| IED ID | IndEnz0002001137 |
| Enzyme Type ID | protease001137 |
| Protein Name |
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 Name | OGT |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MASSVGNVADSTEPTKRMLSFQGLAELAHREYQAGDFEAAERHCMQLWRQEPDNTGVLLLLSSIHFQCRRLDRSAHFSTLAIKQNPLLAEAYSNLGNVYKERGQLQEAIEHYRHALRLKPDFIDGYINLAAALVAAGDMEGAVQAYVSALQYNPDLYCVRSDLGNLLKALGRLEEAKACYLKAIETQPNFAVAWSNLGCVFNAQGEIWLAIHHFEKAVTLDPNFLDAYINLGNVLKEARIFDRAVAAYLRALSLSPNHAVVHGNLACVYYEQGLIDLAIDTYRRAIELQPHFPDAYCNLANALKEKGSVAEAEDCYNTALRLCPTHADSLNNLANIKREQGNIEEAVRLYRKALEVFPEFAAAHSNLASVLQQQGKLQEALMHYKEAIRISPTFADAYSNMGNTLKEMQDVQGALQCYTRAIQINPAFADAHSNLASIHKDSGNIPEAIASYRTALKLKPDFPDAYCNLAHCLQIVCDWTDYDERMKKLVSIVADQLEKNRLPSVHPHHSMLYPLSHGFRKAIAERHGNLCLDKINVLHKPPYEHPKDLKLSDGRLRVGYVSSDFGNHPTSHLMQSIPGMHNPDKFEVFCYALSPDDGTNFRVKVMAEANHFIDLSQIPCNGKAADRIHQDGIHILVNMNGYTKGARNELFALRPAPIQAMWLGYPGTSGALFMDYIITDQETSPAEVAEQYSEKLAYMPHTFFIGDHANMFPHLKKKAVIDFKSNGHIYDNRIVLNGIDLKAFLDSLPDVKIVKMKCPDGGDNADSSNTALNMPVIPMNTIAEAVIEMINRGQIQITINGFSISNGLATTQINNKAATGEEVPRTIIVTTRSQYGLPEDAIVYCNFNQLYKIDPSTLQMWANILKRVPNSVLWLLRFPAVGEPNIQQYAQNMGLPQNRIIFSPVAPKEEHVRRGQLADVCLDTPLCNGHTTGMDVLWAGTPMVTMPGETLASRVAASQLTCLGCLELIAKNRQEYEDIAVKLGTDLEYLKKVRGKVWKQRISSPLFNTKQYTMELERLYLQMWEHYAAGNKPDHMIKPVEVTESA |
| Enzyme Length | 1046 |
| Uniprot Accession Number | O15294 |
| Absorption | |
| Active Site | ACT_SITE 508; /note="Proton acceptor"; /evidence="ECO:0000305|PubMed:21240259, ECO:0000305|PubMed:26678539" |
| Activity Regulation | ACTIVITY REGULATION: Subject to product inhibition by UDP. {ECO:0000269|PubMed:21240259}. |
| Binding Site | BINDING 849; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW"; BINDING 852; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW"; BINDING 935; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl)-L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:48904, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:12251, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:90838; EC=2.4.1.255; Evidence={ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:30699359, ECO:0000305|PubMed:26678539};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48905; Evidence={ECO:0000269|PubMed:30699359}; CATALYTIC ACTIVITY: Reaction=L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:48908, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:12252, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:90840; EC=2.4.1.255; Evidence={ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000305|PubMed:26678539}; |
| DNA Binding | |
| EC Number | 2.4.1.255 |
| Enzyme 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) (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). {ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8, ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:19451179, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20018868, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:22121020, ECO:0000269|PubMed:22923583, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27527864, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052, ECO:0000269|PubMed:30699359}.; FUNCTION: [Isoform 2]: The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. {ECO:0000269|PubMed:20824293}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein glycosylation. {ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:26678539}. |
| nucleotide Binding | NP_BIND 906..908; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW"; NP_BIND 911..914; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW"; NP_BIND 930..932; /note="UDP"; /evidence="ECO:0000269|PubMed:23103939, ECO:0007744|PDB:4GYW" |
| Features | Active site (1); Alternative sequence (3); Beta strand (26); Binding site (3); Chain (1); Glycosylation (2); Helix (61); Initiator methionine (1); Modified residue (5); Motif (1); Mutagenesis (5); Natural variant (4); Nucleotide binding (3); Region (1); Repeat (13); Sequence conflict (2); Turn (4) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Apoptosis;Biological rhythms;Cell membrane;Cell projection;Chromatin regulator;Cytoplasm;Direct protein sequencing;Disease variant;Glycoprotein;Glycosyltransferase;Host-virus interaction;Lipid-binding;Membrane;Mental retardation;Mitochondrion;Nucleus;Phosphoprotein;Reference proteome;Repeat;TPR repeat;Transferase;Ubl conjugation;Ubl conjugation pathway |
| Interact With | P51610; O95644; Q9H1M0; Q8NDX5; P36873; P11464; Q04206; O95721; Q15750; E7EQS8; Q6N021; Q6N021-1; O43151; Q9UPV9; O94763; O94763-1; P09022; P63088; Q8BG87; A0A0S2Z5B5; Q9H1M0; Q9UHR5; Q8N9R8; Q15973 |
| Induction | INDUCTION: Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux. {ECO:0000269|PubMed:19073609}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26678539}. Cytoplasm {ECO:0000269|PubMed:26678539}. Note=Predominantly localizes to the nucleus. {ECO:0000269|PubMed:26678539}.; SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion {ECO:0000269|PubMed:20824293}. Membrane {ECO:0000269|PubMed:20824293}. Note=Associates with the mitochondrial inner membrane. {ECO:0000269|PubMed:20824293}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:21285374}. Nucleus {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:21285374}. Cell membrane {ECO:0000250|UniProtKB:P56558}. Mitochondrion membrane {ECO:0000250|UniProtKB:P56558}. Cell projection {ECO:0000250|UniProtKB:P56558}. Note=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). {ECO:0000250|UniProtKB:P56558, ECO:0000269|PubMed:21285374}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm. Nucleus. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"; MOD_RES 3; /note="Phosphoserine; by GSK3-beta; alternate"; /evidence="ECO:0000250|UniProtKB:Q8CGY8"; MOD_RES 4; /note="Phosphoserine; by GSK3-beta; alternate"; /evidence="ECO:0000250|UniProtKB:Q8CGY8"; MOD_RES 20; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 989; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:P56558" |
| Post Translational Modification | PTM: Ubiquitinated, leading to its proteasomal degradation. {ECO:0000269|PubMed:21285374}.; PTM: Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity. {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (37) |
| Cross Reference PDB | 1W3B; 3PE3; 3PE4; 3TAX; 4AY5; 4AY6; 4CDR; 4GYW; 4GYY; 4GZ3; 4GZ5; 4GZ6; 4N39; 4N3A; 4N3B; 4N3C; 4XI9; 4XIF; 5BNW; 5C1D; 5HGV; 5LVV; 5LWV; 5NPR; 5NPS; 5VIE; 5VIF; 6E37; 6EOU; 6IBO; 6MA1; 6MA2; 6MA3; 6MA4; 6MA5; 6Q4M; 6TKA; |
| Mapped Pubmed ID | 16189514; 16449650; 17000644; 17353931; 17882263; 19524512; 19615732; 19932102; 20360068; 20711500; 20805357; 21295698; 21516116; 21851590; 22082911; 22575643; 22817896; 23088713; 23103942; 23395175; 24256146; 24311690; 25416956; 25609649; 26237509; 26496610; 26638075; 27618188; 28659383; 29021254; 29058723; 29606577; 29681455; 29723473; 30285435; 30770249; 31296563; 31626249; 31695185; 32092778; |
| Motif | MOTIF 487..503; /note=Nuclear localization signal; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 116,925 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.8 uM for UDP-N-acetyl-D-glucosamine {ECO:0000269|PubMed:21240259}; |
| Metal Binding | |
| Rhea ID | RHEA:48904; RHEA:48905; RHEA:48908 |
| Cross Reference Brenda | 2.4.1.255; |