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MGP003563

UniProt Annotations

Entry Information
Gene NameO-linked N-acetylglucosamine (GlcNAc) transferase
Protein EntryOGT1_HUMAN
UniProt IDO15294
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=3; Synonyms=Nucleocytoplasmic isoform, ncOGT; IsoId=O15294-1; Sequence=Displayed; Name=2; Synonyms=Mitochondrial isoform, mOGT; IsoId=O15294-2; Sequence=VSP_006553; Name=1; IsoId=O15294-3; Sequence=VSP_014164; Name=4; Synonyms=Short isoform, sOGT; IsoId=O15294-4; Sequence=VSP_040764; Note=No experimental confirmation available.;
Biophysicochemical PropertiesKinetic parameters: KM=1.8 uM for UDP-N-acetyl-D-glucosamine {ECO:0000269|PubMed:21240259};
Catalytic ActivityUDP-N-acetyl-D-glucosamine + [protein]-L- serine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine.
Catalytic ActivityUDP-N-acetyl-D-glucosamine + [protein]-L- threonine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L- threonine.
DiseaseNote=Regulation of OGT activity and altered O- GlcNAcylations are implicated in diabetes and Alzheimer disease. O-GlcNAcylation of AKT1 affects insulin signaling and, possibly diabetes. Reduced O-GlcNAcylations and resulting increased phosphorylations of MAPT/TAU are observed in Alzheimer disease (AD) brain cerebrum.
DomainThe TPR repeat domain is required for substrate binding and oligomerization. {ECO:0000269|PubMed:15361863}.
Enzyme RegulationSubject to product inhibition by UDP. {ECO:0000269|PubMed:21240259}.
FunctionCatalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta- linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling. Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3) (PubMed:22121020, PubMed:23353889). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins ARNTL/BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, PubMed:18288188, PubMed:19377461, PubMed:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863). {ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:19377461, ECO:0000269|PubMed:19451179, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20018868, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:22121020, ECO:0000269|PubMed:22923583, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24474760}.
FunctionIsoform 2: the mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.
InductionInduction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux. {ECO:0000269|PubMed:19073609}.
InteractionP51610:HCFC1; NbExp=9; IntAct=EBI-539828, EBI-396176; P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-539828, EBI-3957603; O95644:NFATC1; NbExp=2; IntAct=EBI-539828, EBI-6907210; Q04206:RELA; NbExp=2; IntAct=EBI-539828, EBI-73886; Q6N021:TET2; NbExp=7; IntAct=EBI-539828, EBI-310727; O43151:TET3; NbExp=4; IntAct=EBI-539828, EBI-2831148; Q8BG87:Tet3 (xeno); NbExp=2; IntAct=EBI-539828, EBI-9031997;
PathwayProtein modification; protein glycosylation.
PtmPhosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity. {ECO:0000250}.
PtmUbiquitinated, leading to its proteasomal degradation. {ECO:0000269|PubMed:21285374}.
SimilarityBelongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily. {ECO:0000305}.
SimilarityContains 13 TPR repeats. {ECO:0000255|PROSITE- ProRule:PRU00339}.
Subcellular LocationIsoform 2: Mitochondrion. Membrane. Note=Associates with the mitochondrial inner membrane.
Subcellular LocationIsoform 3: Cytoplasm. Nucleus. Cell membrane. Note=Mostly in the nucleus. Retained in the nucleus via interaction with HCFC1. After insulin induction, translocated from the nucleus to the cell membrane via phophatidylinisotide binding. Colocalizes with AKT1 at the plasma membrane.
Subcellular LocationIsoform 4: Cytoplasm. Nucleus.
SubunitHeterotrimer; consists of one 78 kDa subunit and two 110 kDa subunits dimerized via TPR repeats 6 and 7. Interacts (via TPR repeats 6 and 7) with ATXN10 (By similarity). Component of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38, PPP1CA, PPP1CB, HCFC1, PPP1CC and ACTB. Component of a THAP1/THAP3-HCFC1- OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O- glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase. Interacts (via TPR 5-6) with TET1, TET2 and TET3. Interacts with ARNTL/BMAL1 (By similarity). {ECO:0000250}.
Tissue SpecificityHighly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver. {ECO:0000269|PubMed:9083068}.
Web ResourceName=Functional Glycomics Gateway - GTase; Note=UDP- N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110kDa subunit; URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_554";
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