Names & Taxonomy
- Uniprot ID:
- O15294
- Entry Name:
- OGT1_HUMAN
- Status:
- reviewed
- Protein Names:
- UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit (EC 2.4.1.255) (O-GlcNAc transferase subunit p110) (O-linked N-acetylglucosamine transferase 110 kDa subunit) (OGT)
- Gene Names:
- OGT
- Gene Names Primary:
- OGT
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1046
- Sequence:
- MASSVGNVADSTEPTKRMLSFQGLAELAHREYQAGDFEAAERHCMQLWRQEPDNTGVLLLLSSIHFQCRRLDRSAHFSTLAIKQNPLLAEAYSNLGNVYKERGQLQEAIEHYRHALRLKPDFIDGYINLAAALVAAGDMEGAVQAYVSALQYNPDLYCVRSDLGNLLKALGRLEEAKACYLKAIETQPNFAVAWSNLGCVFNAQGEIWLAIHHFEKAVTLDPNFLDAYINLGNVLKEARIFDRAVAAYLRALSLSPNHAVVHGNLACVYYEQGLIDLAIDTYRRAIELQPHFPDAYCNLANALKEKGSVAEAEDCYNTALRLCPTHADSLNNLANIKREQGNIEEAVRLYRKALEVFPEFAAAHSNLASVLQQQGKLQEALMHYKEAIRISPTFADAYSNMGNTLKEMQDVQGALQCYTRAIQINPAFADAHSNLASIHKDSGNIPEAIASYRTALKLKPDFPDAYCNLAHCLQIVCDWTDYDERMKKLVSIVADQLEKNRLPSVHPHHSMLYPLSHGFRKAIAERHGNLCLDKINVLHKPPYEHPKDLKLSDGRLRVGYVSSDFGNHPTSHLMQSIPGMHNPDKFEVFCYALSPDDGTNFRVKVMAEANHFIDLSQIPCNGKAADRIHQDGIHILVNMNGYTKGARNELFALRPAPIQAMWLGYPGTSGALFMDYIITDQETSPAEVAEQYSEKLAYMPHTFFIGDHANMFPHLKKKAVIDFKSNGHIYDNRIVLNGIDLKAFLDSLPDVKIVKMKCPDGGDNADSSNTALNMPVIPMNTIAEAVIEMINRGQIQITINGFSISNGLATTQINNKAATGEEVPRTIIVTTRSQYGLPEDAIVYCNFNQLYKIDPSTLQMWANILKRVPNSVLWLLRFPAVGEPNIQQYAQNMGLPQNRIIFSPVAPKEEHVRRGQLADVCLDTPLCNGHTTGMDVLWAGTPMVTMPGETLASRVAASQLTCLGCLELIAKNRQEYEDIAVKLGTDLEYLKKVRGKVWKQRISSPLFNTKQYTMELERLYLQMWEHYAAGNKPDHMIKPVEVTESA
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Isoform 2: Mitochondrion. Membrane. Note=Associates with the mitochondrial inner membrane.; 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.; Isoform 4: Cytoplasm. Nucleus.
Function
- 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, 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).
- Pathway:
- Protein modification; protein glycosylation.
- Catalytic Activity:
- UDP-N-acetyl-alpha-D-glucosamine + -L-serine = UDP + -3-O-(N-acetyl-beta-D-glucosaminyl)-L-serine.
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.8 uM for UDP-N-acetyl-D-glucosamine
- Enzyme Regulation:
- ENZYME REGULATION: Subject to product inhibition by UDP.
- Active Site:
- ACT_SITE 508 508 Proton acceptor.
- Gene Ontology Go:
- cytosol
euchromatin
histone acetyltransferase complex
mitochondrion
MLL5-L complex
neuron projection
neuronal cell body
nucleoplasm
nucleus
plasma membrane
zymogen granule
acetylglucosaminyltransferase activity
enzyme activator activity
monosaccharide binding
peptide binding
phosphatidylinositol-3,4,5-trisphosphate binding
protein N-acetylglucosaminyltransferase activity
protein O-GlcNAc transferase activity
apoptotic process
cellular response to glucose stimulus
cellular response to insulin stimulus
cellular response to lipopolysaccharide
cellular response to retinoic acid
cellular response to toxic substance
chromatin organization
circadian regulation of gene expression
forebrain development
glucosamine metabolic process
histone H3-K4 trimethylation
histone H4-K16 acetylation
histone H4-K5 acetylation
histone H4-K8 acetylation
intracellular distribution of mitochondria
negative regulation of cell death
negative regulation of cellular response to hypoxia
negative regulation of peptidyl-serine phosphorylation
negative regulation of peptidyl-threonine phosphorylation
negative regulation of protein targeting to membrane
negative regulation of protein ubiquitination
phosphatidylinositol-mediated signaling
positive regulation of catalytic activity
positive regulation of cell size
positive regulation of granulocyte differentiation
positive regulation of histone H3-K27 methylation
positive regulation of histone H3-K4 methylation
positive regulation of protein localization to nucleus
positive regulation of protein phosphorylation
positive regulation of proteolysis
positive regulation of reactive oxygen species biosynthetic process
positive regulation of transcription from RNA polymerase II promoter
protein heterotrimerization
protein homotrimerization
protein O-linked glycosylation
regulation of gluconeogenesis involved in cellular glucose homeostasis
regulation of glycolytic process
regulation of insulin receptor signaling pathway
regulation of Rac protein signal transduction
response to insulin
response to nutrient
signal transduction - Gene Ontology Biological Process:
- apoptotic process
cellular response to glucose stimulus
cellular response to insulin stimulus
cellular response to lipopolysaccharide
cellular response to retinoic acid
cellular response to toxic substance
chromatin organization
circadian regulation of gene expression
forebrain development
glucosamine metabolic process
histone H3-K4 trimethylation
histone H4-K16 acetylation
histone H4-K5 acetylation
histone H4-K8 acetylation
intracellular distribution of mitochondria
negative regulation of cell death
negative regulation of cellular response to hypoxia
negative regulation of peptidyl-serine phosphorylation
negative regulation of peptidyl-threonine phosphorylation
negative regulation of protein targeting to membrane
negative regulation of protein ubiquitination
phosphatidylinositol-mediated signaling
positive regulation of catalytic activity
positive regulation of cell size
positive regulation of granulocyte differentiation
positive regulation of histone H3-K27 methylation
positive regulation of histone H3-K4 methylation
positive regulation of protein localization to nucleus
positive regulation of protein phosphorylation
positive regulation of proteolysis
positive regulation of reactive oxygen species biosynthetic process
positive regulation of transcription from RNA polymerase II promoter
protein heterotrimerization
protein homotrimerization
protein O-linked glycosylation
regulation of gluconeogenesis involved in cellular glucose homeostasis
regulation of glycolytic process
regulation of insulin receptor signaling pathway
regulation of Rac protein signal transduction
response to insulin
response to nutrient
signal transduction - Gene Ontology Molecular Function:
- acetylglucosaminyltransferase activity
enzyme activator activity
monosaccharide binding
peptide binding
phosphatidylinositol-3,4,5-trisphosphate binding
protein N-acetylglucosaminyltransferase activity
protein O-GlcNAc transferase activity - Gene Ontology Cellular Component:
- cytosol
euchromatin
histone acetyltransferase complex
mitochondrion
MLL5-L complex
neuronal cell body
neuron projection
nucleoplasm
nucleus
plasma membrane
zymogen granule - Keywords:
- 3D-structure
Acetylation
Alternative splicing
Apoptosis
Biological rhythms
Cell membrane
Chromatin regulator
Complete proteome
Cytoplasm
Direct protein sequencing
Glycoprotein
Glycosyltransferase
Lipid-binding
Membrane
Mitochondrion
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
TPR repeat
Transferase
Ubl conjugation - Interacts With:
- P51610; P09022; O95644; Q9H1M0; Q8NDX5; P11464; Q04206; E7EQS8; Q6N021; O43151; Q8BG87; Q9UPV9