Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

TERF2

contributors: mct/ - updated : 29-08-2016

HGNC name	telomeric repeat binding factor 2
HGNC id	11729

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	16q22.1      Physical location : 69.389.534 - 69.419.873
Synonym name	TTAGGG repeat-binding factor 2
	telomeric DNA-binding protein
Synonym symbol(s)	TRBF2, TRF2

DNA

TYPE	functioning gene
STRUCTURE	30.34 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005652 10 - 2909 NP_005643 55 500 - - TERF2-S - - - - - in proliferating neural progenitor cells, in cerebellum, cerebral cortex, heart 2011 21903926 short nontelomeric isoform located in the cytoplasm where it sequesters REST, thereby maintaining the expression of neuronal genes acts as part of a unique developmentally regulated molecular switch that plays critical roles in the maintenance and plasticity of neurons truncated TERF2 splice variant enriched in the cytoplasm of neurons, where it plays an important role in the acquisition and maintenance of the differentiated state of these postmitotic cells

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 intestine small intestine     moderately   liver       moderately Endocrine parathyroid       moderately Lymphoid/Immune lymph node       moderately Nervous brain         Homo sapiens Reproductive female system uterus cervix   moderately Respiratory respiratory tract larynx     predominantly Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous glia Homo sapiens

cell lineage
cell lines
fluid/secretion	highly in blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal basic rich domain, and dimerization domain, with DNA binding activity
	a TRFH domain that can prevent activation of the ATM pathway independently from other regions of TERF2
	a central dimerization domain, required to inhibit ATM activation, the key initial step involved in activation of a DNA damage response
	a C-terminal telomere-binding Myb domain , and C-terminal portion of TERF2 Hinge domain is necessary and sufficient to prevent TP53BP1 localization at telomeres

conjugated

PhosphoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to rattus Terf2 (85.1 pc)
	homolog to murine Terf2 (85.5 pc)

intraspecies

homolog to TERF1

Homologene

FAMILY

CATEGORY

regulatory , DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
text	RECQL4 localizes to telomeres and associates with shelterin proteins TERF1 and TERF2

basic FUNCTION	capping factor protecting the chromosome termini from DNA damage checkpoint and from interchromosome fusion
	involved in ATM-independent DNA-damage response
	phosphorylated form may play a key role in both telomere-based and genomic-wide DNA damage signaling responses
	involved in homologous recombination repair of nontelomeric double-strand breaks
	plays an essential role in homologous recombination by facilitating the formation of early recombination intermediates
	playing a role in regulating neuronal differentiation
	protecting against end-to-end fusion of chromosomes
	playing a role in successful progression through the cell division cycle
	an array of TERF2 function as a protein hub and regulate telomeres by recruiting different signaling molecules via a linear sequence code
	maintains telomere integrity by controlling turn over of Holliday Junction at t-loops and at regressed replication forks
	protects telomeric Holliday junctions (HJ) DNA at the t-loop/D-loop from cleavage by endonucleases
	regulates the 5prime exonuclease activity of its binding partner, DCLRE1B that is required for telomere integrity during S phase
	with DCLRE1B, act together with TOP2A to protect the inner portion of telomeres from replicative damage and TERF2-DCLRE1B and various topoisomerases are in balanced amounts at telomeres
	potential role for SIAH1 and TERF2 in TP53-regulated senescence
	TERF1 and TERF2 couple potentially the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences
	preferential recruitment of shelterin complex to areas of the telomere where ss- and ds-DNA are in close proximity, such as the 3prime-telomeric overhang, telomeric DNA bubbles and the D-loop at the base of T-loops
	TERF2IP and TERF2 have the ability to bind to nontelomeric junction sites with similar affinities, raising the question what domain is responsible for the DNA binding ability of TERF2IP
	plays a crucial role in end-protection as it is required to suppress ATM activation and the formation of end-to-end chromosome fusions
	specific ability of TERF2 to protect chromosome ends cannot be explained by a specificity of its DNA binding domain, or by its unique N-terminal basic domain
	TAF7L and TERF2 may actually work together in regulating spermatogenesis

CELLULAR PROCESS	cell cycle, progression
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	negative regulation of telomere maintenance (via telomerase)

PATHWAY

metabolism

signaling

a component	TERF2 complex is primarily involved in telomere protection and contains the TERF2 interacting partner human TERF2IP as well as several factors involved in the DNA damage response
	part of telomere-specific complex, called shelterin, including TERF1, TERF2, TERF2IP, TINF2, POT1
	part of high-molecular-mass telomeric complex, the telosome that contains the six core proteins TERF1, TERF2, TERF2IP, POT1, TINF2 and ACD
	part of Shelterin complex (TERF1, TERF2, POT1, TERF2IP, TINF2, and TPP1)

INTERACTION

DNA	binding to the interstitial telomeric double-stranded TTAGGG repeats

RNA

small molecule

protein	interacting with WRN (recruits WRN for accurate processing of telomeric structures)
	interacting with ERCC4 (increasing ERCC4 activity at telomere, leading to ERCC4-dependent telomere loss)
	functions of TERF1 and TERF2 are linked by TINF2
	coordinated interactions among TINF2, TERF1, and ACD may ensure robust assembly of the telosome, telomere targeting of its subunits, and, ultimately, regulated telomere maintenance
	interacting with NBN and TERF2IP
	interacting with PPP1R10 and MCPH1 via the [Y/F]XL motif
	interacting with PRMT1
	interacting with TERF1, TPP1 and POT1
	interacting with WRN (TERF2 can protect telomeric HJ DNA from WRN activity)
	recruits a number of factors and enzymes required for telomere protection, including DCLRE1B
	functional link between TRF2, the exonuclease activity of DCLRE1B and DNA topology during telomere replication
	binds and stabilizes REST, thereby enforcing neuronal gene silencing
	BRCC3 is a critical factor involved in TERF2-dependent telomere protection suggesting that an important physiological function of the BRCA1 complex is to maintain genomic stability aiding telomere associated proteins in maintaining telomere integrity
	interaction between a "nonprototypic" core promoter recognition factor (TERF2) and an orphan TAF subunit (TAF7L) in mammalian testis-specific gene transcription
	APEX1 associates with TERF2 and POT1 in the cell
	TINF2 binds to TERF1 and TERF2, improving the telomeric localization of TERF2 and its function
	RNF4 nucleosome-targeting is crucially required for the repair of TERF2-depleted dysfunctional telomeres by TP53BP1-mediated non-homologous end joining
	BRIP1 was able to displace TERF2 from the telomeric substrate in an RPA1-dependent manner
	TERF2 specifically interacts with and is sumoylated by PIAS1 in mammalian cells
	PIAS1-mediated sumoylation status of TERF2 serves as a molecular switch that controls the level of TERF2 at telomeres
	interaction of HMGA2 with the key shelterin protein TERF2
	HNRNPH2 is a splicing regulator of TERF2 pre-mRNA that prevents the expression of TERF2-S, a factor implicated in neuronal differentiation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in skin cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed tumor     potential therapeutic application of inhibition of TERF2 function in the treatment of neural tumors

ANIMAL & CELL MODELS