 – 138Combined sources10
Helixi149 – 160Combined sources12
Turni175 – 177Combined sources3
Beta strandi207 – 212Combined sources6
Beta strandi214 – 216Combined sources3
Beta strandi218 – 224Combined sources7
Turni241 – 243Combined sources3
Beta strandi244 – 248Combined sources5
Turni249 – 251Combined sources3
Beta strandi252 – 258Combined sources7
Helixi260 – 263Combined sources4
Helixi264 – 266Combined sources3
Helixi268 – 277Combined sources10
Helixi282 – 296Combined sources15
Beta strandi302 – 308Combined sources7
Beta strandi313 – 318Combined sources6
Beta strandi325 – 331Combined sources7
Turni333 – 335Combined sources3
Beta strandi339 – 344Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1APYX-ray2.00A/C24-185[»]
B/D206-346[»]
1APZX-ray2.30A/C24-185[»]
B/D206-346[»]
ProteinModelPortaliP20933.
SMRiP20933.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20933.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni234 – 237Substrate binding4
Regioni257 – 260Substrate binding4

Sequence similaritiesi

Belongs to the Ntn-hydrolase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1593. Eukaryota.
COG1446. LUCA.
GeneTreeiENSGT00530000063034.
HOVERGENiHBG004289.
InParanoidiP20933.
KOiK01444.
OMAiKFFGAVI.
OrthoDBiEOG091G0L36.
PhylomeDBiP20933.
TreeFamiTF300756.

Family and domain databases

InterProiIPR029055. Ntn_hydrolases_N.
IPR000246. Peptidase_T2.
[Graphical view]
PANTHERiPTHR10188. PTHR10188. 2 hits.
PfamiPF01112. Asparaginase_2. 1 hit.
[Graphical view]
SUPFAMiSSF56235. SSF56235. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P20933-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARKSNLPVL LVPFLLCQAL VRCSSPLPLV VNTWPFKNAT EAAWRALASG
60 70 80 90 100
GSALDAVESG CAMCEREQCD GSVGFGGSPD ELGETTLDAM IMDGTTMDVG
110 120 130 140 150
AVGDLRRIKN AIGVARKVLE HTTHTLLVGE SATTFAQSMG FINEDLSTTA
160 170 180 190 200
SQALHSDWLA RNCQPNYWRN VIPDPSKYCG PYKPPGILKQ DIPIHKETED
210 220 230 240 250
DRGHDTIGMV VIHKTGHIAA GTSTNGIKFK IHGRVGDSPI PGAGAYADDT
260 270 280 290 300
AGAAAATGNG DILMRFLPSY QAVEYMRRGE DPTIACQKVI SRIQKHFPEF
310 320 330 340
FGAVICANVT GSYGAACNKL STFTQFSFMV YNSEKNQPTE EKVDCI
Length:346
Mass (Da):37,208
Last modified:February 9, 2010 - v2
Checksum:i766F1690B5B62FFA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21V → A in AAB60655 (PubMed:1840528).Curated1
Sequence conflicti21V → A in CAA43958 (PubMed:1840528).Curated1
Sequence conflicti25S → C AA sequence (PubMed:2011603).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01542712V → L in AGU; uncertain pathological significance. 1 PublicationCorresponds to variant rs74626221dbSNPEnsembl.1
Natural variantiVAR_00506960G → D in AGU. Corresponds to variant rs121964907dbSNPEnsembl.1
Natural variantiVAR_00507072S → P in AGU; specifically prevents the proteolytic activation cleavage of AGA in the endoplasmic reticulum. 1 PublicationCorresponds to variant rs121964909dbSNPEnsembl.1
Natural variantiVAR_015428100G → E in AGU. 1 PublicationCorresponds to variant rs386833421dbSNPEnsembl.1
Natural variantiVAR_005071101A → V in AGU. Corresponds to variant rs121964908dbSNPEnsembl.1
Natural variantiVAR_015429135F → S in AGU. 1 PublicationCorresponds to variant rs386833427dbSNPEnsembl.1
Natural variantiVAR_033533149T → S.8 PublicationsCorresponds to variant rs2228119dbSNPEnsembl.1
Natural variantiVAR_005072161R → Q in AGU. 3 PublicationsCorresponds to variant rs192195150dbSNPEnsembl.1
Natural variantiVAR_005073163C → S in AGU; most frequent mutation; abolishes autocatalytic cleavage and enzyme activity. 3 PublicationsCorresponds to variant rs121964904dbSNPEnsembl.1
Natural variantiVAR_015430252G → E in AGU. 1 PublicationCorresponds to variant rs386833433dbSNPEnsembl.1
Natural variantiVAR_015431252G → R in AGU. 1 PublicationCorresponds to variant rs386833432dbSNPEnsembl.1
Natural variantiVAR_015432257T → I in AGU. 1 PublicationCorresponds to variant rs386833434dbSNPEnsembl.1
Natural variantiVAR_005074302G → R in AGU. Corresponds to variant rs121964905dbSNPEnsembl.1
Natural variantiVAR_005075306C → R in AGU. Corresponds to variant rs121964906dbSNPEnsembl.1
Natural variantiVAR_061026322T → I.Corresponds to variant rs56849061dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55762 mRNA. Translation: CAA39288.1.
X55330 mRNA. Translation: CAA39029.1.
U21281
, U21273, U21274, U21275, U21277, U21278, U21279, U21280 Genomic DNA. Translation: AAB60655.1.
X61959 Genomic DNA. Translation: CAA43958.1.
M64073 mRNA. Translation: AAA35903.1.
M64075 mRNA. Translation: AAA35904.1. Sequence problems.
M64076 mRNA. Translation: AAA35905.1. Sequence problems.
M60808 mRNA. Translation: AAA35901.1.
M60809 mRNA. Translation: AAA35902.1.
AK312982 mRNA. Translation: BAG35819.1.
CR541715 mRNA. Translation: CAG46516.1.
AC078881 Genomic DNA. Translation: AAY40915.1.
AC027627 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04714.1.
CH471056 Genomic DNA. Translation: EAX04715.1.
BC012392 mRNA. Translation: AAH12392.1.
CCDSiCCDS3829.1.
PIRiS11343. MUHUGD.
RefSeqiNP_000018.2. NM_000027.3.
NP_001165459.1. NM_001171988.1.
UniGeneiHs.207776.

Genome annotation databases

EnsembliENST00000264595; ENSP00000264595; ENSG00000038002.
GeneIDi175.
KEGGihsa:175.
UCSCiuc003iuu.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55762 mRNA. Translation: CAA39288.1.
X55330 mRNA. Translation: CAA39029.1.
U21281
, U21273, U21274, U21275, U21277, U21278, U21279, U21280 Genomic DNA. Translation: AAB60655.1.
X61959 Genomic DNA. Translation: CAA43958.1.
M64073 mRNA. Translation: AAA35903.1.
M64075 mRNA. Translation: AAA35904.1. Sequence problems.
M64076 mRNA. Translation: AAA35905.1. Sequence problems.
M60808 mRNA. Translation: AAA35901.1.
M60809 mRNA. Translation: AAA35902.1.
AK312982 mRNA. Translation: BAG35819.1.
CR541715 mRNA. Translation: CAG46516.1.
AC078881 Genomic DNA. Translation: AAY40915.1.
AC027627 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04714.1.
CH471056 Genomic DNA. Translation: EAX04715.1.
BC012392 mRNA. Translation: AAH12392.1.
CCDSiCCDS3829.1.
PIRiS11343. MUHUGD.
RefSeqiNP_000018.2. NM_000027.3.
NP_001165459.1. NM_001171988.1.
UniGeneiHs.207776.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1APYX-ray2.00A/C24-185[»]
B/D206-346[»]
1APZX-ray2.30A/C24-185[»]
B/D206-346[»]
ProteinModelPortaliP20933.
SMRiP20933.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106683. 8 interactors.
IntActiP20933. 2 interactors.
STRINGi9606.ENSP00000264595.

Chemistry databases

BindingDBiP20933.

Protein family/group databases

MEROPSiT02.001.

PTM databases

iPTMnetiP20933.
PhosphoSitePlusiP20933.

Polymorphism and mutation databases

BioMutaiAGA.
DMDMi288558804.

Proteomic databases

EPDiP20933.
MaxQBiP20933.
PaxDbiP20933.
PeptideAtlasiP20933.
PRIDEiP20933.

Protocols and materials databases

DNASUi175.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264595; ENSP00000264595; ENSG00000038002.
GeneIDi175.
KEGGihsa:175.
UCSCiuc003iuu.3. human.

Organism-specific databases

CTDi175.
DisGeNETi175.
GeneCardsiAGA.
H-InvDBHIX0004652.
HGNCiHGNC:318. AGA.
HPAiHPA031415.
HPA031417.
MalaCardsiAGA.
MIMi208400. phenotype.
613228. gene.
neXtProtiNX_P20933.
OpenTargetsiENSG00000038002.
Orphaneti93. Aspartylglucosaminuria.
PharmGKBiPA24615.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1593. Eukaryota.
COG1446. LUCA.
GeneTreeiENSGT00530000063034.
HOVERGENiHBG004289.
InParanoidiP20933.
KOiK01444.
OMAiKFFGAVI.
OrthoDBiEOG091G0L36.
PhylomeDBiP20933.
TreeFamiTF300756.

Enzyme and pathway databases

BioCyciMetaCyc:HS00528-MONOMER.
ZFISH:HS00528-MONOMER.
BRENDAi3.5.1.26. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SABIO-RKP20933.

Miscellaneous databases

ChiTaRSiAGA. human.
EvolutionaryTraceiP20933.
GeneWikiiAspartylglucosaminidase.
GenomeRNAii175.
PMAP-CutDBP20933.
PROiP20933.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000038002.
CleanExiHS_AGA.
ExpressionAtlasiP20933. baseline and differential.
GenevisibleiP20933. HS.

Family and domain databases

InterProiIPR029055. Ntn_hydrolases_N.
IPR000246. Peptidase_T2.
[Graphical view]
PANTHERiPTHR10188. PTHR10188. 2 hits.
PfamiPF01112. Asparaginase_2. 1 hit.
[Graphical view]
SUPFAMiSSF56235. SSF56235. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiASPG_HUMAN
AccessioniPrimary (citable) accession number: P20933
Secondary accession number(s): B2R7H2
, D3DP47, Q4W5Q2, Q6FHN6, Q9UCK6, Q9UCK7, Q9UCK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 9, 2010
Last modified: November 30, 2016
This is version 172 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

Keywords - Technical termi

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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.