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FLASH GENE
Symbol TERF1 contributors: mct/ - updated : 25-04-2017
HGNC name telomeric repeat binding factor (NIMA-interacting) 1
HGNC id 11728
Location 8q21.11      Physical location : 73.921.096 - 73.959.987
Synonym name
  • telomeric repeat binding factor 1
  • TTAGGG repeats binding factor 1
  • NIMA-interacting protein 2
  • telomeric protein Pin2/TRF1
  • shelterin complex
  • Synonym symbol(s) TRF1, TRBF1, TRF, PIN2, t-TRF1, FLJ41416, hTRF1-AS
    DNA
    TYPE functioning gene
    STRUCTURE 38.89 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure DNA binding sites
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 2960 50.1 439 brain 2003 12944479
  • isoform 1
  • 9 splicing 2900 48.1 419 brain 2003 12944479
  • lacking an alternate in-frame exon compared to variant 1
  • isoform 2
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately
     pancreas exocrine   moderately
    Endocrineparathyroid   highly
    Hearing/Equilibriumear   highly
    Nervousnerve   moderately
    Reproductivefemale systemuterus  moderately
     male systemprostate  highly
     male systemtestis  moderately
    Respiratorylung   moderately
    Urinarykidney   moderately
    Visualeye   moderately
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    cell cycle     cell cycle
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N terminal acidic rich domain
  • a dimerization domain in the center
  • a TRF homology domain interacting with a minimal 20-AA sequence of PINX1 via hydrophilic and hydrophobic interactions
  • a C-terminal HTH Myb-related DNA binding motif
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to rattus Terf1 (67.9 pc)
    homolog to murine Terf1 (67.5 pc)
    intraspecies homolog to telomeric Myb protein
    homolog to TERF2
    Homologene
    FAMILY
    CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nuclear envelope,matrix attachement regions
    text
  • co-localization of ZSCAN4 and TERF1 to the nucleus
  • is exclusively located at telomeres both under normal conditions, as well as under extreme telomere shortening
  • basic FUNCTION
  • suppressor of telomere elongation involved in the feedback mechanism that stabilizes telomere length
  • essential transacting factor for de novo telomere formation
  • involved in the control of the lifespan of cells and establishment of immortality through the regulation of telomere function and telomere maintenance when anchored to the nuclear matrix
  • having an essential function independent of telomere length regulation
  • negatively regulating telomere length and also playing a critical role in cell cycle checkpoint control
  • double-stranded DNA-binding protein known to regulate telomere length by not only protecting telomere but also blocking the access of telomerase to telomere in cis
  • able to specifically recognize telomeric binding sites located within nucleosomes, forming a ternary complex
  • specifically recognizes nucleosomal binding sites and alters nucleosome structure
  • bind double-stranded telomeric DNA, and it negatively regulates telomere elongation
  • regulates telomere length and function by at least two mechanisms, in one acts through the recruiting/tethering of other shelterin components to telomeres, and in the other TERF1 seems to play a more direct role
  • key regulator in telomere maintenance
  • acts as a negative regulator of telomere length by controlling XPF activity at telomeres
  • like TRF2, negatively regulates telomere length by controlling the action of the XPF nuclease at telomeres and has a unique role in the mitotic spindle checkpoint
  • controls telomere length and mitotic fidelity in epithelial homeostasis
  • post-translational modifications of TERF1 play important roles in modulating telomere length homeostasis by determining the abundance of TERF1 at telomeres
  • specifically inducing mobility of telomeric nucleosomes and inducing compaction of telomeric DNA only in the presence of a nucleosome
  • recruits PINX1 to telomeres, providing a crucial link between TERF1 and inhibition of telomere elongation by telomerase to help maintain telomere homeostasis
  • 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
  • is necessary for both induction and maintenance of pluripotency, and TERF1 is a direct transcriptional target of POU5F1
  • TERF1 functions likely as a negative regulator of telomere length by controlling the access of telomerase to telomeres
  • telomere-binding protein, that is important for telomere protection and homeostasis
  • TERF1 has been established as a telomeric protein that negatively regulates telomere elongation by telomerase and promotes efficient DNA replication at telomeres
  • TERF1 regulates the rigidity of the microtubule-kinetochore attachment, contributing to proper chromosome segregation and the maintenance of genomic integrity
  • is one of the components of shelterin and has been shown to be essential for telomere protection
  • CELLULAR PROCESS nucleotide, replication
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    TERT, a catalytic component of telomerase, plays dual roles in the TERF1 steady state pathway
    a component
  • TERF1 complex contains the TERF1 interacting partner, TINF2, as well as PAK1IP1 and POT1 and regulates telomere-length homeostasis
  • part of telomere-specific complex, called shelterin, including TERF1, TERF2, TERF2IP, TINF2, POT1
  • found in a complex with POT1, TINF2 and TNKS1
  • ADP-ribolsylation
  • 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, specifically the long (TTAGGG)(n) double-stranded telomeric DNA repeats
    RNA
    small molecule
    protein
  • interacting with PINX1, TNKS, TNKS2, TINF2 (implicated in the regulation of telomerase-dependent telomere length maintenance)
  • coordinated interactions among TINF2, ACD, and TERF2 may ensure robust assembly of the telosome, telomere targeting of its subunits, and, ultimately, regulated telomere maintenance
  • interacting with MYC
  • interacting with ATM, TNKS2, NEK2 and MAPRE1
  • GNL3L binds TERF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TERF1, preventing promyelocytic leukemia body recruitment of telomere-bound TERF1)
  • interacting with PIN1 (PIN1 inhibition renders TERF1 resistant to protein degradation, enhances TERF1 binding to telomeres, and leads to gradual telomere loss in cells)
  • with components of the mitotic spindle, including the mitotic kinase NIMA and the spindle regulator MAD1 and interact with microtubules and control microtubule polymerization
  • interacting with TPP1, TERF2 and POT1
  • PINX1-TERF1 interaction may play a role in the stabilization of telomeres in cells
  • TERF1-PINX1 interaction is required not only for targeting PINX1 to telomeres but also for PINX1 to prevent telomere elongation in cells
  • RECQL4 localizes to telomeres and associates with shelterin proteins TERF1 and TERF2
  • TERF1 dimerization is actively and oppositely regulated by GNL3 and GNL3L extrachromosomally
  • one function of PINX1 is likely to stabilize TERF1 during mitosis, perhaps to promote transition into M phase of the cell cycle
  • GNL3 prevents telomere damage by promoting PML-IV recruitment to SUMOylated TERF1
  • BTRC is a novel TERF1-associating protein
  • RTEL1 interacts with the shelterin protein TERF1, providing a potential recruitment mechanism of RTEL1 to telomeres
  • U2AF2 is an essential pre-mRNA splicing factor, and a novel TERF1-interacting protein
  • PINX1 may maintain telomere integrity by regulating TERF1 stability and TERT may act as both a positive and a negative regulator of TERF1 homeostasis in a PINX1-dependent manner
  • TINF2 binds to TERF1 and TERF2, improving the telomeric localization of TERF2 and its function
  • is required for the centromeric function of AURKB, which ensures proper chromosome segregation
  • physical interaction between TERF1 and AFAP1L2 proteins (this finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development)
  • interaction of ZSCAN4 with TERF1 functions in regulation of telomere elongation in ESC
  • overexpression of TERF1 in aging endothelial cells (EC) reduced telomere-associated DNA damage foci and reduced expression levels of CCL2
  • functional interplay between STAG1 and TERF1 in telomeric DNA binding and DNA-DNA pairing
  • cell & other
    REGULATION
    inhibited by TNKS
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer (to maintain long telomeres)
    constitutional     --over  
    results in aberrant mitotic spindles, demonstrating a specific role for TERF1 in mitosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS