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P20933 (ASPG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
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
Gene names
Name:AGA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H2O = N-acetyl-beta-D-glucosaminylamine + L-aspartate. Ref.3 Ref.5

Subunit structure

Heterotetramer of two alpha and two beta chains arranged as a dimer of alpha/beta heterodimers. Ref.14

Subcellular location

Lysosome.

Post-translational modification

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.

Involvement in disease

Aspartylglucosaminuria (AGU) [MIM:208400]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.5 Ref.6 Ref.16 Ref.17 Ref.18

Sequence similarities

Belongs to the Ntn-hydrolase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.6
Chain24 – 205182Glycosylasparaginase alpha chain
PRO_0000002333
Chain206 – 346141Glycosylasparaginase beta chain
PRO_0000002334

Regions

Region234 – 2374Substrate binding
Region257 – 2604Substrate binding

Sites

Active site2061Nucleophile Ref.14

Amino acid modifications

Modified residue241Blocked amino end (Ser)
Glycosylation381N-linked (GlcNAc...) Ref.1 Ref.12 Ref.14
Glycosylation3081N-linked (GlcNAc...) Ref.14
Disulfide bond64 ↔ 69 Ref.14
Disulfide bond163 ↔ 179 Ref.14
Disulfide bond286 ↔ 306 Ref.14
Disulfide bond317 ↔ 345 Ref.14

Natural variations

Natural variant121V → L in AGU; uncertain pathological significance. Ref.18
Corresponds to variant rs74626221 [ dbSNP | Ensembl ].
VAR_015427
Natural variant601G → D in AGU.
VAR_005069
Natural variant721S → P in AGU; specifically prevents the proteolytic activation cleavage of AGA in the endoplasmic reticulum. Ref.16
VAR_005070
Natural variant1001G → E in AGU. Ref.17
VAR_015428
Natural variant1011A → V in AGU.
VAR_005071
Natural variant1351F → S in AGU. Ref.17
VAR_015429
Natural variant1491T → S. Ref.1 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.10 Ref.11
Corresponds to variant rs2228119 [ dbSNP | Ensembl ].
VAR_033533
Natural variant1611R → Q in AGU. Ref.3 Ref.5 Ref.6
Corresponds to variant rs192195150 [ dbSNP | Ensembl ].
VAR_005072
Natural variant1631C → S in AGU; most frequent mutation; abolishes autocatalytic cleavage and enzyme activity. Ref.3 Ref.5 Ref.6
Corresponds to variant rs121964904 [ dbSNP | Ensembl ].
VAR_005073
Natural variant2521G → E in AGU. Ref.18
VAR_015430
Natural variant2521G → R in AGU. Ref.18
VAR_015431
Natural variant2571T → I in AGU. Ref.18
VAR_015432
Natural variant3021G → R in AGU.
VAR_005074
Natural variant3061C → R in AGU.
VAR_005075
Natural variant3221T → I.
Corresponds to variant rs56849061 [ dbSNP | Ensembl ].
VAR_061026

Experimental info

Sequence conflict211V → A in AAB60655. Ref.4
Sequence conflict211V → A in CAA43958. Ref.4
Sequence conflict251S → C AA sequence Ref.6

Secondary structure

...................................................... 346
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P20933 [UniParc].

Last modified February 9, 2010. Version 2.
Checksum: 766F1690B5B62FFA

FASTA34637,208
        10         20         30         40         50         60 
MARKSNLPVL LVPFLLCQAL VRCSSPLPLV VNTWPFKNAT EAAWRALASG GSALDAVESG 

        70         80         90        100        110        120 
CAMCEREQCD GSVGFGGSPD ELGETTLDAM IMDGTTMDVG AVGDLRRIKN AIGVARKVLE 

       130        140        150        160        170        180 
HTTHTLLVGE SATTFAQSMG FINEDLSTTA SQALHSDWLA RNCQPNYWRN VIPDPSKYCG 

       190        200        210        220        230        240 
PYKPPGILKQ DIPIHKETED DRGHDTIGMV VIHKTGHIAA GTSTNGIKFK IHGRVGDSPI 

       250        260        270        280        290        300 
PGAGAYADDT AGAAAATGNG DILMRFLPSY QAVEYMRRGE DPTIACQKVI SRIQKHFPEF 

       310        320        330        340 
FGAVICANVT GSYGAACNKL STFTQFSFMV YNSEKNQPTE EKVDCI 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of a cDNA for human glycosylasparaginase. A single gene encodes the subunits of this lysosomal amidase."
Fisher K.J., Tollersrud O.-K., Aronson N.N. Jr.
FEBS Lett. 269:440-444(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-149.
[2]Erratum
Fisher K.J., Tollersrud O.-K., Aronson N.N. Jr.
FEBS Lett. 276:232-232(1990) [PubMed] [Europe PMC] [Abstract]
[3]"Aspartylglucosaminuria: cDNA encoding human aspartylglucosaminidase and the missense mutation causing the disease."
Ikonen E., Baumann M., Groen K., Syvaenen A.-C., Enomaa N., Halila R., Aula P., Peltonen L.
EMBO J. 10:51-58(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 206-235, ACTIVATION BY CLEAVAGE, CATALYTIC ACTIVITY, VARIANTS SER-149; AGU GLN-161 AND SER-163, CHARACTERIZATION OF VARIANT AGU SER-163.
Tissue: Fetal liver.
[4]"Genomic structure of human lysosomal glycosylasparaginase."
Park H., Fisher K.J., Aronson N.N. Jr.
FEBS Lett. 288:168-172(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-149.
[5]"Characterization of the mutation responsible for aspartylglucosaminuria in three Finnish patients. Amino acid substitution Cys163-->Ser abolishes the activity of lysosomal glycosylasparaginase and its conversion into subunits."
Fisher K.J., Aronson N.N. Jr.
J. Biol. Chem. 266:12105-12113(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOCATALYTIC CLEAVAGE, CATALYTIC ACTIVITY, VARIANTS SER-149; AGU GLN-161 AND SER-163.
[6]"Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase."
Mononen I., Heisterkamp N., Kaartinen V., Williams J.C., Yates J.R. III, Griffin P.R., Hood L.E., Groffen J.
Proc. Natl. Acad. Sci. U.S.A. 88:2941-2945(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-45; 47-60; 67-84; 98-120; 123-190; 206-314 AND 320-343, VARIANTS AGU GLN-161 AND SER-163.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-149.
Tissue: Urinary bladder.
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-149.
[9]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-149.
[11]"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], VARIANT SER-149.
Tissue: Ovary.
[12]"Purification and structure of human liver aspartylglucosaminidase."
Rip J.W., Coulter-Mackie M.B., Rupar C.A., Gordon B.A.
Biochem. J. 288:1005-1010(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-44 AND 206-231, GLYCOSYLATION AT ASN-38.
Tissue: Liver.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Three-dimensional structure of human lysosomal aspartylglucosaminidase."
Oinonen C., Tikkanen R., Rouvinen J., Peltonen L.
Nat. Struct. Biol. 2:1102-1108(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-185 IN COMPLEX WITH ASPARTIC ACID, SUBUNIT, ACTIVE SITE, GLYCOSYLATION AT ASN-38 AND ASN-308, DISULFIDE BONDS.
[15]"Mutations causing aspartylglucosaminuria (AGU): a lysosomal accumulation disease."
Ikonen E., Peltonen L.
Hum. Mutat. 1:361-365(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON AGU VARIANTS.
[16]"Ser72-->Pro active-site disease mutation in human lysosomal aspartylglucosaminidase: abnormal intracellular processing and evidence for extracellular activation."
Peltola M., Tikkanen R., Peltonen L., Jalanko A.
Hum. Mol. Genet. 5:737-743(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AGU PRO-72.
[17]"Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation."
Laitinen A., Hietala M., Haworth J.C., Schroeder M.L., Seargeant L.E., Greenberg C.R., Aula P.
Clin. Genet. 51:174-178(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AGU GLU-100 AND SER-135.
[18]"Molecular pathogenesis of a disease: structural consequences of aspartylglucosaminuria mutations."
Saarela J., Laine M., Oinonen C., Schantz C., Jalanko A., Rouvinen J., Peltonen L.
Hum. Mol. Genet. 10:983-995(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AGU LEU-12; ARG-252; GLU-252 AND ILE-257.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X55762 mRNA. Translation: CAA39288.1.
X55330 mRNA. Translation: CAA39029.1.
U21281 expand/collapse EMBL AC list , 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.
CCDSCCDS3829.1.
PIRMUHUGD. S11343.
RefSeqNP_000018.2. NM_000027.3.
NP_001165459.1. NM_001171988.1.
UniGeneHs.207776.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1APYX-ray2.00A/C24-185[»]
B/D206-346[»]
1APZX-ray2.30A/C24-185[»]
B/D206-346[»]
ProteinModelPortalP20933.
SMRP20933. Positions 25-185, 206-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106683. 3 interactions.
IntActP20933. 2 interactions.
STRING9606.ENSP00000264595.

Chemistry

BindingDBP20933.

Protein family/group databases

MEROPST02.001.

PTM databases

PhosphoSiteP20933.

Polymorphism databases

DMDM288558804.

Proteomic databases

MaxQBP20933.
PaxDbP20933.
PRIDEP20933.

Protocols and materials databases

DNASU175.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264595; ENSP00000264595; ENSG00000038002.
GeneID175.
KEGGhsa:175.
UCSCuc003iuu.2. human.

Organism-specific databases

CTD175.
GeneCardsGC04M178351.
H-InvDBHIX0004652.
HGNCHGNC:318. AGA.
HPAHPA031415.
HPA031417.
MIM208400. phenotype.
613228. gene.
neXtProtNX_P20933.
Orphanet93. Aspartylglucosaminuria.
PharmGKBPA24615.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1446.
HOVERGENHBG004289.
InParanoidP20933.
KOK01444.
OMAKFFGAVI.
OrthoDBEOG7RV9GJ.
PhylomeDBP20933.
TreeFamTF300756.

Enzyme and pathway databases

BRENDA3.5.1.26. 2681.
SABIO-RKP20933.

Gene expression databases

ArrayExpressP20933.
BgeeP20933.
CleanExHS_AGA.
GenevestigatorP20933.

Family and domain databases

InterProIPR029055. Ntn_hydrolases_N.
IPR000246. Peptidase_T2.
[Graphical view]
PANTHERPTHR10188. PTHR10188. 1 hit.
PfamPF01112. Asparaginase_2. 1 hit.
[Graphical view]
SUPFAMSSF56235. SSF56235. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAGA. human.
EvolutionaryTraceP20933.
GeneWikiAspartylglucosaminidase.
GenomeRNAi175.
NextBio702.
PMAP-CutDBP20933.
PROP20933.
SOURCESearch...

Entry information

Entry nameASPG_HUMAN
AccessionPrimary (citable) accession number: P20933
Secondary accession number(s): B2R7H2 expand/collapse secondary AC list , D3DP47, Q4W5Q2, Q6FHN6, Q9UCK6, Q9UCK7, Q9UCK8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 9, 2010
Last modified: July 9, 2014
This is version 151 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 4

Human chromosome 4: entries, gene names and cross-references to MIM