OGT
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]
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) (PubMed:26678539, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:15361863).
Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1 (PubMed:19451179, PubMed:20200153, PubMed:21285374, PubMed:22923583, PubMed:23353889, PubMed:24474760, PubMed:26678539, PubMed:27527864).
Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374).
Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539).
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 (By similarity).
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:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863).
O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723).
Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity).
Glycosylates HOXA1 (By similarity).
O-glycosylates FNIP1 (PubMed:30699359).
Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864).
Isoform 2
The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.
Biological Process
Apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Chromatin organizationIEA:UniProtKB-KW
Circadian regulation of gene expressionISS:UniProtKB
HemopoiesisBy SimilarityISS:ARUK-UCL
Histone H3-K4 trimethylationManual Assertion Based On ExperimentIMP:UniProtKB
Histone H4-K16 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4-K5 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4-K8 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
MitophagyBy SimilarityISS:ARUK-UCL
Negative regulation of cell migration1 PublicationIC:ComplexPortal
Negative regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of stem cell population maintenance1 PublicationIC:ComplexPortal
Negative regulation of transcription by RNA polymerase II1 PublicationIC:ComplexPortal
Negative regulation of transforming growth factor beta receptor signaling pathway1 PublicationIC:ComplexPortal
Phosphatidylinositol-mediated signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Positive regulation of histone H3-K27 methylationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of histone H3-K4 methylationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of stem cell population maintenance1 PublicationIC:ComplexPortal
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templated1 PublicationIC:ComplexPortal
Protein O-linked glycosylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein processingManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of dosage compensation by inactivation of X chromosomeIEA:Ensembl
Regulation of gluconeogenesisISS:UniProtKB
Regulation of glycolytic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of insulin receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of necroptotic processTAS:Reactome
Regulation of Rac protein signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Response to insulinManual Assertion Based On ExperimentIDA:UniProtKB
Response to nutrientManual Assertion Based On ExperimentTAS:ProtInc
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Cellular Location
Nucleus
Cytoplasm
Predominantly localizes to the nucleus.
Isoform 2
Mitochondrion
Membrane
Associates with the mitochondrial inner membrane.
Isoform 3
Cytoplasm
Nucleus
Cell membrane
Mitochondrion membrane
Cell projection
Mostly in the nucleus. Retained in the nucleus via interaction with HCFC1 (PubMed:21285374).
After insulin induction, translocated from the nucleus to the cell membrane via phosphatidylinositide binding. Colocalizes with AKT1 at the plasma membrane. TRAK1 recruits this protein to mitochondria. In the absence of TRAK1, localizes in cytosol and nucleus (By similarity).
Isoform 4
Cytoplasm
Nucleus
Involvement in disease
Intellectual developmental disorder, X-linked 106 (XLID106):
A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
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