Human Gene OGT (uc004eaa.2) Description and Page Index
  Description: Homo sapiens O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), transcript variant 1, mRNA.
RefSeq Summary (NM_181672): 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].
Transcript (Including UTRs)
   Position: hg19 chrX:70,752,912-70,795,747 Size: 42,836 Total Exon Count: 22 Strand: +
Coding Region
   Position: hg19 chrX:70,753,150-70,793,644 Size: 40,495 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:70,752,912-70,795,747)mRNA (may differ from genome)Protein (1046 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: OGT1_HUMAN
DESCRIPTION: RecName: Full=UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit; EC=2.4.1.255; AltName: Full=O-GlcNAc transferase subunit p110; AltName: Full=O-linked N-acetylglucosamine transferase 110 kDa subunit; Short=OGT;
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, PFKL, 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. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues.
FUNCTION: Isoform 2, the mitochondrial isoform (mOGT), is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.
CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + [protein]-L- serine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine.
CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + [protein]-L- threonine = UDP + [protein]-3-O-(N-acetyl-D-glucosaminyl)-L- threonine.
ENZYME REGULATION: Subject to product inhibition by UDP.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.8 uM for UDP-N-acetyl-D-glucosamine;
PATHWAY: Protein modification; protein glycosylation.
SUBUNIT: Heterotrimer; consists of one 78 kDa subunit and two 110 kDa subunits dimerized via TPR repeats 6 and 7. Interacts (via TPR repeats 6 and 7) with ATXN10 (By similarity). Component of the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, PPP1CB, HCFC1, PPP1CC and ACTB. Component of a THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O- glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase.
INTERACTION: P51610:HCFC1; NbExp=9; IntAct=EBI-539828, EBI-396176; Q8IZD2:MLL5; NbExp=4; IntAct=EBI-539828, EBI-2689959;
SUBCELLULAR LOCATION: Isoform 2: Mitochondrion. Membrane. Note=Associates with the mitochondrial inner membrane.
SUBCELLULAR LOCATION: 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.
SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus.
TISSUE SPECIFICITY: Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver.
INDUCTION: Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux.
DOMAIN: The TPR repeat domain is required for substrate binding and oligomerization.
PTM: Ubiquitinated, leading to its proteasomal degradation.
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.
SIMILARITY: Belongs to the O-GlcNAc transferase family.
SIMILARITY: Contains 13 TPR repeats.
WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=UDP- N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110kDa subunit; URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_554";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): OGT
CDC HuGE Published Literature: OGT

-  MalaCards Disease Associations
  MalaCards Gene Search: OGT
Diseases sorted by gene-association score: mental retardation, x-linked 106* (900), adams-oliver syndrome (6), spinocerebellar ataxia 10 (5), bardet-biedl syndrome 4 (4), alzheimer disease (3), diabetes mellitus, noninsulin-dependent (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D000082 Acetaminophen
  • D002945 Cisplatin
  • D008070 Lipopolysaccharides
  • D013749 Tetrachlorodibenzodioxin
  • C006253 pirinixic acid
  • C023514 2,6-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D015124 8-Bromo Cyclic Adenosine Monophosphate
  • C547126 AZM551248
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 119.53 RPKM in Spleen
Total median expression: 2801.23 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -81.42238-0.342 Picture PostScript Text
3' UTR -571.112103-0.272 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001440 - TPR-1
IPR013026 - TPR-contain_dom
IPR011990 - TPR-like_helical
IPR019734 - TPR_repeat

Pfam Domains:
PF00515 - Tetratricopeptide repeat
PF07719 - Tetratricopeptide repeat
PF13176 - Tetratricopeptide repeat
PF13181 - Tetratricopeptide repeat
PF13374 - Tetratricopeptide repeat
PF13414 - TPR repeat
PF13424 - Tetratricopeptide repeat
PF13431 - Tetratricopeptide repeat
PF13432 - Tetratricopeptide repeat
PF13844 - Glycosyl transferase family 41
PF14559 - Tetratricopeptide repeat

SCOP Domains:
81901 - HCP-like
48439 - Protein prenylyltransferase
48452 - TPR-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1W3B
- X-ray MuPIT

3PE3
- X-ray MuPIT

3PE4
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3TAX - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O15294
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
GO:0008289 lipid binding
GO:0008375 acetylglucosaminyltransferase activity
GO:0016262 protein N-acetylglucosaminyltransferase activity
GO:0016740 transferase activity
GO:0016757 transferase activity, transferring glycosyl groups
GO:0097363 protein O-GlcNAc transferase activity
GO:0043995 histone acetyltransferase activity (H4-K5 specific)
GO:0043996 histone acetyltransferase activity (H4-K8 specific)
GO:0046972 histone acetyltransferase activity (H4-K16 specific)

Biological Process:
GO:0006110 regulation of glycolytic process
GO:0006111 regulation of gluconeogenesis
GO:0006325 chromatin organization
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006486 protein glycosylation
GO:0006493 protein O-linked glycosylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007584 response to nutrient
GO:0016485 protein processing
GO:0016579 protein deubiquitination
GO:0031397 negative regulation of protein ubiquitination
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032868 response to insulin
GO:0032922 circadian regulation of gene expression
GO:0035020 regulation of Rac protein signal transduction
GO:0043981 histone H4-K5 acetylation
GO:0043982 histone H4-K8 acetylation
GO:0043984 histone H4-K16 acetylation
GO:0045862 positive regulation of proteolysis
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046626 regulation of insulin receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048511 rhythmic process
GO:0061087 positive regulation of histone H3-K27 methylation
GO:0080182 histone H3-K4 trimethylation

Cellular Component:
GO:0000123 histone acetyltransferase complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  AL833085 - Homo sapiens mRNA; cDNA DKFZp451K0919 (from clone DKFZp451K0919); complete cds.
BX537844 - Homo sapiens mRNA; cDNA DKFZp686C1753 (from clone DKFZp686C1753); complete cds.
BC038180 - Homo sapiens O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase), mRNA (cDNA clone MGC:39117 IMAGE:5017795), complete cds.
BC014434 - Homo sapiens O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase), mRNA (cDNA clone MGC:22921 IMAGE:4865031), complete cds.
DQ896848 - Synthetic construct Homo sapiens clone IMAGE:100011308; FLH184569.01L; RZPDo839H05143D O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase) (OGT) gene, encodes complete protein.
DQ893623 - Synthetic construct clone IMAGE:100006253; FLH184573.01X; RZPDo839H05144D O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase) (OGT) gene, encodes complete protein.
AB489152 - Synthetic construct DNA, clone: pF1KB0054, Homo sapiens OGT gene for O-linked N-acetylglucosamine (GlcNAc) transferase, without stop codon, in Flexi system.
AL050366 - Homo sapiens mRNA; cDNA DKFZp564A126 (from clone DKFZp564A126); partial cds.
AK313530 - Homo sapiens cDNA, FLJ94088.
U77413 - Human O-linked GlcNAc transferase mRNA, complete cds.
AF223393 - Homo sapiens HRNT1 mRNA, complete cds.
AK300267 - Homo sapiens cDNA FLJ61388 complete cds, highly similar to UDP-N-acetylglucosamine--peptideN-acetylglucosaminyltransferase 110 kDa subunit (EC 2.4.1.-).
AK026724 - Homo sapiens cDNA: FLJ23071 fis, clone LNG05694.
JD103910 - Sequence 84934 from Patent EP1572962.
JD538619 - Sequence 519643 from Patent EP1572962.
CU676989 - Synthetic construct Homo sapiens gateway clone IMAGE:100020531 5' read OGT mRNA.
AF147394 - Homo sapiens full length insert cDNA clone YI62A04.
JD052062 - Sequence 33086 from Patent EP1572962.
JD160286 - Sequence 141310 from Patent EP1572962.
AL049950 - Homo sapiens mRNA; cDNA DKFZp564M1922 (from clone DKFZp564M1922).
JD327093 - Sequence 308117 from Patent EP1572962.
JD188019 - Sequence 169043 from Patent EP1572962.
JD276687 - Sequence 257711 from Patent EP1572962.
JD416910 - Sequence 397934 from Patent EP1572962.
JD277490 - Sequence 258514 from Patent EP1572962.
AF070560 - Homo sapiens clone 24689 mRNA sequence.
JD566721 - Sequence 547745 from Patent EP1572962.
JD528835 - Sequence 509859 from Patent EP1572962.
JD160210 - Sequence 141234 from Patent EP1572962.
BC015144 - Homo sapiens cDNA clone IMAGE:4044075.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O15294 (Reactome details) participates in the following event(s):

R-HSA-3321805 NSL acetylates histone H4
R-HSA-5689630 BAP1 binds BAP1-interacting complex
R-HSA-3214847 HATs acetylate histones
R-HSA-5689603 UCH proteinases
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-5688426 Deubiquitination
R-HSA-4839726 Chromatin organization
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: NM_181672, NP_858058, O15294, OGT1_HUMAN, Q7Z3K0, Q8WWM8, Q96CC1, Q9UG57
UCSC ID: uc004eaa.2
RefSeq Accession: NM_181672
Protein: O15294 (aka OGT1_HUMAN)
CCDS: CCDS14414.1, CCDS35502.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_181672.2
exon count: 22CDS single in 3' UTR: no RNA size: 5497
ORF size: 3141CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6186.50frame shift in genome: no % Coverage: 99.73
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.