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FLASH GENE

Symbol

TET2

contributors: mct/ - updated : 31-05-2019

HGNC name	tet oncogene family member 2
HGNC id	25941

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	4q24      Physical location : 106.067.942 - 106.200.958
Synonym name	KIAA1546 protein
	ten-eleven translocation 2
Synonym symbol(s)	MGC125715, KIAA1546, FLJ20032, MDS
EC.number	1.14.11.n2

DNA

TYPE	functioning gene
STRUCTURE	133.02 kb     11 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001127208 11 - 9677 NP_001120680 - 2002 - 2009 19262601 NM_017628 3 - 9215 NP_060098 - 1165 - 2009 19262601

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 tongue     highly Hearing/Equilibrium ear       highly Nervous brain       highly Homo sapiens Reproductive female system breast mammary gland   highly

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Homo sapiens Blood/Hematopoietic mature hematopoietic Homo sapiens Lymphoid/Immune macrophage Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY

TET family

CATEGORY

DNA associated , tumor suppressor

SUBCELLULAR LOCALIZATION

basic FUNCTION	has an important role in hematopoiesis and in the pathogenesis of myelodysplasia and myeloid malignancies
	implicated in myeloproliferative neoplasm and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells
	PARP1 and TET2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming
	enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC)
	has a critical role in survival and hematopoietic stem cell homeostasis
	implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated
	is critical for the full activation of >50 genes that become upregulated during pre-B cell to macrophage transdifferentiation
	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
	TET2, TET3 are required for 5-hydroxymethylcytosine (5hmC) enrichment at enhancers, a condition necessary for expression of adjacent genes
	neuronal TET2 is positively involved in the regulation of cell survival
	in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression
	molecular circuitry in which opposing functions of TET1 and TET2 control acquisition of alternative pluripotent states
	TET1, TET2, TET3 influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling
	TET2 plays a role in the iron and heme metabolism in erythroblasts
	distinct roles for TET2 and TET3 in human erythropoiesis
	TET2-mediated DNA demethylation promotes the expression of ferroportin and erythroferrone against oxidative stress
	protective role of TET2 in erythroid iron homeostasis against oxidative stress and erythropoiesis
	TET2 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation, and also affects transcription by recruiting histone modifiers
	TET2 is an important regulator of CD8+ T cell fate decisions
	TET1 and TET2 play a critical role in maintaining bone marrow MSCs and bone homeostasis through demethylation of P2RX7 to control exosome and miRNA release
	TET2 was found to be a promoter of both osteogenesis and adipogenesis
	TET2 and TET3 are guardians of Treg cell stability and immune homeostasis
	promotes de-methylation of DNA by catalyzing conversion of methylation to 5-hydroxymethylation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	TET2–OGT complex might be involved in transcriptional activation in embryonic stem cells
	CXXC5 forms a complex with NANOG, POU5F1, TET1, and TET2 and facilitates their proper recruitment to regulatory regions of pluripotency and TET genes in ESCs to positively regulate their transcription

INTERACTION

DNA

RNA

small molecule

protein	TET2 helps CEBPA rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages
	TET2 directly binds to the methylated promoters of its target genes, resulting in hydroxylation and correlating with the genes strong activation
	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
	PRDM14 maintains pluripotency of embryonic stem cells through TET1, TET2-mediated active DNA demethylation
	Vitamin C potentiates TET activity and acts through TET2/TET3 to increase the stability of FOXP3 expression in TGFB1-induced T reg cells
	ZNF281 interacts with TET1, but not TET2
	dual role for TET2 in promoting and inhibiting HSC differentiation, the loss of which, along with DNMT3A, obstructs differentiation, leading to transformation
	histone H3K4 methyltransferase SETD1A is differentially recruited between macrophages (MACs) and osteoclasts (OCs) in a TET2-dependent manner
	CXXC5 binds to the chromatin and is enriched at promoters and enhancers of TET1, TET2, and pluripotency genes
	STAT3 regulated IFI44L expression and interacted with TET2 which induced DNA demethylation of IFI44L promoter

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23) tumoral     --low   lower in myelodysplasia cells regardless of mutational status, raising the possibility of nonmutational TET2 dysregulation in cases lacking mutations tumoral somatic mutation       is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers tumoral somatic mutation       affect global methylation in chronic myelomonocytic leukemia but most of the changes are likely to be outside gene promoters constitutional somatic mutation       present in normal elderly individuals with myeloid skewing and are associated with epigenetic alterations tumoral germinal mutation       in B cells of patients affected by angioimmunoblastic T-cell lymphoma (AITL) constitutional     --low   results in hypermethylation of promoter CpG islands (CGIs) and enhancers in loci largely overlapping with those induced by oxidative stress (OS)

Susceptibility

to early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD), late-onset Alzheimer’s disease (LOAD), and ALS (amyotrophic lateral sclerosis)

Variant & Polymorphism other	loss of TET2 function confers risk for EOAD, LOAD, FTD, and ALS, and pecifically, in aggregate, both coding and non-coding qualifying rare variation in TET2 is associated with approximately a 2-fold risk increase across diverse populations of individuals with AD, FTD, and ALS

Candidate gene
Marker
Therapy target	Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation

ANIMAL & CELL MODELS

reducing Tet2 in mouse hippocampus leads to reduced neurogenesis and impaired memory,58 consistent with its role in promoting adult neurogenesis in mice