Protein: 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) (P56558)
Organism: Rattus norvegicus (Rat)
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). Has 3 distinct KM values for UDP-GlcNAc; GlcNAc concentration modulates its affinity for different substrates. Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, 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. Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (By similarity). 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. 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). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues. O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex. Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (By similarity). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1. Glycosylates HOXA1 (By similarity). O-glycosylates FNIP1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:1533623, ECO:0000269|PubMed:16714295, ECO:0000269|PubMed:24995978, ECO:0000269|PubMed:9083067}. Nucleus {ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:24995978, ECO:0000269|PubMed:9083067}. Cell membrane {ECO:0000269|PubMed:18288188}. Mitochondrion membrane {ECO:0000269|PubMed:24995978}. Cell projection {ECO:0000269|PubMed:24995978}. Note=Mostly in the nucleus (PubMed:9083067). After insulin induction, translocated from the nucleus to the cell membrane via phosphatidylinositide binding. Colocalizes with AKT1 at the plasma membrane (PubMed:18288188). TRAK1 recruits this protein to mitochondria (PubMed:24995978). In the absence of TRAK1, localizes in cytosol and nucleus (PubMed:24995978). Translocates into the nucleus via association with importin KPNA1 (By similarity). {ECO:0000250|UniProtKB:O15294, ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:24995978, ECO:0000305|PubMed:9083067}.
Interaction partners:
- Host cell factor 1
- EGF domain-specific O-linked N-acetylglucosamine transferase
- KAT8 regulatory NSL complex subunit 3
- Microspherule protein 1
- Forkhead box protein K1
- CREB-regulated transcription coactivator 2
- RAC-alpha serine/threonine-protein kinase
- KAT8 regulatory NSL complex subunit 2
- Glycogen [starch] synthase, muscle
- Glycogen [starch] synthase, liver
Sequence:
MASSVGNVADSTGLAELAHREYQAGDFEAAERHCMQLWRQEPDNTGVLLLLSSIHFQCRRLDRSAHFSTLAIKQNPLLAEAYSNLGNVYKERGQLQEAIEHYRHALRLKPDFIDGYINLAAALVAAGDMEGAVQAYVSALQYNPDLYCVRSDLGNLLKALGRLEEAKACYLKAIETQPNFAVAWSNLGCVFNAQGEIWLAIHHFEKAVTLDPNFLDAYINLGNVLKEARIFDRAVAAYLRALSLSPNHAVVHGNLACVYYEQGLIDLAIDTYRRAIELQPHFPDAYCNLANALKEKGSVAEAEDCYNTALRLCPTHADSLNNLANIKREQGNIEEAVRLYRKALEVFPEFAAAHSNLASVLQQQGKLQEALMHYKEAIRISPTFADAYSNMGNTLKEMQDVQGALQCYTRAIQINPAFADAHSNLASIHKDSGNIPEAIASYRTALKLKPDFPDAYCNLAHCLQIVCDWTDYDERMKKLVSIVAEQLEKNRLPSVHPHHSMLYPLSHGFRKAIAERHGNLCLDKINVLHKPPYEHPKDLKLSDGRLRVGYVSSDFGNHPTSHLMQSIPGMHNPDKFEVFCYALSPDDGTNFRVKVMAEANHFIDLSQIPCNGKAADRIHQDGIHILVNMNGYTKGARNELFALRPAPIQAMWLGYPGTSGALFMDYIITDQETSPAEVAEQYSEKLAYMPHTFFIGDHANMFPHLKKKAVIDFKSNGHIYDNRIVLNGIDLKAFLDSLPDVKIVKMKCPDGGDNADTTNTALNMPVIPMNTIAEAVIEMINRGQIQITINGFSISNGLATTQINNKAATGEEVPRTIIVTTRSQYGLPEDAIVYCNFNQLYKIDPSTLQMGANILKRVPNSVLWLLRFPAVGEPNIQQYAQNMGLPQNRIIFSPVAPKEEHVRRGQLADVCLDTPLCNGHTTGMDVLWAGTPMVTMPGETLASRVAASQLTCLGCLELIAKSRQEYEDIAVKLGTDLEYLKKIRGKVWKQRISSPLFNTKQYTMELERLYLQMWEHYAAGNKPDHMIKPVEVTESA