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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
    Physical map
    LOC389667 8 similar to tropomyosin 4 SULF1 8q13.1 similar to tropomyosin 4 SLCO5A1 8q13.2 solute carrier family 21 (organic anion transporter), member 15 LOC392230 8 similar to BAG-family molecular chaperone regulator-4 (Silencer of death domains) PRDM14 8p21-p12 PR domain containing 14 LOC346990 8q13.2 similar to H2A histone family, member Z NCOA2 8q13.1 nuclear receptor coactivator 2 LOC392231 8 similar to basic transcription factor 3 TRAM1 8q13.1 translocation associated membrane protein 1 CGI-83 LOC389668 8 similar to hypothetical protein FLJ10307 EYA1 8q13.3 eyes absent homolog 1 (Drosophila) MSC 8q21.1-q21.2 musculin (activated B-cell factor-1) TRPA1 8q13 transient receptor potential cation channel, subfamily A, member 1 LOC392232 8 similar to ankyrin-like protein 1; ankyrin-like with transmembrane domains 1 KCNB2 8q13.2 potassium voltage-gated channel, Shab-related subfamily, member 2 TERF1 8q13 telomeric repeat binding factor (NIMA-interacting) 1 RPESP 8q13.3 RPE-spondin LOC392233 8 similar to Hspcb protein LOC389669 8 LOC389669 RPL7 8q12-q22 ribosomal protein L7 RDH10 8q13.3 retinol dehydrogenase 10 (all-trans) STAU2 8q13-q21.1 staufen, RNA binding protein, homolog 2 (Drosophila) FLJ11011 8q13.3 hypothetical protein FLJ11011 TCEB1 8q13-q21 transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C) FLJ20533 8q13.3 hypothetical protein FLJ20533 LOC157793 8q13.3 similar to destrin - pig LY96 8q13.3 lymphocyte antigen 96 JPH1 8q21 junctophilin 1 GDAP1 8q13.3-q21 ganglioside-induced differentiation-associated protein 1 LOC286157 8q13.3 similar to mCBP PI15 8q13.3 protease inhibitor 15 LOC83690 8q13.3 CocoaCrisp LOC389670 8 hypothetical gene supported by BC062758 LOC392234 8 similar to Pyruvate kinase, M2 isozyme HNF4G 8q21.3-q22.1 hepatocyte nuclear factor 4, gamma MRPL9P1 8q21.11 mitochondrial ribosomal protein L9 pseudogene ZFH4 8q13.3 mitochondrial ribosomal protein L9 pseudogene PXMP3 8q21.1 peroxisomal membrane protein 3, 35kDa (Zellweger syndrome)
    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