Human Gene OGT (uc004eaa.2) Description and Page Index
Description: Homo sapiens O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), transcript variant 1, mRNA. RefSeq Summary (NM_181672): This gene encodes a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. Since both phosphorylation and glycosylation compete for similar serine or threonine residues, the two processes may compete for sites, or they may alter the substrate specificity of nearby sites by steric or electrostatic effects. The protein contains multiple tetratricopeptide repeats that are required for optimal recognition of substrates. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2009]. Transcript (Including UTRs) Position: hg19 chrX:70,752,912-70,795,747 Size: 42,836 Total Exon Count: 22 Strand: + Coding Region Position: hg19 chrX:70,753,150-70,793,644 Size: 40,495 Coding Exon Count: 22
ID:OGT1_HUMAN DESCRIPTION: RecName: Full=UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit; EC=184.108.40.206; 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";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): OGT CDC HuGE Published Literature: OGT
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.