This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs... See more...

Aliases for TERF2 Gene

Aliases for TERF2 Gene

  • Telomeric Repeat Binding Factor 2 2 3 5
  • TRF2 2 3 4
  • Telomeric Repeat-Binding Factor 2 3 4
  • TTAGGG Repeat-Binding Factor 2 3 4
  • Telomeric DNA-Binding Protein 3 4
  • TRBF2 3 4
  • Telomeric Repeat Binding Protein 2 3
  • TERF2 5

External Ids for TERF2 Gene

Previous HGNC Symbols for TERF2 Gene

  • TRBF2

Previous GeneCards Identifiers for TERF2 Gene

  • GC16M060074
  • GC16M069767
  • GC16M069124
  • GC16M069165
  • GC16M067947
  • GC16M069389
  • GC16M055267

Summaries for TERF2 Gene

Entrez Gene Summary for TERF2 Gene

  • This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

GeneCards Summary for TERF2 Gene

TERF2 (Telomeric Repeat Binding Factor 2) is a Protein Coding gene. Diseases associated with TERF2 include Nijmegen Breakage Syndrome and Werner Syndrome. Among its related pathways are Telomere Extension by Telomerase and Meiosis. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein C-terminus binding. An important paralog of this gene is TERF1.

UniProtKB/Swiss-Prot Summary for TERF2 Gene

  • Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.

Gene Wiki entry for TERF2 Gene

Additional gene information for TERF2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TERF2 Gene

Genomics for TERF2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TERF2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TERF2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TERF2

Top Transcription factor binding sites by QIAGEN in the TERF2 gene promoter:
  • AML1a
  • FOXC1
  • GATA-1
  • GATA-2
  • HOXA5
  • Meis-1
  • Meis-1a
  • Meis-1b
  • SEF-1 (1)

Genomic Locations for TERF2 Gene

Genomic Locations for TERF2 Gene
chr16:69,355,567-69,408,571
(GRCh38/hg38)
Size:
53,005 bases
Orientation:
Minus strand
chr16:69,389,464-69,442,474
(GRCh37/hg19)
Size:
53,011 bases
Orientation:
Minus strand

Genomic View for TERF2 Gene

Genes around TERF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TERF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TERF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TERF2 Gene

Proteins for TERF2 Gene

  • Protein details for TERF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15554-TERF2_HUMAN
    Recommended name:
    Telomeric repeat-binding factor 2
    Protein Accession:
    Q15554

    Protein attributes for TERF2 Gene

    Size:
    542 amino acids
    Molecular mass:
    59594 Da
    Quaternary structure:
    • Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts with TERF2IP. Interacts with NBN. Interacts with SLX4/BTBD12. Interacts with DCLRE1B/Apollo and TERF2IP/RAP1; the interaction is direct.
    SequenceCaution:
    • Sequence=AAB81135.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB81135.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={ECO:0000305}; Sequence=AAH24890.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TERF2 Gene

    Alternative splice isoforms for TERF2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TERF2 Gene

Post-translational modifications for TERF2 Gene

  • Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites.
  • Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres.
  • Ubiquitination at Lys335
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TERF2 Gene

Domains & Families for TERF2 Gene

Gene Families for TERF2 Gene

Protein Domains for TERF2 Gene

Suggested Antigen Peptide Sequences for TERF2 Gene

GenScript: Design optimal peptide antigens:
  • Telomeric DNA-binding protein (TERF2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q15554

UniProtKB/Swiss-Prot:

TERF2_HUMAN :
  • The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.
Domain:
  • The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.
  • The HTH domain is an independent structural unit and mediates binding to telomeric DNA.
genes like me logo Genes that share domains with TERF2: view

Function for TERF2 Gene

Molecular function for TERF2 Gene

UniProtKB/Swiss-Prot Function:
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.

Phenotypes From GWAS Catalog for TERF2 Gene

Gene Ontology (GO) - Molecular Function for TERF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0003691 double-stranded telomeric DNA binding IBA,ISS 9326950
GO:0003720 contributes_to telomerase activity IBA,IDA 23685356
GO:0005515 protein binding IPI 10984620
GO:0008022 protein C-terminus binding IPI 12181313
genes like me logo Genes that share ontologies with TERF2: view
genes like me logo Genes that share phenotypes with TERF2: view

Animal Models for TERF2 Gene

MGI Knock Outs for TERF2:

Animal Model Products

CRISPR Products

miRNA for TERF2 Gene

miRTarBase miRNAs that target TERF2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TERF2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TERF2 Gene

Localization for TERF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TERF2 Gene

Nucleus. Chromosome, telomere. Note=Colocalizes with telomeric DNA in interphase cells and is located at chromosome ends during metaphase.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TERF2 gene
Compartment Confidence
nucleus 5
cytosol 2
golgi apparatus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TERF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000781 chromosome, telomeric region IEA,IDA 12768206
GO:0000783 nuclear telomere cap complex IDA 15181449
GO:0000784 nuclear chromosome, telomeric region IEA,IDA 15109494
GO:0005634 nucleus IEA,IDA 17055345
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with TERF2: view

Pathways & Interactions for TERF2 Gene

genes like me logo Genes that share pathways with TERF2: view

Pathways by source for TERF2 Gene

2 Qiagen pathways for TERF2 Gene
  • Telomerase Components in Cell Signaling
  • Telomere Extension by Telomerase
1 Cell Signaling Technology pathway for TERF2 Gene

Gene Ontology (GO) - Biological Process for TERF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000723 telomere maintenance IEA,IMP 20655466
GO:0006278 RNA-dependent DNA biosynthetic process IEA --
GO:0007049 cell cycle IEA --
GO:0010628 positive regulation of gene expression IMP 11927518
GO:0010629 negative regulation of gene expression IMP 11927518
genes like me logo Genes that share ontologies with TERF2: view

No data available for SIGNOR curated interactions for TERF2 Gene

Drugs & Compounds for TERF2 Gene

(1) Drugs for TERF2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(6) Additional Compounds for TERF2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TERF2: view

Transcripts for TERF2 Gene

mRNA/cDNA for TERF2 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TERF2

Alternative Splicing Database (ASD) splice patterns (SP) for TERF2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10
SP1: - -
SP2:
SP3: -

Relevant External Links for TERF2 Gene

GeneLoc Exon Structure for
TERF2

Expression for TERF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TERF2 Gene

Protein differential expression in normal tissues from HIPED for TERF2 Gene

This gene is overexpressed in Plasma (23.2) and Blymphocyte (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TERF2 Gene



Protein tissue co-expression partners for TERF2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TERF2

SOURCE GeneReport for Unigene cluster for TERF2 Gene:

Hs.63335

mRNA Expression by UniProt/SwissProt for TERF2 Gene:

Q15554-TERF2_HUMAN
Tissue specificity: Ubiquitous. Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes.

Evidence on tissue expression from TISSUES for TERF2 Gene

  • Liver(4.5)
  • Adrenal gland(4.3)
  • Blood(2.8)
  • Nervous system(2.8)
  • Muscle(2.8)
  • Heart(2.7)
  • Kidney(2.5)
  • Intestine(2.5)
  • Lung(2.2)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with TERF2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TERF2 Gene

Orthologs for TERF2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TERF2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TERF2 30 31
  • 98.8 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TERF2 30 31
  • 92.87 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TERF2 30 31
  • 91.13 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Terf2 30 17 31
  • 87.66 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Terf2 30
  • 87.37 (n)
Oppossum
(Monodelphis domestica)
Mammalia TERF2 31
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TERF2 31
  • 73 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TERF2 30 31
  • 64.4 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TERF2 31
  • 25 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia terf2 30
  • 53.24 (n)
Zebrafish
(Danio rerio)
Actinopterygii terfa 30 31
  • 47.11 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.5936 31
  • 24 (a)
OneToMany
Species where no ortholog for TERF2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TERF2 Gene

ENSEMBL:
Gene Tree for TERF2 (if available)
TreeFam:
Gene Tree for TERF2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TERF2: view image

Paralogs for TERF2 Gene

Paralogs for TERF2 Gene

(1) SIMAP similar genes for TERF2 Gene using alignment to 9 proteins:

  • TERF2_HUMAN
  • H3BR06_HUMAN
  • H3BR37_HUMAN
  • H3BTA7_HUMAN
  • J3KSJ9_HUMAN
  • J3KSZ6_HUMAN
  • J3KTN8_HUMAN
  • U3KQ35_HUMAN
  • V9GYM1_HUMAN
genes like me logo Genes that share paralogs with TERF2: view

Variants for TERF2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TERF2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
712847 Benign: not provided 69,366,892(-) G/C MISSENSE_VARIANT
714711 Benign: not provided 69,367,182(-) G/T MISSENSE_VARIANT
790710 Benign: not provided 69,368,402(-) C/T SYNONYMOUS_VARIANT
rs35874485 - p.Ser455Gly

Additional dbSNP identifiers (rs#s) for TERF2 Gene

Structural Variations from Database of Genomic Variants (DGV) for TERF2 Gene

Variant ID Type Subtype PubMed ID
esv3329158 CNV insertion 20981092
esv3388367 CNV insertion 20981092
nsv509629 CNV insertion 20534489
nsv974826 CNV duplication 23825009

Variation tolerance for TERF2 Gene

Gene Damage Index Score: 2.11; 38.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TERF2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TERF2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TERF2 Gene

Disorders for TERF2 Gene

MalaCards: The human disease database

(9) MalaCards diseases for TERF2 Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TERF2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TERF2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TERF2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TERF2 Gene

Publications for TERF2 Gene

  1. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. (PMID: 9326950) Broccoli D … de Lange T (Nature genetics 1997) 2 3 4 23
  2. Arginine methylation regulates telomere length and stability. (PMID: 19596784) Mitchell TR … Zhu XD (Molecular and cellular biology 2009) 3 4 23
  3. Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis. (PMID: 19766477) Varadi V … Försti A (European journal of cancer (Oxford, England : 1990) 2009) 3 23 41
  4. Polymorphisms in telomere maintenance genes and risk of lung cancer. (PMID: 19773453) Choi JE … Park JY (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2009) 3 23 41
  5. Genetic variation in five genes important in telomere biology and risk for breast cancer. (PMID: 17848914) Savage SA … Garcia-Closas M (British journal of cancer 2007) 3 23 41

Products for TERF2 Gene

  • Signalway ELISA kits for TERF2

Sources for TERF2 Gene