ID OGA_HUMAN Reviewed; 916 AA. AC O60502; B7WPB9; D3DR79; E9PGF9; O75166; Q86WV0; Q8IV98; Q9BVA5; Q9HAR0; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 2. DT 27-MAR-2024, entry version 183. DE RecName: Full=Protein O-GlcNAcase {ECO:0000303|PubMed:11148210, ECO:0000303|PubMed:11788610, ECO:0000305}; DE Short=OGA {ECO:0000303|PubMed:20863279}; DE EC=3.2.1.169 {ECO:0000269|PubMed:11148210, ECO:0000269|PubMed:11788610, ECO:0000269|PubMed:18586680, ECO:0000269|PubMed:20863279, ECO:0000269|PubMed:22365600, ECO:0000269|PubMed:28939839, ECO:0000305|PubMed:20673219}; DE AltName: Full=Beta-N-acetylglucosaminidase {ECO:0000303|PubMed:11148210}; DE AltName: Full=Beta-N-acetylhexosaminidase; DE AltName: Full=Beta-hexosaminidase; DE AltName: Full=Meningioma-expressed antigen 5 {ECO:0000303|PubMed:9811929}; DE AltName: Full=N-acetyl-beta-D-glucosaminidase; DE AltName: Full=N-acetyl-beta-glucosaminidase; DE AltName: Full=Nuclear cytoplasmic O-GlcNAcase and acetyltransferase; DE Short=NCOAT; GN Name=OGA {ECO:0000303|PubMed:20863279, ECO:0000312|HGNC:HGNC:7056}; GN Synonyms=HEXC, KIAA0679 {ECO:0000303|PubMed:9734811}, MEA5, MGEA5 GN {ECO:0000303|PubMed:11341771}; 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] (ISOFORMS 1 AND 3). RC TISSUE=Meningioma; RX PubMed=9811929; DOI=10.1093/hmg/7.12.1859; RA Heckel D., Comtesse N., Brass N., Blin N., Zang K.D., Meese E.; RT "Novel immunogenic antigen homologous to hyaluronidase in meningioma."; RL Hum. Mol. Genet. 7:1859-1872(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=11341771; DOI=10.1006/bbrc.2001.4815; RA Comtesse N., Maldener E., Meese E.; RT "Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase RT and a beta-N-acetylglucosaminidase."; RL Biochem. Biophys. Res. Commun. 283:634-640(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, RP ACTIVITY REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain; RX PubMed=11148210; DOI=10.1074/jbc.m010420200; RA Gao Y., Wells L., Comer F.I., Parker G.J., Hart G.W.; RT "Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and RT characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from RT human brain."; RL J. Biol. Chem. 276:9838-9845(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [5] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-602. RC TISSUE=Cervix, Eye, and Skin; 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 [9] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, PTM, RP AND SUBCELLULAR LOCATION. RX PubMed=11788610; DOI=10.1074/jbc.m109656200; RA Wells L., Gao Y., Mahoney J.A., Vosseller K., Chen C., Rosen A., Hart G.W.; RT "Dynamic O-glycosylation of nuclear and cytosolic proteins: further RT characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O- RT GlcNAcase."; RL J. Biol. Chem. 277:1755-1761(2002). RN [10] RP ACTIVE SITE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-174 AND ASP-175. RX PubMed=16533067; DOI=10.1021/bi052370b; RA Cetinbas N., Macauley M.S., Stubbs K.A., Drapala R., Vocadlo D.J.; RT "Identification of Asp174 and Asp175 as the key catalytic residues of human RT O-GlcNAcase by functional analysis of site-directed mutants."; RL Biochemistry 45:3835-3844(2006). RN [11] RP PTM, SITE, MUTAGENESIS OF ASP-413, AND CATALYTIC ACTIVITY. RX PubMed=18586680; DOI=10.1074/jbc.m804116200; RA Butkinaree C., Cheung W.D., Park S., Park K., Barber M., Hart G.W.; RT "Characterization of beta-N-acetylglucosaminidase cleavage by caspase-3 RT during apoptosis."; RL J. Biol. Chem. 283:23557-23566(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-69; ASP-175; VAL-255; RP TYR-286; ASP-287 AND TRP-679. RX PubMed=20863279; DOI=10.1042/bj20101338; RA Schimpl M., Schuttelkopf A.W., Borodkin V.S., van Aalten D.M.; RT "Human OGA binds substrates in a conserved peptide recognition groove."; RL Biochem. J. 432:1-7(2010). RN [16] RP FUNCTION OF ISOFORMS 1 AND 3, AND CATALYTIC ACTIVITY. RX PubMed=20673219; DOI=10.1134/s0006297910070175; RA Li J., Huang C.L., Zhang L.W., Lin L., Li Z.H., Zhang F.W., Wang P.; RT "Isoforms of human O-GlcNAcase show distinct catalytic efficiencies."; RL Biochemistry (Mosc.) 75:938-943(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [22] RP LACK OF ACETYLTRANSFERASE ACTIVITY, AND FUNCTION. RX PubMed=24088714; DOI=10.1098/rsob.130021; RA Rao F.V., Schuttelkopf A.W., Dorfmueller H.C., Ferenbach A.T., RA Navratilova I., van Aalten D.M.; RT "Structure of a bacterial putative acetyltransferase defines the fold of RT the human O-GlcNAcase C-terminal domain."; RL Open Biol. 3:130021-130021(2013). RN [23] RP INTERACTION WITH HUMAN T-CELL LEUKEMIA VIRUS 1/HTLV-1 PROTEIN TAX. RX PubMed=28742148; DOI=10.1371/journal.ppat.1006518; RA Groussaud D., Khair M., Tollenaere A.I., Waast L., Kuo M.S., Mangeney M., RA Martella C., Fardini Y., Coste S., Souidi M., Benit L., Pique C., Issad T.; RT "Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein RT facilitates viral transcription."; RL PLoS Pathog. 13:E1006518-E1006518(2017). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 402-408, MUTAGENESIS OF TYR-69, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22365600; DOI=10.1016/j.chembiol.2012.01.011; RA Schimpl M., Borodkin V.S., Gray L.J., van Aalten D.M.; RT "Synergy of peptide and sugar in O-GlcNAcase substrate recognition."; RL Chem. Biol. 19:173-178(2012). RN [25] {ECO:0007744|PDB:5VVO, ECO:0007744|PDB:5VVT, ECO:0007744|PDB:5VVU, ECO:0007744|PDB:5VVV, ECO:0007744|PDB:5VVX} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 60-400 AND 553-704 IN COMPLEX RP WITH PEPTIDE SUBSTRATES, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28939839; DOI=10.1038/s41467-017-00865-1; RA Li B., Li H., Hu C.W., Jiang J.; RT "Structural insights into the substrate binding adaptability and RT specificity of human O-GlcNAcase."; RL Nat. Commun. 8:666-666(2017). CC -!- FUNCTION: [Isoform 1]: Cleaves GlcNAc but not GalNAc from O- CC glycosylated proteins (PubMed:11148210, PubMed:11788610, CC PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839). CC Deglycosylates a large and diverse number of proteins, such as CRYAB, CC ELK1, LMNB1 and TAB1 (PubMed:28939839). Can use p-nitrophenyl-beta- CC GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p- CC nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) CC (PubMed:20673219). Does not bind acetyl-CoA and does not have histone CC acetyltransferase activity (PubMed:24088714). CC {ECO:0000269|PubMed:11148210, ECO:0000269|PubMed:11788610, CC ECO:0000269|PubMed:20673219, ECO:0000269|PubMed:22365600, CC ECO:0000269|PubMed:24088714, ECO:0000269|PubMed:28939839}. CC -!- FUNCTION: [Isoform 3]: Cleaves GlcNAc but not GalNAc from O- CC glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate CC but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in CC vitro), but has about six times lower specific activity than isoform 1. CC {ECO:0000269|PubMed:20673219}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-(N-acetyl-beta-D-glucosaminyl)-L-seryl-[protein] + H2O = CC L-seryl-[protein] + N-acetyl-D-glucosamine; Xref=Rhea:RHEA:48876, CC Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:12251, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:90838, ChEBI:CHEBI:506227; CC EC=3.2.1.169; Evidence={ECO:0000269|PubMed:11148210, CC ECO:0000269|PubMed:11788610, ECO:0000269|PubMed:18586680, CC ECO:0000269|PubMed:20863279, ECO:0000269|PubMed:22365600, CC ECO:0000269|PubMed:28939839, ECO:0000305|PubMed:20673219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-(N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + H2O CC = L-threonyl-[protein] + N-acetyl-D-glucosamine; CC Xref=Rhea:RHEA:48892, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:12252, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:90840, CC ChEBI:CHEBI:506227; EC=3.2.1.169; CC Evidence={ECO:0000269|PubMed:11148210, ECO:0000269|PubMed:11788610, CC ECO:0000269|PubMed:18586680, ECO:0000269|PubMed:20863279, CC ECO:0000269|PubMed:22365600, ECO:0000269|PubMed:28939839, CC ECO:0000305|PubMed:20673219}; CC -!- ACTIVITY REGULATION: Inhibited by N-acetylglucosamine and not N- CC acetylgalactosamine. {ECO:0000269|PubMed:11148210}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.1 mM for pNP-GlcNAc {ECO:0000269|PubMed:11788610}; CC Vmax=652 umol/min/mg enzyme with pNP-GLcNAc as substrate CC {ECO:0000269|PubMed:11788610}; CC pH dependence: CC Optimum pH is 5.7-7. {ECO:0000269|PubMed:11148210}; CC -!- SUBUNIT: Monomer (PubMed:11788610). Interacts with CLOCK (By CC similarity). {ECO:0000250|UniProtKB:Q9EQQ9, CC ECO:0000269|PubMed:11788610}. CC -!- SUBUNIT: (Microbial infection) Interacts with human T-cell leukemia CC virus 1/HTLV-1 protein Tax; this interaction increases Tax interacting CC partner CREB1 O-GlcNAcylation. {ECO:0000269|PubMed:28742148}. CC -!- INTERACTION: CC O60502; O60502: OGA; NbExp=3; IntAct=EBI-715814, EBI-715814; CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus CC {ECO:0000269|PubMed:11341771}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:11148210, ECO:0000269|PubMed:11341771, CC ECO:0000269|PubMed:11788610}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O60502-1; Sequence=Displayed; CC Name=2; CC IsoId=O60502-2; Sequence=VSP_020866, VSP_020869; CC Name=3; Synonyms=MGEA5s; CC IsoId=O60502-3; Sequence=VSP_020867, VSP_020868; CC Name=4; CC IsoId=O60502-4; Sequence=VSP_020866; CC -!- TISSUE SPECIFICITY: Ubiquitous. Shows highest expression in the brain, CC placenta and pancreas. {ECO:0000269|PubMed:11148210, CC ECO:0000269|PubMed:11341771}. CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis. The CC fragments interact with each other; cleavage does not decrease enzyme CC activity. {ECO:0000269|PubMed:11788610, ECO:0000269|PubMed:18586680}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 84 family. CC {ECO:0000255|PROSITE-ProRule:PRU01353, ECO:0000305}. CC -!- CAUTION: The mouse and rat orthologs were initially identified as bi- CC functional proteins containing an N-terminal domain with O-GlcNAcase CC activity and a C-terminal domain with histone acetyltransferase CC activity. The histone acetyltransferase activity was detected only when CC the protein was expressed in mammalian cells, but not when expressed in CC bacterial cells, suggesting that the histone acetyltransferase activity CC might be due to the presence of a contaminant. Comparison of the human CC protein with a bacterial putative acetyltransferase (AC Q2CEE2) shows CC that the residues important for acetyl-CoA binding are not conserved, CC and that the residues proposed to be important for histone CC acetyltransferase activity are not in a position where they could CC participate in catalysis. Characterization of the human protein shows CC that it does not bind acetyl-CoA and therefore cannot have CC acetyltransferase activity. {ECO:0000269|PubMed:24088714, CC ECO:0000305|PubMed:24088714}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH47877.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAA31654.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AF036144; AAD05385.2; -; mRNA. DR EMBL; AF307332; AAG21428.1; -; mRNA. DR EMBL; AB014579; BAA31654.2; ALT_INIT; mRNA. DR EMBL; AC010789; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49744.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49741.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49742.1; -; Genomic_DNA. DR EMBL; BC001343; AAH01343.1; -; mRNA. DR EMBL; BC039583; AAH39583.2; -; mRNA. DR EMBL; BC047877; AAH47877.1; ALT_SEQ; mRNA. DR CCDS; CCDS44471.1; -. [O60502-4] DR CCDS; CCDS7520.1; -. [O60502-1] DR PIR; T00360; T00360. DR RefSeq; NP_001135906.1; NM_001142434.1. [O60502-4] DR RefSeq; NP_036347.1; NM_012215.3. [O60502-1] DR PDB; 2YDQ; X-ray; 2.60 A; T=402-408. DR PDB; 5M7R; X-ray; 2.35 A; A/B=1-916. DR PDB; 5M7S; X-ray; 2.40 A; A/B=1-916. DR PDB; 5M7T; X-ray; 2.60 A; A/B=1-916. DR PDB; 5M7U; X-ray; 2.30 A; A/B=1-916. DR PDB; 5TKE; X-ray; 2.48 A; A/B=60-400, A/B=553-704. DR PDB; 5UHK; X-ray; 2.97 A; A/C=56-400, B/D=544-705. DR PDB; 5UHL; X-ray; 3.14 A; A/C=56-400, B/D=544-705. DR PDB; 5UHO; X-ray; 3.21 A; A/C=56-400, B/D=544-705. DR PDB; 5UHP; X-ray; 2.79 A; A/B/C/D=14-400, E/F/G/H=554-705. DR PDB; 5UN8; X-ray; 2.13 A; A/B/C/D=60-400, A/B/C/D=553-704. DR PDB; 5UN9; X-ray; 2.50 A; A/B=60-400, A/B=553-704. DR PDB; 5VVO; X-ray; 2.60 A; A/B=60-400, A/B=553-704. DR PDB; 5VVT; X-ray; 2.80 A; A/C=60-400, A/C=553-704. DR PDB; 5VVU; X-ray; 2.70 A; A/C=60-400, A/C=553-704. DR PDB; 5VVV; X-ray; 2.80 A; A/C=60-400, A/C=553-704. DR PDB; 5VVX; X-ray; 2.90 A; A/C=60-400, A/C=553-704. DR PDB; 6HKI; X-ray; 3.30 A; A/B=1-916. DR PDB; 6PM9; X-ray; 2.86 A; A/B/C/D=14-400, E/F/G/H=553-705. DR PDB; 7OU6; X-ray; 2.41 A; AAA/BBB=1-916. DR PDB; 7YEH; EM; 3.92 A; C/D=1-916. DR PDB; 8P0L; X-ray; 2.50 A; A/B=1-916. DR PDBsum; 2YDQ; -. DR PDBsum; 5M7R; -. DR PDBsum; 5M7S; -. DR PDBsum; 5M7T; -. DR PDBsum; 5M7U; -. DR PDBsum; 5TKE; -. DR PDBsum; 5UHK; -. DR PDBsum; 5UHL; -. DR PDBsum; 5UHO; -. DR PDBsum; 5UHP; -. DR PDBsum; 5UN8; -. DR PDBsum; 5UN9; -. DR PDBsum; 5VVO; -. DR PDBsum; 5VVT; -. DR PDBsum; 5VVU; -. DR PDBsum; 5VVV; -. DR PDBsum; 5VVX; -. DR PDBsum; 6HKI; -. DR PDBsum; 6PM9; -. DR PDBsum; 7OU6; -. DR PDBsum; 7YEH; -. DR PDBsum; 8P0L; -. DR AlphaFoldDB; O60502; -. DR EMDB; EMD-33773; -. DR SMR; O60502; -. DR BioGRID; 115948; 127. DR IntAct; O60502; 38. DR MINT; O60502; -. DR STRING; 9606.ENSP00000354850; -. DR BindingDB; O60502; -. DR ChEMBL; CHEMBL5921; -. DR DrugBank; DB00428; Streptozocin. DR GuidetoPHARMACOLOGY; 3101; -. DR CAZy; GH84; Glycoside Hydrolase Family 84. DR GlyCosmos; O60502; 5 sites, 2 glycans. DR GlyGen; O60502; 6 sites, 3 O-linked glycans (6 sites). DR iPTMnet; O60502; -. DR MetOSite; O60502; -. DR PhosphoSitePlus; O60502; -. DR SwissPalm; O60502; -. DR BioMuta; MGEA5; -. DR CPTAC; CPTAC-1223; -. DR EPD; O60502; -. DR jPOST; O60502; -. DR MassIVE; O60502; -. DR MaxQB; O60502; -. DR PaxDb; 9606-ENSP00000354850; -. DR PeptideAtlas; O60502; -. DR ProteomicsDB; 20314; -. DR ProteomicsDB; 49438; -. [O60502-1] DR ProteomicsDB; 49439; -. [O60502-2] DR ProteomicsDB; 49440; -. [O60502-3] DR Pumba; O60502; -. DR Antibodypedia; 31340; 217 antibodies from 28 providers. DR DNASU; 10724; -. DR Ensembl; ENST00000357797.9; ENSP00000350445.4; ENSG00000198408.14. [O60502-2] DR Ensembl; ENST00000361464.8; ENSP00000354850.3; ENSG00000198408.14. [O60502-1] DR Ensembl; ENST00000370094.7; ENSP00000359112.3; ENSG00000198408.14. [O60502-3] DR Ensembl; ENST00000439817.5; ENSP00000409973.1; ENSG00000198408.14. [O60502-4] DR GeneID; 10724; -. DR KEGG; hsa:10724; -. DR MANE-Select; ENST00000361464.8; ENSP00000354850.3; NM_012215.5; NP_036347.1. DR UCSC; uc001ktv.3; human. [O60502-1] DR AGR; HGNC:7056; -. DR CTD; 10724; -. DR DisGeNET; 10724; -. DR GeneCards; OGA; -. DR HGNC; HGNC:7056; OGA. DR HPA; ENSG00000198408; Low tissue specificity. DR MIM; 604039; gene. DR neXtProt; NX_O60502; -. DR OpenTargets; ENSG00000198408; -. DR PharmGKB; PA30787; -. DR VEuPathDB; HostDB:ENSG00000198408; -. DR eggNOG; KOG3698; Eukaryota. DR GeneTree; ENSGT00390000007726; -. DR HOGENOM; CLU_009837_1_0_1; -. DR InParanoid; O60502; -. DR OMA; ICTRTYL; -. DR OrthoDB; 2903353at2759; -. DR PhylomeDB; O60502; -. DR TreeFam; TF313732; -. DR BioCyc; MetaCyc:HS03036-MONOMER; -. DR BRENDA; 3.2.1.169; 2681. DR BRENDA; 3.2.1.35; 2681. DR PathwayCommons; O60502; -. DR SignaLink; O60502; -. DR SIGNOR; O60502; -. DR BioGRID-ORCS; 10724; 120 hits in 1179 CRISPR screens. DR ChiTaRS; MGEA5; human. DR GeneWiki; MGEA5; -. DR GenomeRNAi; 10724; -. DR Pharos; O60502; Tchem. DR PRO; PR:O60502; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O60502; Protein. DR Bgee; ENSG00000198408; Expressed in sperm and 205 other cell types or tissues. DR ExpressionAtlas; O60502; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0102167; F:[protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine O-N-acetyl-alpha-D-glucosaminase activity; IEA:UniProtKB-EC. DR GO; GO:0102571; F:[protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity; IEA:UniProtKB-EC. DR GO; GO:0102166; F:[protein]-3-O-(N-acetyl-D-glucosaminyl)-L-threonine O-N-acetyl-alpha-D-glucosaminase activity; IEA:UniProtKB-EC. DR GO; GO:0016231; F:beta-N-acetylglucosaminidase activity; IDA:UniProtKB. DR GO; GO:0004415; F:hyalurononglucosaminidase activity; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0006516; P:glycoprotein catabolic process; TAS:ProtInc. DR GO; GO:0009100; P:glycoprotein metabolic process; IBA:GO_Central. DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:UniProtKB. DR GO; GO:0006517; P:protein deglycosylation; IDA:UniProtKB. DR GO; GO:0006493; P:protein O-linked glycosylation; NAS:ParkinsonsUK-UCL. DR DisProt; DP02479; -. DR Gene3D; 3.40.630.30; -; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR IDEAL; IID00643; -. DR InterPro; IPR016181; Acyl_CoA_acyltransferase. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR InterPro; IPR011496; O-GlcNAcase_cat. DR PANTHER; PTHR13170; O-GLCNACASE; 1. DR PANTHER; PTHR13170:SF16; PROTEIN O-GLCNACASE; 1. DR Pfam; PF07555; NAGidase; 1. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1. DR PROSITE; PS52009; GH84; 1. DR Genevisible; O60502; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Glycosidase; KW Host-virus interaction; Hydrolase; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1..916 FT /note="Protein O-GlcNAcase" FT /id="PRO_0000252118" FT DOMAIN 60..336 FT /note="GH84" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01353" FT REGION 1..48 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 441..465 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 450..465 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 175 FT /note="Proton donor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01353, FT ECO:0000305|PubMed:16533067" FT BINDING 67 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 98 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 174 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 175 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 219 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 285 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT BINDING 313 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /evidence="ECO:0000269|PubMed:28939839, FT ECO:0007744|PDB:5VVT" FT SITE 413..414 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000269|PubMed:18586680" FT MOD_RES 364 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT VAR_SEQ 346..398 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_020866" FT VAR_SEQ 663..677 FT /note="CRSHSSAQFLIGDQE -> RCTRNNLFSSNILSL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9811929" FT /id="VSP_020867" FT VAR_SEQ 678..916 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9811929" FT /id="VSP_020868" FT VAR_SEQ 691..704 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_020869" FT VARIANT 46 FT /note="G -> E (in dbSNP:rs3740421)" FT /id="VAR_027761" FT VARIANT 602 FT /note="E -> K (in dbSNP:rs17853930)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027762" FT MUTAGEN 69 FT /note="Y->K,Q: Strongly reduces affinity for glycopeptide FT substrates. Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279, FT ECO:0000269|PubMed:22365600" FT MUTAGEN 69 FT /note="Y->S: Strongly reduces affinity for glycopeptide FT substrates. Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279, FT ECO:0000269|PubMed:22365600" FT MUTAGEN 174 FT /note="D->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:16533067" FT MUTAGEN 175 FT /note="D->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:16533067" FT MUTAGEN 175 FT /note="D->N: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279" FT MUTAGEN 255 FT /note="V->G,T: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279" FT MUTAGEN 286 FT /note="Y->S: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279" FT MUTAGEN 287 FT /note="D->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279" FT MUTAGEN 413 FT /note="D->A: Abrogates cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:18586680" FT MUTAGEN 679 FT /note="W->N: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:20863279" FT TURN 50..52 FT /evidence="ECO:0007829|PDB:6PM9" FT TURN 54..57 FT /evidence="ECO:0007829|PDB:5UHP" FT STRAND 61..66 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 75..87 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 104..108 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 113..128 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 140..142 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 148..162 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 163..165 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 168..172 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 182..187 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:5VVU" FT HELIX 191..205 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 228..230 FT /evidence="ECO:0007829|PDB:5M7R" FT HELIX 232..240 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 245..249 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 252..255 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 261..271 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 276..279 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 285..287 FT /evidence="ECO:0007829|PDB:5UHK" FT HELIX 301..306 FT /evidence="ECO:0007829|PDB:5UN8" FT STRAND 308..312 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 318..321 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 322..332 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 334..337 FT /evidence="ECO:0007829|PDB:5UHL" FT HELIX 376..388 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 389..391 FT /evidence="ECO:0007829|PDB:5M7R" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:5M7T" FT HELIX 555..564 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 573..587 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 589..591 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 601..603 FT /evidence="ECO:0007829|PDB:6HKI" FT HELIX 605..628 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 634..661 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 662..666 FT /evidence="ECO:0007829|PDB:5M7R" FT TURN 680..683 FT /evidence="ECO:0007829|PDB:5UN8" FT HELIX 684..692 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 694..699 FT /evidence="ECO:0007829|PDB:5UN8" FT TURN 710..712 FT /evidence="ECO:0007829|PDB:5M7R" SQ SEQUENCE 916 AA; 102915 MW; 01F8A64A9B1475C6 CRC64; MVQKESQATL EERESELSSN PAASAGASLE PPAAPAPGED NPAGAGGAAV AGAAGGARRF LCGVVEGFYG RPWVMEQRKE LFRRLQKWEL NTYLYAPKDD YKHRMFWREM YSVEEAEQLM TLISAAREYE IEFIYAISPG LDITFSNPKE VSTLKRKLDQ VSQFGCRSFA LLFDDIDHNM CAADKEVFSS FAHAQVSITN EIYQYLGEPE TFLFCPTEYC GTFCYPNVSQ SPYLRTVGEK LLPGIEVLWT GPKVVSKEIP VESIEEVSKI IKRAPVIWDN IHANDYDQKR LFLGPYKGRS TELIPRLKGV LTNPNCEFEA NYVAIHTLAT WYKSNMNGVR KDVVMTDSED STVSIQIKLE NEGSDEDIET DVLYSPQMAL KLALTEWLQE FGVPHQYSSR QVAHSGAKAS VVDGTPLVAA PSLNATTVVT TVYQEPIMSQ GAALSGEPTT LTKEEEKKQP DEEPMDMVVE KQEETDHKND NQILSEIVEA KMAEELKPMD TDKESIAESK SPEMSMQEDC ISDIAPMQTD EQTNKEQFVP GPNEKPLYTA EPVTLEDLQL LADLFYLPYE HGPKGAQMLR EFQWLRANSS VVSVNCKGKD SEKIEEWRSR AAKFEEMCGL VMGMFTRLSN CANRTILYDM YSYVWDIKSI MSMVKSFVQW LGCRSHSSAQ FLIGDQEPWA FRGGLAGEFQ RLLPIDGAND LFFQPPPLTP TSKVYTIRPY FPKDEASVYK ICREMYDDGV GLPFQSQPDL IGDKLVGGLL SLSLDYCFVL EDEDGICGYA LGTVDVTPFI KKCKISWIPF MQEKYTKPNG DKELSEAEKI MLSFHEEQEV LPETFLANFP SLIKMDIHKK VTDPSVAKSM MACLLSSLKA NGSRGAFCEV RPDDKRILEF YSKLGCFEIA KMEGFPKDVV ILGRSL //