ID:OGT1_HUMAN DESCRIPTION: RecName: Full=UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit; EC=2.4.1.255; AltName: Full=O-GlcNAc transferase subunit p110; AltName: Full=O-linked N-acetylglucosamine transferase 110 kDa subunit; Short=OGT; FUNCTION: Catalyzes 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, PFKL, 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. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. FUNCTION: Isoform 2, the mitochondrial isoform (mOGT), is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + [protein]-L- serine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine. CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + [protein]-L- threonine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L- threonine. ENZYME REGULATION: Subject to product inhibition by UDP. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.8 uM for UDP-N-acetyl-D-glucosamine; PATHWAY: Protein modification; protein glycosylation. SUBUNIT: Heterotrimer; 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 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. INTERACTION: P51610:HCFC1; NbExp=9; IntAct=EBI-539828, EBI-396176; Q8IZD2:MLL5; NbExp=4; IntAct=EBI-539828, EBI-2689959; SUBCELLULAR LOCATION: Isoform 2: Mitochondrion. Membrane. Note=Associates with the mitochondrial inner membrane. SUBCELLULAR LOCATION: Isoform 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 LOCATION: Isoform 4: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver. INDUCTION: Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux. DOMAIN: The TPR repeat domain is required for substrate binding and oligomerization. PTM: Ubiquitinated, leading to its proteasomal degradation. DISEASE: Note=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. SIMILARITY: Belongs to the O-GlcNAc transferase family. SIMILARITY: Contains 13 TPR repeats. WEB RESOURCE: Name=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";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15294
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006110 regulation of glycolytic process GO:0006111 regulation of gluconeogenesis GO:0006325 chromatin organization GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006486 protein glycosylation GO:0006493 protein O-linked glycosylation GO:0006915 apoptotic process GO:0007165 signal transduction GO:0007584 response to nutrient GO:0016485 protein processing GO:0016579 protein deubiquitination GO:0031397 negative regulation of protein ubiquitination GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032868 response to insulin GO:0032922 circadian regulation of gene expression GO:0035020 regulation of Rac protein signal transduction GO:0043981 histone H4-K5 acetylation GO:0043982 histone H4-K8 acetylation GO:0043984 histone H4-K16 acetylation GO:0045862 positive regulation of proteolysis GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046626 regulation of insulin receptor signaling pathway GO:0048015 phosphatidylinositol-mediated signaling GO:0048511 rhythmic process GO:0061087 positive regulation of histone H3-K27 methylation GO:0080182 histone H3-K4 trimethylation
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
