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 02-SEP-2026, entry version 226. 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 AGU GLN-161 AND SER-163, VARIANT RP SER-149, 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 AGU GLN-161 AND SER-163, VARIANT SER-149, 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 VARIANTS AGU ASP-60; VAL-101; ARG-302 AND ARG-306. 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=N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H2O = N- CC acetyl-beta-D-glucosaminylamine + L-aspartate + H(+); 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:1301945, ECO:0000269|PubMed:1703489, CC ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2011603, CC ECO:0000269|PubMed:8776587, ECO:0000269|PubMed:9137882}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the Ntn-hydrolase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_000027.4. DR RefSeq; NP_001165459.1; NM_001171988.2. 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 AlphaFoldDB; P20933; -. DR SMR; P20933; -. DR BioGRID; 106683; 49. DR FunCoup; P20933; 486. DR IntAct; P20933; 20. DR STRING; 9606.ENSP00000264595; -. DR BindingDB; P20933; -. DR MEROPS; T02.001; -. DR GlyConnect; P20933; 3 N-Linked glycans (1 site). DR GlyCosmos; P20933; 2 sites, 3 glycans. DR GlyGen; P20933; 4 sites, 9 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; P20933; -. DR MetOSite; P20933; -. DR PhosphoSitePlus; P20933; -. DR BioMuta; AGA; -. DR DMDM; 288558804; -. DR jPOST; P20933; -. DR MassIVE; P20933; -. DR PaxDb; 9606-ENSP00000264595; -. DR PeptideAtlas; P20933; -. DR ProteomicsDB; 53827; -. DR Pumba; P20933; -. DR Antibodypedia; 28679; 156 antibodies from 22 providers. DR DNASU; 175; -. DR Ensembl; ENST00000264595.7; ENSP00000264595.2; ENSG00000038002.10. 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 AGR; HGNC:318; -. DR ClinPGx; PA24615; -. DR CTD; 175; -. DR DisGeNET; 175; -. DR GeneCards; AGA; -. DR GeneReviews; AGA; -. DR HGNC; HGNC:318; AGA. DR HPA; ENSG00000038002; Low tissue specificity. DR MalaCards; AGA; -. DR MIM; 208400; phenotype. DR MIM; 613228; gene. DR OpenTargets; ENSG00000038002; -. DR Orphanet; 93; Aspartylglucosaminuria. DR VEuPathDB; HostDB:ENSG00000038002; -. DR eggNOG; KOG1593; Eukaryota. DR GeneTree; ENSGT00950000183045; -. DR HOGENOM; CLU_021603_0_0_1; -. DR InParanoid; P20933; -. DR OMA; YKPIINI; -. DR OrthoDB; 188713at2759; -. DR PAN-GO; P20933; 3 GO annotations based on evolutionary models. DR PhylomeDB; P20933; -. DR BioCyc; MetaCyc:HS00528-MONOMER; -. 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 Agora; ENSG00000038002; -. DR BioGRID-ORCS; 175; 12 hits in 1161 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 199 other cell types or tissues. DR ExpressionAtlas; P20933; baseline and differential. 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; 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:0006517; P:protein deglycosylation; IDA:UniProtKB. DR CDD; cd04513; Glycosylasparaginase; 1. DR FunFam; 3.60.20.30:FF:000003; N(4)-(Beta-N-acetylglucosaminyl)-L-asparaginase isoform X1; 1. DR Gene3D; 3.60.20.30; (Glycosyl)asparaginase; 1. DR InterPro; IPR029055; Ntn_hydrolases_N. DR InterPro; IPR000246; Peptidase_T2. DR PANTHER; PTHR10188; L-ASPARAGINASE; 1. DR PANTHER; PTHR10188:SF6; N(4)-(BETA-N-ACETYLGLUCOSAMINYL)-L-ASPARAGINASE; 1. DR Pfam; PF01112; Asparaginase_2; 1. DR SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1. DR PDBsum; 1APY; -. DR PDBsum; 1APZ; -. PE 1: Evidence at protein level; KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Lysosome; KW Protease; Proteomics identification; 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 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 /evidence="ECO:0000269|PubMed:1301945" 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 /evidence="ECO:0000269|PubMed:1301945" 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 /evidence="ECO:0000269|PubMed:1301945" FT /id="VAR_005074" FT VARIANT 306 FT /note="C -> R (in AGU; dbSNP:rs121964906)" FT /evidence="ECO:0000269|PubMed:1301945" 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 141..143 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 242..244 FT /evidence="ECO:0007829|PDB:1APY" FT STRAND 245..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..317 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 //