Human Gene TERF2 (uc002exd.4) Description and Page Index
Description: Homo sapiens telomeric repeat binding factor 2 (TERF2), mRNA. RefSeq Summary (NM_005652): 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]. CCDS Note: The coding region has been updated to extend the N-terminus to one that is more supported by the available transcript and conservation data. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF002999.1, SRR1803611.49458.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000254942.8/ ENSP00000254942.3 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chr16:69,389,464-69,419,891 Size: 30,428 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr16:69,390,801-69,419,748 Size: 28,948 Coding Exon Count: 10
ID:TERF2_HUMAN DESCRIPTION: RecName: Full=Telomeric repeat-binding factor 2; AltName: Full=TTAGGG repeat-binding factor 2; AltName: Full=Telomeric DNA-binding protein; 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. SUBUNIT: 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. INTERACTION: P54132:BLM; NbExp=8; IntAct=EBI-706637, EBI-621372; Q9H816:DCLRE1B; NbExp=6; IntAct=EBI-706637, EBI-3508943; Q9NUX5:POT1; NbExp=3; IntAct=EBI-706637, EBI-752420; Q8IY92:SLX4; NbExp=5; IntAct=EBI-706637, EBI-2370740; Q9NYB0:TERF2IP; NbExp=5; IntAct=EBI-706637, EBI-750109; Q9BSI4-3:TINF2; NbExp=4; IntAct=EBI-706637, EBI-717418; Q14191:WRN; NbExp=8; IntAct=EBI-706637, EBI-368417; SUBCELLULAR LOCATION: Nucleus. Chromosome, telomere. Note=Colocalizes with telomeric DNA in interphase cells and is located at chromosome ends during metaphase. TISSUE SPECIFICITY: Ubiquitous. Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes. DOMAIN: The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2. DOMAIN: The HTH domain is an independent structural unit and mediates binding to telomeric DNA. PTM: Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites. PTM: Methylated by PRMT1 at multiple arginines within the N- terminal Arg-rich region. Methylation may control association with telomeres. SIMILARITY: Contains 1 HTH myb-type DNA-binding domain.
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): TERF2 CDC HuGE Published Literature: TERF2 Positive Disease Associations: anemia, aplastic Related Studies:
anemia, aplastic Savage, S. A. et al. 2006, Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia, Exp Hematol 2006 34(5) 664-71.
It is possible that a common genetic variant in TERF1 is associated with risk for AA but additional studies are required.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15554
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000723 telomere maintenance GO:0006278 RNA-dependent DNA biosynthetic process GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0007049 cell cycle GO:0010628 positive regulation of gene expression GO:0010629 negative regulation of gene expression GO:0016233 telomere capping GO:0031627 telomeric loop formation GO:0031848 protection from non-homologous end joining at telomere GO:0032204 regulation of telomere maintenance GO:0032205 negative regulation of telomere maintenance GO:0032208 negative regulation of telomere maintenance via recombination GO:0032210 regulation of telomere maintenance via telomerase GO:0032211 negative regulation of telomere maintenance via telomerase GO:0032214 negative regulation of telomere maintenance via semi-conservative replication GO:0051000 positive regulation of nitric-oxide synthase activity GO:0061820 telomeric D-loop disassembly GO:0070198 protein localization to chromosome, telomeric region GO:0090398 cellular senescence GO:1903770 negative regulation of beta-galactosidase activity GO:1903824 negative regulation of telomere single strand break repair GO:1904354 negative regulation of telomere capping GO:1904357 negative regulation of telomere maintenance via telomere lengthening GO:1904430 negative regulation of t-circle formation GO:1905778 negative regulation of exonuclease activity GO:2000773 negative regulation of cellular senescence