OGA_RAT
ID OGA_RAT Reviewed; 916 AA.
AC Q8VIJ5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Protein O-GlcNAcase {ECO:0000303|PubMed:8034696, ECO:0000303|Ref.1, ECO:0000305};
DE Short=OGA;
DE EC=3.2.1.169 {ECO:0000269|PubMed:8034696};
DE AltName: Full=Beta-N-acetylhexosaminidase;
DE AltName: Full=Beta-hexosaminidase;
DE AltName: Full=Bifunctional protein NCOAT {ECO:0000303|PubMed:15485860};
DE AltName: Full=Meningioma-expressed antigen 5;
DE AltName: Full=N-acetyl-beta-D-glucosaminidase;
DE AltName: Full=N-acetyl-beta-glucosaminidase;
GN Name=Oga {ECO:0000312|RGD:621077}; Synonyms=Hexc, Mea5, Mgea5;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Fischer 344;
RA Liu K., Paterson A.J., Van Tine B.A., Konrad R.J., Parlow A.F., Jimi S.,
RA Chin E. Jr., Kudlow J.E.;
RT "The O-GlcNAcase gene is a candidate for diabetes susceptibility in GK
RT rats.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RX PubMed=8034696; DOI=10.1016/s0021-9258(17)32170-1;
RA Dong D.-L., Hart G.W.;
RT "Purification and characterization of an O-GlcNAc selective N-acetyl-beta-
RT D-glucosaminidase from rat spleen cytosol.";
RL J. Biol. Chem. 269:19321-19330(1994).
RN [3]
RP IDENTIFICATION OF ISOFORMS 2 AND 3.
RC STRAIN=GK, and Sprague-Dawley;
RX PubMed=15485860; DOI=10.1074/jbc.m410406200;
RA Toleman C., Paterson A.J., Whisenhunt T.R., Kudlow J.E.;
RT "Characterization of the histone acetyltransferase (HAT) domain of a
RT bifunctional protein with activable O-GlcNAcase and HAT activities.";
RL J. Biol. Chem. 279:53665-53673(2004).
RN [4]
RP FUNCTION OF ISOFORMS 2 AND 3, AND LACK OF CATALYTIC ACTIVITY OF ISOFORMS 2
RP AND 3.
RX PubMed=16517082; DOI=10.1016/j.bbagen.2006.01.017;
RA Toleman C., Paterson A.J., Kudlow J.E.;
RT "Location and characterization of the O-GlcNAcase active site.";
RL Biochim. Biophys. Acta 1760:829-839(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: [Isoform 1]: Cleaves GlcNAc but not GalNAc from O-
CC glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-
CC methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-
CC GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:8034696). Does
CC not bind acetyl-CoA and does not have histone acetyltransferase
CC activity. {ECO:0000250|UniProtKB:O60502, ECO:0000269|PubMed:8034696}.
CC -!- FUNCTION: [Isoform 2]: Lacks enzyme activity.
CC {ECO:0000269|PubMed:16517082}.
CC -!- FUNCTION: [Isoform 3]: Lacks enzyme activity.
CC {ECO:0000269|PubMed:16517082}.
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:8034696};
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:8034696};
CC -!- ACTIVITY REGULATION: Inhibited by Cu(2+), Hg(2+), Cd(2+) and Zn(2+) at
CC 1 mM. Not inhibited by Co(2+), Mg(2+), Ca(2+), Mn(2+), Fe(3+) and EDTA.
CC Also inhibited by sodium chloride at 1M and 2-amino-2-hydroxymethyl-
CC 1,3-propanediol (trishydroxymethylaminomethane) at 75 mM.
CC {ECO:0000269|PubMed:8034696}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.55 mM for pNP-O-GlcNAc {ECO:0000269|PubMed:8034696};
CC pH dependence:
CC Optimum pH is 6.4. Activity decreases sharply at pH below 5.0.
CC {ECO:0000269|PubMed:8034696};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. Less active at room
CC temperature and shows very little activity at 4 degrees Celsius.
CC Loses activity at 57 degrees Celsius within 5 minutes.
CC {ECO:0000269|PubMed:8034696};
CC -!- SUBUNIT: Monomer. Interacts with CLOCK (By similarity).
CC {ECO:0000250|UniProtKB:O60502, ECO:0000250|UniProtKB:Q9EQQ9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8034696}. Cytoplasm
CC {ECO:0000269|PubMed:8034696}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8VIJ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VIJ5-2; Sequence=VSP_020873;
CC Name=3;
CC IsoId=Q8VIJ5-3; Sequence=VSP_020874;
CC -!- TISSUE SPECIFICITY: Detected in spleen (at protein level). Ubiquitous.
CC Expressed at highest levels in the brain and spleen.
CC {ECO:0000269|PubMed:8034696}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis. The
CC fragments interact with each other; cleavage does not decrease enzyme
CC activity. {ECO:0000250|UniProtKB:O60502}.
CC -!- MISCELLANEOUS: [Isoform 2]: Lack hexosaminidase activity.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Lack hexosaminidase activity.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 84 family. {ECO:0000305}.
CC -!- CAUTION: Was initially identified as a bi-functional protein that has
CC an N-terminal domain with O-GlcNAcase activity and a C-terminal domain
CC that has histone acetyltransferase activity (PubMed:15485860). The
CC protein has apparent histone acetyltransferase activity when expressed
CC in mammalian cells, but not when expressed in bacterial cells
CC (PubMed:15485860), suggesting that the histone acetyltransferase
CC activity might be due to the presence of a contaminant.
CC Characterization of the human ortholog shows that this protein does not
CC bind acetyl-CoA and therefore cannot have acetyltransferase activity.
CC {ECO:0000305}.
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DR EMBL; AY039679; AAK72103.1; -; mRNA.
DR RefSeq; NP_571979.1; NM_131904.1. [Q8VIJ5-1]
DR AlphaFoldDB; Q8VIJ5; -.
DR SMR; Q8VIJ5; -.
DR STRING; 10116.ENSRNOP00000059568; -.
DR BindingDB; Q8VIJ5; -.
DR ChEMBL; CHEMBL3351213; -.
DR GuidetoPHARMACOLOGY; 3101; -.
DR CAZy; GH84; Glycoside Hydrolase Family 84.
DR iPTMnet; Q8VIJ5; -.
DR PhosphoSitePlus; Q8VIJ5; -.
DR jPOST; Q8VIJ5; -.
DR PaxDb; Q8VIJ5; -.
DR PRIDE; Q8VIJ5; -.
DR GeneID; 154968; -.
DR KEGG; rno:154968; -.
DR UCSC; RGD:621077; rat. [Q8VIJ5-1]
DR CTD; 10724; -.
DR RGD; 621077; Oga.
DR eggNOG; KOG3698; Eukaryota.
DR HOGENOM; CLU_009837_1_0_1; -.
DR InParanoid; Q8VIJ5; -.
DR PhylomeDB; Q8VIJ5; -.
DR PRO; PR:Q8VIJ5; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q8VIJ5; RN.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
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:RGD.
DR GO; GO:0004402; F:histone acetyltransferase activity; IMP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0046060; P:dATP metabolic process; IMP:RGD.
DR GO; GO:0009100; P:glycoprotein metabolic process; IBA:GO_Central.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IMP:RGD.
DR GO; GO:0070265; P:necrotic cell death; IMP:RGD.
DR GO; GO:0010616; P:negative regulation of cardiac muscle adaptation; IMP:RGD.
DR GO; GO:0060051; P:negative regulation of protein glycosylation; IMP:RGD.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:RGD.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IMP:RGD.
DR GO; GO:0031343; P:positive regulation of cell killing; IMP:RGD.
DR GO; GO:0051054; P:positive regulation of DNA metabolic process; IMP:RGD.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:RGD.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; IMP:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IMP:RGD.
DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IMP:RGD.
DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:RGD.
DR GO; GO:0006517; P:protein deglycosylation; ISO:RGD.
DR GO; GO:0006612; P:protein targeting to membrane; IMP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR011496; Beta-N-acetylglucosaminidase.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF07555; NAGidase; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Glycosidase; Hydrolase; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..916
FT /note="Protein O-GlcNAcase"
FT /id="PRO_0000252120"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 440..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..480
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O60502"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q2CEE3"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q0TR53"
FT BINDING 174
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q0TR53"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q2CEE3"
FT BINDING 278..280
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q2CEE3"
FT BINDING 285
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q2CEE3"
FT BINDING 313
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q2CEE3"
FT SITE 413..414
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250|UniProtKB:O60502"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 250..398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_020873"
FT VAR_SEQ 250..345
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_020874"
SQ SEQUENCE 916 AA; 102918 MW; 4BA1746F0AF2E380 CRC64;
MVQKESQAAL EERESERNAN PASVSGASLE PSAAPAPGED NPSGAGAAAG TGAAGGARRF
LCGVVEGFYG RPWVMEQRKE LFRRLQKWEL NTYLYAPKDD YKHRMFWREM YSVEEAEQLM
TLISAAREYE IEFIYAISPG LDITFSNPKE VSTLKRKLDQ VSQFGCRSFA LLFDDIDHNM
CAADKEVFSS FAHAQVSITN EIYQYLGEPE TFLFCPTEYC GTFCYPSVSQ SPYLRTVGEK
LLPGIEVLWT GPKVVSKEIP VESIEEVSKI IKRAPVIWDN IHANDYDQKR LFLGPYKGRS
TELIPRLKGV LTNPNCEFEA NYVAIHTLAT WYKSNMNGVR KDVVMTDSED STVSIQIKLE
NEGSDEDIET DVLYSPQMAL KLALTEWLQE FGVPHQYSSR QVAHSGAKTS VVDGTPLVAA
PSLNATTVVT TVYQEPIMSQ GAALSGEPSA LTKEEEKKQP DEEPMDMVVE KQEESEHKSD
NQILTEIVEA KMAEELKPMD TDKESIAESK SPEMSMQEDC INDIAPMQTD EQANKEQFVP
GPNEKPLYAA EPVTLEDLQL LADLFYLPYE HGPKGAQMLR EFQWLRANSS VVSVNCKGKD
SEKIEEWRSR AAKFEEMCAL 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
