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Symbol TERF2 contributors: mct/ - updated : 29-08-2016
HGNC name telomeric repeat binding factor 2
HGNC id 11729
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
    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
    Physical map
    LOC339065 16q22.1 similar to putative membrane-bound dipeptidase-2 DDX28 16q22.2 DEAD (Asp-Glu-Ala-Asp) box polypeptide 28 FLJ20399 16q22.1 hypothetical protein FLJ20399 NFATC3 16q22.1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 FLJ21918 16q22.1 hypothetical protein FLJ21918 LYPLA3 16q22.1 lysophospholipase 3 (lysosomal phospholipase A2) SLC7A6 16q22.1 solute carrier family 7 (cationic amino acid transporter, y+ system), member 6 FLJ13291 16q22.1 hypothetical protein FLJ13291 FLJ10640 16q22.1 hypothetical protein FLJ10640 FLJ22593 16q22.1 hypothetical protein FLJ22593 SMPD3 16q22.2 sphingomyelin phosphodiesterase 3, neutral membrane (neutral sphingomyelinase II) ZFP90 16q22.1 zinc finger protein 90 homolog (mouse) CDH3 16q22.1 cadherin 3, type 1, P-cadherin (placental) CDH1 16q22.1 cadherin 1, type 1, E-cadherin (epithelial) FLJ12331 16q22.1 hypothetical protein FLJ12331 HAS3 16q22.1 hyaluronan synthase 3 FLJ20400 16q22.1 CTF8, chromosome transmission fidelity factor 8 homolog (S. cerevisiae) CIRH1A 16q22.1 cirrhosis, autosomal recessive 1A (cirhin) SNTB2 16q22-q23 syntrophin, beta 2 (dystrophin-associated protein A1, 59kDa, basic component 2) VPS4A 16q23.1 vacuolar protein sorting 4A (yeast) COG8 16q22.1 component of oligomeric golgi complex 8 PDF 16q22.1 peptide deformylase-like protein CGI-37 16q22.1 comparative gene identification transcript 37 MGC23911 16q22.1 hypothetical protein MGC23911 TERF2 16q22.1 telomeric repeat binding factor 2 CYB5-M 16q22.1 cytochrome b5 outer mitochondrial membrane precursor NFAT5 16q22.1 nuclear factor of activated T-cells 5, tonicity-responsive NQO1 16q12-q22 NAD(P)H dehydrogenase, quinone 1 NOB1P 16q22.3 likely ortholog of mouse nin one binding protein LOC388285 16 hypothetical gene supported by U89867; NM_007363 WWP2 16q22.1 Nedd-4-like ubiquitin-protein ligase LOC348174 16q22.1 secretory protein LOC348174 LOC390737 16 similar to MGC9515 protein LOC283970 16q22.1 hypothetical protein LOC283970 PDPR 16q22.1 pyruvate dehydrogenase phosphatase regulatory subunit MGC34761 16q22.1 hypothetical protein MGC34761 LOC388286 16 hypothetical gene supported by AF395444; NM_014006 MTR3 16q22.1 homolog of yeast mRNA transport regulator 3 AARS 16q22.1 alanyl-tRNA synthetase DDX19 16q22.1 DEAD (Asp-Glu-Ala-As) box polypeptide 19 FLJ11126 16q22.1 hypothetical protein FLJ11126 SIAT4B 16q22.3 sialyltransferase 4B (beta-galactoside alpha-2,3-sialyltransferase) FUK 16q22.1 fucokinase COG4 16q22.3 component of oligomeric golgi complex 4 SF3B3 16q22.1 splicing factor 3b, subunit 3, 130kDa
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2909 55 500 - -
    - - - - - 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
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  moderately
     liver   moderately
    Endocrineparathyroid   moderately
    Lymphoid/Immunelymph node   moderately
    Nervousbrain     Homo sapiens
    Reproductivefemale systemuteruscervix moderately
    Respiratoryrespiratory tractlarynx  predominantly
    Visualeye   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    SystemCellPubmedSpeciesStageRna symbol
    Nervousglia Homo sapiens
    cell lineage
    cell lines
    fluid/secretion highly in blood
    at STAGE
  • 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
    interspecies homolog to rattus Terf2 (85.1 pc)
    homolog to murine Terf2 (85.5 pc)
    intraspecies homolog to TERF1
    CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
  • 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
    text negative regulation of telomere maintenance (via telomerase)
    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)
    DNA binding to the interstitial telomeric double-stranded TTAGGG repeats
    small molecule
  • 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
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in skin cancer
    Variant & Polymorphism
    Candidate gene
    Therapy target
    potential therapeutic application of inhibition of TERF2 function in the treatment of neural tumors