ASPG_HUMAN
ID ASPG_HUMAN Reviewed; 346 AA.
AC P20933; B2R7H2; D3DP47; Q4W5Q2; Q6FHN6; Q9UCK6; Q9UCK7; Q9UCK8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase;
DE EC=3.5.1.26 {ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2401370};
DE AltName: Full=Aspartylglucosaminidase;
DE AltName: Full=Glycosylasparaginase;
DE AltName: Full=N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase;
DE Contains:
DE RecName: Full=Glycosylasparaginase alpha chain;
DE Contains:
DE RecName: Full=Glycosylasparaginase beta chain;
DE Flags: Precursor;
GN Name=AGA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, VARIANT SER-149,
RP AND GLYCOSYLATION.
RX PubMed=2401370; DOI=10.1016/0014-5793(90)81211-6;
RA Fisher K.J., Tollersrud O.-K., Aronson N.N. Jr.;
RT "Cloning and sequence analysis of a cDNA for human glycosylasparaginase. A
RT single gene encodes the subunits of this lysosomal amidase.";
RL FEBS Lett. 269:440-444(1990).
RN [2]
RP ERRATUM OF PUBMED:2401370.
RX PubMed=2265705; DOI=10.1016/0014-5793(90)80551-s;
RA Fisher K.J., Tollersrud O.-K., Aronson N.N. Jr.;
RL FEBS Lett. 276:232-232(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 206-235, ACTIVATION BY
RP CLEAVAGE, CATALYTIC ACTIVITY, VARIANTS SER-149; AGU GLN-161 AND SER-163,
RP CHARACTERIZATION OF VARIANT AGU SER-163, AND FUNCTION.
RC TISSUE=Fetal liver;
RX PubMed=1703489; DOI=10.1002/j.1460-2075.1991.tb07920.x;
RA Ikonen E., Baumann M., Groen K., Syvaenen A.-C., Enomaa N., Halila R.,
RA Aula P., Peltonen L.;
RT "Aspartylglucosaminuria: cDNA encoding human aspartylglucosaminidase and
RT the missense mutation causing the disease.";
RL EMBO J. 10:51-58(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-149.
RX PubMed=1840528; DOI=10.1016/0014-5793(91)81027-6;
RA Park H., Fisher K.J., Aronson N.N. Jr.;
RT "Genomic structure of human lysosomal glycosylasparaginase.";
RL FEBS Lett. 288:168-172(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AUTOCATALYTIC CLEAVAGE, CATALYTIC ACTIVITY,
RP VARIANTS SER-149; AGU GLN-161 AND SER-163, AND FUNCTION.
RX PubMed=1904874; DOI=10.1016/s0021-9258(18)99071-x;
RA Fisher K.J., Aronson N.N. Jr.;
RT "Characterization of the mutation responsible for aspartylglucosaminuria in
RT three Finnish patients. Amino acid substitution Cys163-->Ser abolishes the
RT activity of lysosomal glycosylasparaginase and its conversion into
RT subunits.";
RL J. Biol. Chem. 266:12105-12113(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-45; 47-60; 67-84;
RP 98-120; 123-190; 206-314 AND 320-343, AND VARIANTS AGU GLN-161 AND SER-163.
RX PubMed=2011603; DOI=10.1073/pnas.88.7.2941;
RA Mononen I., Heisterkamp N., Kaartinen V., Williams J.C., Yates J.R. III,
RA Griffin P.R., Hood L.E., Groffen J.;
RT "Aspartylglycosaminuria in the Finnish population: identification of two
RT point mutations in the heavy chain of glycoasparaginase.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2941-2945(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-149.
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-149.
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-149.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-149.
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP PROTEIN SEQUENCE OF 25-44 AND 206-231, AND GLYCOSYLATION AT ASN-38.
RC TISSUE=Liver;
RX PubMed=1281977; DOI=10.1042/bj2881005;
RA Rip J.W., Coulter-Mackie M.B., Rupar C.A., Gordon B.A.;
RT "Purification and structure of human liver aspartylglucosaminidase.";
RL Biochem. J. 288:1005-1010(1992).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER CYS-23, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-185 IN COMPLEX WITH ASPARTIC
RP ACID, SUBUNIT, ACTIVE SITE, GLYCOSYLATION AT ASN-38 AND ASN-308, AND
RP DISULFIDE BONDS.
RX PubMed=8846222; DOI=10.1038/nsb1295-1102;
RA Oinonen C., Tikkanen R., Rouvinen J., Peltonen L.;
RT "Three-dimensional structure of human lysosomal aspartylglucosaminidase.";
RL Nat. Struct. Biol. 2:1102-1108(1995).
RN [17]
RP REVIEW ON AGU VARIANTS.
RX PubMed=1301945; DOI=10.1002/humu.1380010503;
RA Ikonen E., Peltonen L.;
RT "Mutations causing aspartylglucosaminuria (AGU): a lysosomal accumulation
RT disease.";
RL Hum. Mutat. 1:361-365(1992).
RN [18]
RP VARIANT AGU PRO-72.
RX PubMed=8776587; DOI=10.1093/hmg/5.6.737;
RA Peltola M., Tikkanen R., Peltonen L., Jalanko A.;
RT "Ser72-->Pro active-site disease mutation in human lysosomal
RT aspartylglucosaminidase: abnormal intracellular processing and evidence for
RT extracellular activation.";
RL Hum. Mol. Genet. 5:737-743(1996).
RN [19]
RP VARIANTS AGU GLU-100 AND SER-135.
RX PubMed=9137882; DOI=10.1111/j.1399-0004.1997.tb02448.x;
RA Laitinen A., Hietala M., Haworth J.C., Schroeder M.L., Seargeant L.E.,
RA Greenberg C.R., Aula P.;
RT "Two novel mutations in a Canadian family with aspartylglucosaminuria and
RT early outcome post bone marrow transplantation.";
RL Clin. Genet. 51:174-178(1997).
RN [20]
RP VARIANTS AGU LEU-12; ARG-252; GLU-252 AND ILE-257.
RX PubMed=11309371; DOI=10.1093/hmg/10.9.983;
RA Saarela J., Laine M., Oinonen C., Schantz C., Jalanko A., Rouvinen J.,
RA Peltonen L.;
RT "Molecular pathogenesis of a disease: structural consequences of
RT aspartylglucosaminuria mutations.";
RL Hum. Mol. Genet. 10:983-995(2001).
CC -!- FUNCTION: Cleaves the GlcNAc-Asn bond which joins oligosaccharides to
CC the peptide of asparagine-linked glycoproteins.
CC {ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874,
CC ECO:0000269|PubMed:2401370}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine = H(+)
CC + L-aspartate + N-acetyl-beta-D-glucosaminylamine;
CC Xref=Rhea:RHEA:11544, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15947, ChEBI:CHEBI:29991, ChEBI:CHEBI:58080; EC=3.5.1.26;
CC Evidence={ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874,
CC ECO:0000269|PubMed:2401370};
CC -!- SUBUNIT: Heterotetramer of two alpha and two beta chains arranged as a
CC dimer of alpha/beta heterodimers. {ECO:0000269|PubMed:8846222}.
CC -!- INTERACTION:
CC P20933; O60333-2: KIF1B; NbExp=3; IntAct=EBI-1223922, EBI-10975473;
CC P20933; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-1223922, EBI-11749135;
CC P20933; P07196: NEFL; NbExp=3; IntAct=EBI-1223922, EBI-475646;
CC P20933; O76024: WFS1; NbExp=3; IntAct=EBI-1223922, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- PTM: Cleaved into an alpha and beta chain by autocatalysis; this
CC activates the enzyme. The N-terminal residue of the beta subunit is
CC responsible for the nucleophile hydrolase activity.
CC {ECO:0000269|PubMed:1281977, ECO:0000269|PubMed:1703489,
CC ECO:0000269|PubMed:1904874}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:2401370}.
CC -!- DISEASE: Aspartylglucosaminuria (AGU) [MIM:208400]: An inborn lysosomal
CC storage disease causing excess accumulation of glycoasparagine in the
CC body tissues and its increased excretion in urine. Clinical features
CC include mild to severe intellectual disability manifesting from the age
CC of two, coarse facial features and mild connective tissue
CC abnormalities. {ECO:0000269|PubMed:11309371,
CC ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874,
CC ECO:0000269|PubMed:2011603, ECO:0000269|PubMed:8776587,
CC ECO:0000269|PubMed:9137882}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Ntn-hydrolase family. {ECO:0000305}.
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DR EMBL; X55762; CAA39288.1; -; mRNA.
DR EMBL; X55330; CAA39029.1; -; mRNA.
DR EMBL; U21281; AAB60655.1; -; Genomic_DNA.
DR EMBL; U21273; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21274; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21275; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21277; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21278; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21279; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; U21280; AAB60655.1; JOINED; Genomic_DNA.
DR EMBL; X61959; CAA43958.1; -; Genomic_DNA.
DR EMBL; M64073; AAA35903.1; -; mRNA.
DR EMBL; M64075; AAA35904.1; ALT_SEQ; mRNA.
DR EMBL; M64076; AAA35905.1; ALT_SEQ; mRNA.
DR EMBL; M60808; AAA35901.1; -; mRNA.
DR EMBL; M60809; AAA35902.1; -; mRNA.
DR EMBL; AK312982; BAG35819.1; -; mRNA.
DR EMBL; CR541715; CAG46516.1; -; mRNA.
DR EMBL; AC078881; AAY40915.1; -; Genomic_DNA.
DR EMBL; AC027627; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04714.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04715.1; -; Genomic_DNA.
DR EMBL; BC012392; AAH12392.1; -; mRNA.
DR CCDS; CCDS3829.1; -.
DR PIR; S11343; MUHUGD.
DR RefSeq; NP_000018.2; NM_000027.3.
DR RefSeq; NP_001165459.1; NM_001171988.1.
DR PDB; 1APY; X-ray; 2.00 A; A/C=24-185, B/D=206-346.
DR PDB; 1APZ; X-ray; 2.30 A; A/C=24-185, B/D=206-346.
DR PDBsum; 1APY; -.
DR PDBsum; 1APZ; -.
DR AlphaFoldDB; P20933; -.
DR SMR; P20933; -.
DR BioGRID; 106683; 39.
DR IntAct; P20933; 11.
DR STRING; 9606.ENSP00000264595; -.
DR BindingDB; P20933; -.
DR MEROPS; T02.001; -.
DR GlyConnect; 1530; 3 N-Linked glycans (1 site).
DR GlyGen; P20933; 2 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P20933; -.
DR MetOSite; P20933; -.
DR PhosphoSitePlus; P20933; -.
DR BioMuta; AGA; -.
DR DMDM; 288558804; -.
DR EPD; P20933; -.
DR jPOST; P20933; -.
DR MassIVE; P20933; -.
DR MaxQB; P20933; -.
DR PaxDb; P20933; -.
DR PeptideAtlas; P20933; -.
DR PRIDE; P20933; -.
DR ProteomicsDB; 53827; -.
DR Antibodypedia; 28679; 163 antibodies from 22 providers.
DR DNASU; 175; -.
DR Ensembl; ENST00000264595.7; ENSP00000264595.2; ENSG00000038002.9.
DR GeneID; 175; -.
DR KEGG; hsa:175; -.
DR MANE-Select; ENST00000264595.7; ENSP00000264595.2; NM_000027.4; NP_000018.2.
DR UCSC; uc003iuu.3; human.
DR CTD; 175; -.
DR DisGeNET; 175; -.
DR GeneCards; AGA; -.
DR HGNC; HGNC:318; AGA.
DR HPA; ENSG00000038002; Low tissue specificity.
DR MalaCards; AGA; -.
DR MIM; 208400; phenotype.
DR MIM; 613228; gene.
DR neXtProt; NX_P20933; -.
DR OpenTargets; ENSG00000038002; -.
DR Orphanet; 93; Aspartylglucosaminuria.
DR PharmGKB; PA24615; -.
DR VEuPathDB; HostDB:ENSG00000038002; -.
DR eggNOG; KOG1593; Eukaryota.
DR GeneTree; ENSGT00950000183045; -.
DR HOGENOM; CLU_021603_0_0_1; -.
DR InParanoid; P20933; -.
DR OMA; PDENCET; -.
DR OrthoDB; 1487354at2759; -.
DR PhylomeDB; P20933; -.
DR TreeFam; TF300756; -.
DR BioCyc; MetaCyc:HS00528-MON; -.
DR BRENDA; 3.5.1.26; 2681.
DR PathwayCommons; P20933; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; P20933; -.
DR SignaLink; P20933; -.
DR BioGRID-ORCS; 175; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; AGA; human.
DR EvolutionaryTrace; P20933; -.
DR GeneWiki; Aspartylglucosaminidase; -.
DR GenomeRNAi; 175; -.
DR Pharos; P20933; Tbio.
DR PRO; PR:P20933; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P20933; protein.
DR Bgee; ENSG00000038002; Expressed in esophagus squamous epithelium and 198 other tissues.
DR ExpressionAtlas; P20933; baseline and differential.
DR Genevisible; P20933; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0003948; F:N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006517; P:protein deglycosylation; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR000246; Peptidase_T2.
DR PANTHER; PTHR10188; PTHR10188; 1.
DR Pfam; PF01112; Asparaginase_2; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Lysosome;
KW Protease; Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:2011603,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 24..205
FT /note="Glycosylasparaginase alpha chain"
FT /id="PRO_0000002333"
FT CHAIN 206..346
FT /note="Glycosylasparaginase beta chain"
FT /id="PRO_0000002334"
FT ACT_SITE 206
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:8846222"
FT BINDING 234..237
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8846222"
FT BINDING 257..260
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8846222"
FT MOD_RES 24
FT /note="Blocked amino end (Ser)"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1281977,
FT ECO:0000269|PubMed:2401370, ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT DISULFID 64..69
FT /evidence="ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT DISULFID 163..179
FT /evidence="ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT DISULFID 286..306
FT /evidence="ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT DISULFID 317..345
FT /evidence="ECO:0000269|PubMed:8846222,
FT ECO:0007744|PDB:1APY, ECO:0007744|PDB:1APZ"
FT VARIANT 12
FT /note="V -> L (in AGU; uncertain pathological significance;
FT dbSNP:rs74626221)"
FT /evidence="ECO:0000269|PubMed:11309371"
FT /id="VAR_015427"
FT VARIANT 60
FT /note="G -> D (in AGU; dbSNP:rs121964907)"
FT /id="VAR_005069"
FT VARIANT 72
FT /note="S -> P (in AGU; specifically prevents the
FT proteolytic activation cleavage of AGA in the endoplasmic
FT reticulum; dbSNP:rs121964909)"
FT /evidence="ECO:0000269|PubMed:8776587"
FT /id="VAR_005070"
FT VARIANT 100
FT /note="G -> E (in AGU; dbSNP:rs386833421)"
FT /evidence="ECO:0000269|PubMed:9137882"
FT /id="VAR_015428"
FT VARIANT 101
FT /note="A -> V (in AGU; dbSNP:rs121964908)"
FT /id="VAR_005071"
FT VARIANT 135
FT /note="F -> S (in AGU; dbSNP:rs386833427)"
FT /evidence="ECO:0000269|PubMed:9137882"
FT /id="VAR_015429"
FT VARIANT 149
FT /note="T -> S (in dbSNP:rs2228119)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1703489,
FT ECO:0000269|PubMed:1840528, ECO:0000269|PubMed:1904874,
FT ECO:0000269|PubMed:2401370, ECO:0000269|Ref.10,
FT ECO:0000269|Ref.8"
FT /id="VAR_033533"
FT VARIANT 161
FT /note="R -> Q (in AGU; dbSNP:rs192195150)"
FT /evidence="ECO:0000269|PubMed:1703489,
FT ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2011603"
FT /id="VAR_005072"
FT VARIANT 163
FT /note="C -> S (in AGU; most frequent mutation; abolishes
FT autocatalytic cleavage and enzyme activity;
FT dbSNP:rs121964904)"
FT /evidence="ECO:0000269|PubMed:1703489,
FT ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2011603"
FT /id="VAR_005073"
FT VARIANT 252
FT /note="G -> E (in AGU; dbSNP:rs386833433)"
FT /evidence="ECO:0000269|PubMed:11309371"
FT /id="VAR_015430"
FT VARIANT 252
FT /note="G -> R (in AGU; dbSNP:rs386833432)"
FT /evidence="ECO:0000269|PubMed:11309371"
FT /id="VAR_015431"
FT VARIANT 257
FT /note="T -> I (in AGU; dbSNP:rs386833434)"
FT /evidence="ECO:0000269|PubMed:11309371"
FT /id="VAR_015432"
FT VARIANT 302
FT /note="G -> R (in AGU; dbSNP:rs121964905)"
FT /id="VAR_005074"
FT VARIANT 306
FT /note="C -> R (in AGU; dbSNP:rs121964906)"
FT /id="VAR_005075"
FT VARIANT 322
FT /note="T -> I (in dbSNP:rs56849061)"
FT /id="VAR_061026"
FT CONFLICT 21
FT /note="V -> A (in Ref. 4; AAB60655/CAA43958)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="S -> C (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 37..48
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 53..67
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:1APY"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1APZ"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 129..138
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 149..160
FT /evidence="ECO:0007829|PDB:1APY"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1APZ"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:1APY"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 244..248
FT /evidence="ECO:0007829|PDB:1APY"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 268..277
FT /evidence="ECO:0007829|PDB:1APY"
FT HELIX 282..296
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1APY"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:1APY"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:1APZ"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:1APY"
SQ SEQUENCE 346 AA; 37208 MW; 766F1690B5B62FFA CRC64;
MARKSNLPVL LVPFLLCQAL VRCSSPLPLV VNTWPFKNAT EAAWRALASG GSALDAVESG
CAMCEREQCD GSVGFGGSPD ELGETTLDAM IMDGTTMDVG AVGDLRRIKN AIGVARKVLE
HTTHTLLVGE SATTFAQSMG FINEDLSTTA SQALHSDWLA RNCQPNYWRN VIPDPSKYCG
PYKPPGILKQ DIPIHKETED DRGHDTIGMV VIHKTGHIAA GTSTNGIKFK IHGRVGDSPI
PGAGAYADDT AGAAAATGNG DILMRFLPSY QAVEYMRRGE DPTIACQKVI SRIQKHFPEF
FGAVICANVT GSYGAACNKL STFTQFSFMV YNSEKNQPTE EKVDCI
