OGT
entrez
8473
canonical
uniprot
O15294
canonical
ensembl
ENSG00000147162
resolver
ensp
ENSP00000362805
resolver
ensp
ENSP00000362824
resolver
genesymbol
OGT
resolver
hgnc
HGNC:8127
resolver
uniprot
Q7Z3K0
resolver
uniprot
Q8WWM8
resolver
uniprot
Q96CC1
resolver
uniprot
Q9UG57
resolver
uniprot_entry
OGT1_HUMAN
resolver
uniprot_sec
Q7Z3K0
resolver
uniprot_sec
Q8WWM8
resolver
uniprot_sec
Q96CC1
resolver
uniprot_sec
Q9UG57
resolver
activity_regulation
ACTIVITY REGULATION: Subject to product inhibition by UDP. {ECO:0000269|PubMed:21240259}.
uniprot
proteins
amino_acid_sequence
MASSVGNVADSTEPTKRMLSFQGLAELAHREYQAGDFEAAERHCMQLWRQEPDNTGVLLLLSSIHFQCRRLDRSAHFSTLAIKQNPLLAEAYSNLGNVYKERGQLQEAIEHYRHALRLKPDFIDGYINLAAALVAAGDMEGAVQAYVSALQYNPDLYCVRSDLGNLLKALGRLEEAKACYLKAIETQPNFAVAWSNLGCVFNAQGEIWLAIHHFEKAVTLDPNFLDAYINLGNVLKEARIFDRAVAAYLRALSLSPNHAVVHGNLACVYYEQGLIDLAIDTYRRAIELQPHFPDAYCNLANALKEKGSVAEAEDCYNTALRLCPTHADSLNNLANIKREQGNIEEAVRLYRKALEVFPEFAAAHSNLASVLQQQGKLQEALMHYKEAIRISPTFADAYSNMGNTLKEMQDVQGALQCYTRAIQINPAFADAHSNLASIHKDSGNIPEAIASYRTALKLKPDFPDAYCNLAHCLQIVCDWTDYDERMKKLVSIVADQLEKNRLPSVHPHHSMLYPLSHGFRKAIAERHGNLCLDKINVLHKPPYEHPKDLKLSDGRLRVGYVSSDFGNHPTSHLMQSIPGMHNPDKFEVFCYALSPDDGTNFRVKVMAEANHFIDLSQIPCNGKAADRIHQDGIHILVNMNGYTKGARNELFALRPAPIQAMWLGYPGTSGALFMDYIITDQETSPAEVAEQYSEKLAYMPHTFFIGDHANMFPHLKKKAVIDFKSNGHIYDNRIVLNGIDLKAFLDSLPDVKIVKMKCPDGGDNADSSNTALNMPVIPMNTIAEAVIEMINRGQIQITINGFSISNGLATTQINNKAATGEEVPRTIIVTTRSQYGLPEDAIVYCNFNQLYKIDPSTLQMWANILKRVPNSVLWLLRFPAVGEPNIQQYAQNMGLPQNRIIFSPVAPKEEHVRRGQLADVCLDTPLCNGHTTGMDVLWAGTPMVTMPGETLASRVAASQLTCLGCLELIAKNRQEYEDIAVKLGTDLEYLKKVRGKVWKQRISSPLFNTKQYTMELERLYLQMWEHYAAGNKPDHMIKPVEVTESA
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:19451179}.; DISEASE: Intellectual developmental disorder, X-linked 106 (XLID106) [MIM:300997]: A form of intellectual disability, 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 forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:26273451, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.4.1.255
uniprot
proteins
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:12150998, PubMed:15361863, PubMed:19451179, PubMed:20018868, PubMed:21240259, PubMed:21285374, PubMed:23103939, PubMed:26237509, PubMed:26369908, PubMed:26678539, PubMed:27713473, PubMed:37541260, PubMed:37962578). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, AMPK, ATG4B, CAPRIN1, EZH2, FNIP1, GSDMD, KRT7, LMNA, LMNB1, LMNB2, RPTOR, HOXA1, PFKL, KMT2E/MLL5, MAPT/TAU, TET2, RBL2, RET, NOD2 and HCFC1 (PubMed:19451179, PubMed:20200153, PubMed:21285374, PubMed:22923583, PubMed:23353889, PubMed:24474760, PubMed:26237509, PubMed:26369908, PubMed:26678539, PubMed:27527864, PubMed:30699359, PubMed:34074792, PubMed:34667079, PubMed:37541260, PubMed:37962578). Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). 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). 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). Stabilizes KMT2E/MLL5 by mediating its glycosylation, thereby preventing KMT2E/MLL5 ubiquitination (PubMed:26678539). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver (By similarity). Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation (By similarity). 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 (PubMed:21285374, PubMed:28302723, PubMed:28584052). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864). Acts as a regulator of mTORC1 signaling by mediating O-glycosylation of RPTOR and FNIP1: O-GlcNAcylation of RPTOR in response to glucose sufficiency promotes activation of the mTORC1 complex (PubMed:30699359, PubMed:37541260). {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:24563466, ECO:0000269|PubMed:26237509, ECO:0000269|PubMed:26369908, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27527864, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:34074792, ECO:0000269|PubMed:34667079, ECO:0000269|PubMed:37541260, ECO:0000269|PubMed:37962578}.; 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}.; FUNCTION: [Isoform 4]: Has N-acetylglucosaminyltransferase activity: glycosylates proteins, such as HNRNPU, NEUROD1, NUP62 and PDCD6IP (PubMed:31527085). Displays specific substrate selectivity compared to other isoforms (PubMed:31527085). {ECO:0000269|PubMed:31527085}.
uniprot
proteins
mass_dalton
116925
uniprot
proteins
mutagenesis
MUTAGEN 208..211; /note="WLAI->ELAD: Abolished homooligomerization."; /evidence="ECO:0000269|PubMed:27713473"; MUTAGEN 208; /note="W->E: Abolishes homodimerization of the TPR domain. Slightly reduced enzyme activity; when associated with D-211."; /evidence="ECO:0000269|PubMed:15361863"; MUTAGEN 211; /note="I->D: Abolishes homodimerization of the TPR domain. Slightly reduced enzyme activity; when associated with E-208."; /evidence="ECO:0000269|PubMed:15361863"; MUTAGEN 391; /note="S->A: Reduced autoglycosylation."; /evidence="ECO:0000269|PubMed:27713473"; MUTAGEN 393; /note="T->V: Reduced autoglycosylation."; /evidence="ECO:0000269|PubMed:27713473"; MUTAGEN 399; /note="S->A: Reduced autoglycosylation. Reduced localization to the nucleus."; /evidence="ECO:0000269|PubMed:27713473"; MUTAGEN 404; /note="T->V: Reduced autoglycosylation."; /evidence="ECO:0000269|PubMed:27713473"; MUTAGEN 454; /note="T->A: Abolished phosphorylation by AMPK. Does not affect ability to regulate mTORC1."; /evidence="ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:37541260"; MUTAGEN 454; /note="T->E: Affects substrate selectivity. Mimics phosphorylation; does not affect ability to regulate mTORC1."; /evidence="ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:37541260"; MUTAGEN 461..463; /note="DFP->AAA: Impaired localization to the nucleus."; /evidence="ECO:0000269|PubMed:37541260"; MUTAGEN 508; /note="H->A: Loss of enzyme activity. Moderate increase in KMT2E ubiquitination. Moderate increase in KMT2E ubiquitination; when associated with A-508."; /evidence="ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:26678539"; MUTAGEN 568; /note="H->A: Reduces enzyme activity by about 95%. Moderate increase in KMT2E ubiquitination; when associated with A-508."; /evidence="ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:26678539"; MUTAGEN 911; /note="H->A: Reduces enzyme activity by over 90%."; /evidence="ECO:0000269|PubMed:21240259"; MUTAGEN O15294-4:10; /note="S->A: Does not affect global auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:12; /note="T->A: Decreased auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:18; /note="S->A: Does not affect global auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:38; /note="T->A: Does not affect global auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:52; /note="S->A: Does not affect global auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:56; /note="S->A: Increased auto-O-GlcNAcylation."; /evidence="ECO:0000269|PubMed:31527085"; MUTAGEN O15294-4:127; /note="H->A: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:31527085
uniprot
proteins
pathway_participation
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, ECO:0000269|PubMed:27713473, ECO:0000269|PubMed:31527085, ECO:0000269|PubMed:37541260}.
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by the SCF(FBXO31) complex, leading to its proteasomal degradation. {ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:39894887}.; PTM: Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity (By similarity). Phosphorylation at Thr-454 by AMPK promotes nuclear localization (PubMed:24563466). {ECO:0000250|UniProtKB:Q8CGY8, ECO:0000269|PubMed:24563466}.; PTM: Glycosylated via autocatalysis; O-GlcNAcylation at Ser-399 promotes nuclear localization. {ECO:0000269|PubMed:27713473}.; PTM: [Isoform 4]: Glycosylated via autocatalysis; does not affect the enzyme activity but regulates substrate selectivity. {ECO:0000269|PubMed:31527085}.
uniprot
proteins
protein_family
Glycosyltransferase 41 family
uniprot
proteins
protein_family
O-GlcNAc transferase subfamily
uniprot
proteins
pubmed
11773972
uniprot
proteins
pubmed
12150998
uniprot
proteins
pubmed
12670868
uniprot
proteins
pubmed
15361863
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19073609
uniprot
proteins
pubmed
19377461
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19451179
uniprot
proteins
pubmed
20018852
uniprot
proteins
pubmed
20018868
uniprot
proteins
pubmed
20200153
uniprot
proteins
pubmed
20824293
uniprot
proteins
pubmed
21240259
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21285374
uniprot
proteins
pubmed
22121020
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
22923583
uniprot
proteins
pubmed
23103939
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23222540
uniprot
proteins
pubmed
23353889
uniprot
proteins
pubmed
23629655
uniprot
proteins
pubmed
24336203
uniprot
proteins
pubmed
24474760
uniprot
proteins
pubmed
24563466
uniprot
proteins
pubmed
24995978
uniprot
proteins
pubmed
26237509
uniprot
proteins
pubmed
26273451
uniprot
proteins
pubmed
26369908
uniprot
proteins
pubmed
26678539
uniprot
proteins
pubmed
27527864
uniprot
proteins
pubmed
27713473
uniprot
proteins
pubmed
28302723
uniprot
proteins
pubmed
28584052
uniprot
proteins
pubmed
28742148
uniprot
proteins
pubmed
30699359
uniprot
proteins
pubmed
31527085
uniprot
proteins
pubmed
34074792
uniprot
proteins
pubmed
34667079
uniprot
proteins
pubmed
37541260
uniprot
proteins
pubmed
37962578
uniprot
proteins
pubmed
39894887
uniprot
proteins
pubmed
9083068
uniprot
proteins
sequence_length
1046
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27713473}. Cytoplasm {ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27713473}. Note=Predominantly localizes to the nucleus (PubMed:26678539). Translocates into the nucleus via association with importin KPNA1 (PubMed:27713473). {ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27713473}.; 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 {ECO:0000303|PubMed:31527085}. Nucleus {ECO:0000303|PubMed:31527085}.
uniprot
proteins