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FLASH GENE

Symbol

OGT

contributors: mct/pgu - updated : 21-11-2016

HGNC name	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)
HGNC id	8127

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth       highly Endocrine pancreas       highly Lymphoid/Immune spleen       moderately   thymus       highly Nervous brain       highly Homo sapiens Respiratory respiratory tract larynx     highly   respiratory tract trachea     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal region consisting of a series of tetratricopeptide repeat (TPR) units19, 20 and a multidomain catalytic region
	thirteen tetratricopeptide (TPR) repeats (twelve full domain and one truncated) interacting with the coiled-coil domains of ALS2CR3 and OIP106
	a possible phosphatidylinositol (3,4,5)-trisphosphate (PIP3) binding domain involved in membrane recruitment in response to insulin signalling

conjugated

PhosphoP , Other

mono polymer

heteromer , trimer

HOMOLOGY

interspecies	homolog to rattus Ogt (99.4 pc)
	homolog to murine Ogt (99.6 pc)

Homologene

FAMILY

O-GlcNAc transferase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus
text	expressed in the nucleocytoplasmic compartments

basic FUNCTION	involved in addition of nucleotide-activated sugars directly onto the polypeptide through O-glycosidic linkage with the hydroxyl of serine or threonine
	OGT modification participates in the regulation of CAMK4 activation and function, possibly coordinating nutritional signals with the immune and nervous systems (
	essential (in mouse) for embryonic stem cell viability
	regulates mitotic chromatin dynamics
	catalyzes O-GlcNAc) addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling
	catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins
	function of OGT in hormone signaling
	modification of OGT is involved in many important cellular processes
	essential role of O-GlcNAcylation during early development
	TET2-dependent O-GlcNAcylation of chromatinand the double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription
	catalyzes serine and threonine glycosylation

CELLULAR PROCESS

protein, post translation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate

signaling

signal transduction

protein glycosylation

a component	heterotrimer composed of two 110 kDa and one 78kDa (proteolytic product of the former) subunits
	large proportion of the signaling enzyme OGT is complexed with HCFC1 and this interaction is essential for HCFC1 cleavage
	BAP1 forms a core complex with HCFC1 and OGT that can differentially recruit additional histone-modifying enzymes to regulate gene expression and thereby preserve normal hematopoiesis

INTERACTION

DNA

RNA

small molecule

protein	interacting with THAP1, THAP3 and thus involved in cell proliferation
	HCFC1 is required for stabilizing OGT in the nucleus (interactions of OGT with multiple HCFC1 domains may indicate that OGT has several functions in association with HCFC1)
	TAB1 is modified through OGT on a single site, Ser395 (this modification is induced by IL1 and osmotic stress, known inducers of the MAP3K7 signalling cascade)
	associates with ligand-bound glucocorticoid receptor in a multi-protein repression complex
	interacts with the tetratricopeptide repeat binding site of HSP90AA1
	TET2 and TET3 associate with OGT, an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation)
	OGT associates with TET2 at transcription start sites
	TET1 and TET2 as stable partners of OGT in the nucleus of ESCs
	link between TET1 and OGT activities in regulating CpG island methylation
	POU2F1 integrates metabolic and stress signals via OGT modification to regulate target gene activity
	OGT-modification of CAMK2A is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases
	OGT is not only a major TET3-interacting protein but also regulates TET3 subcellular localization and enzymatic activity
	mediates O-GlcNAcylation of the SNARE protein SNAP29 and regulates autophagy in a nutrient-dependent manner
	OGT modifies and regulates an essential epigenetic tool, RNF2, which may contribute to embryonic stem cells (hESC) pluripotency maintenance and differentiation
	distinct OGT-binding sites in HCFC1 promote proteolysis
	KMT2E protein stability is cooperatively regulated by O-GlcNAc transferase (OGT) and ubiquitin-specific protease 7 (USP7)

cell & other

REGULATION

Other	acetylated
	HSP90AA1 is involved in the regulation of OGT and O-GlcNAc modification

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   homeostasis of OGT cycling is critical to, and its dysregulation is involved in, neurodegenerative diseases constitutional     --over   implicated in major diseases, such as diabetes and its complications and cardiovascular and neurodegenerative diseases constitutional     --over   results in an increase in abnormal chromosomal bridge formation constitutional     --over   increased the inhibitory phosphorylation of cyclin-dependent kinase 1 (CDK1) and reduced the phosphorylation of CDK1 target proteins

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer cycling provides a new target for investigation of these disease mechanisms and for drug development

ANIMAL & CELL MODELS