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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:69,389,464-69,419,891)mRNA (may differ from genome)Protein (542 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  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:
  1. 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. [PubMed 16647572]
    It is possible that a common genetic variant in TERF1 is associated with risk for AA but additional studies are required.

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.18 RPKM in Testis
Total median expression: 211.77 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -72.10143-0.504 Picture PostScript Text
3' UTR -399.471337-0.299 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009057 - Homeodomain-like
IPR017930 - Myb_dom
IPR001005 - SANT/Myb
IPR017357 - Telomere_repeat-bd-1/2
IPR013867 - Telomere_rpt-bd_fac_dimer_dom

Pfam Domains:
PF00249 - Myb-like DNA-binding domain
PF08558 - Telomere repeat binding factor (TRF)
PF13921 - Myb-like DNA-binding domain
PF16772 - Telomeric repeat-binding factor 2 Rap1-binding motif

SCOP Domains:
63600 - Telomeric repeat binding factor (TRF) dimerisation domain
46689 - Homeodomain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1H6P
- X-ray MuPIT

1VF9
- NMR MuPIT

1VFC
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1W0U - X-ray MuPIT 1XG1 - NMR MuPIT 3BU8 - X-ray MuPIT
3BUA - X-ray MuPIT 3K6G - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q15554
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003691 double-stranded telomeric DNA binding
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0019899 enzyme binding
GO:0042162 telomeric DNA binding
GO:0042803 protein homodimerization activity
GO:0044877 macromolecular complex binding
GO:0098505 G-rich strand telomeric DNA binding
GO:0003720 telomerase activity

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

Cellular Component:
GO:0000781 chromosome, telomeric region
GO:0000783 nuclear telomere cap complex
GO:0000784 nuclear chromosome, telomeric region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0016604 nuclear body
GO:0070187 telosome
GO:0030870 Mre11 complex


-  Descriptions from all associated GenBank mRNAs
  AF002999 - Homo sapiens TTAGGG repeat binding factor 2 (hTRF2) mRNA, complete cds.
JD565977 - Sequence 547001 from Patent EP1572962.
JD561556 - Sequence 542580 from Patent EP1572962.
JD091730 - Sequence 72754 from Patent EP1572962.
JD399547 - Sequence 380571 from Patent EP1572962.
JD392755 - Sequence 373779 from Patent EP1572962.
JD280723 - Sequence 261747 from Patent EP1572962.
JD410611 - Sequence 391635 from Patent EP1572962.
JD205224 - Sequence 186248 from Patent EP1572962.
JD084223 - Sequence 65247 from Patent EP1572962.
JD318205 - Sequence 299229 from Patent EP1572962.
JD318206 - Sequence 299230 from Patent EP1572962.
JD203795 - Sequence 184819 from Patent EP1572962.
JD213409 - Sequence 194433 from Patent EP1572962.
JD152366 - Sequence 133390 from Patent EP1572962.
JD258841 - Sequence 239865 from Patent EP1572962.
JD353122 - Sequence 334146 from Patent EP1572962.
JD448681 - Sequence 429705 from Patent EP1572962.
X93512 - H.sapiens mRNA for telomeric DNA binding protein (orf2).
JD093807 - Sequence 74831 from Patent EP1572962.
JD454881 - Sequence 435905 from Patent EP1572962.
JD330435 - Sequence 311459 from Patent EP1572962.
U95970 - Homo sapiens telomeric repeat factor 2 (TRF2) mRNA, partial cds.
BC024890 - Homo sapiens telomeric repeat binding factor 2, mRNA (cDNA clone MGC:17060 IMAGE:4346819), complete cds.
JD506765 - Sequence 487789 from Patent EP1572962.
JD211587 - Sequence 192611 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q15554 (Reactome details) participates in the following event(s):

R-HSA-176700 Incorporation Of Extended And Processed Telomere End Into Higher Order T-Loop And Associated Protein Structure
R-HSA-181450 Incorporation Of Extended And Processed Telomere End Into Associated Protein Structure
R-HSA-171306 Packaging Of Telomere Ends
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-1221632 Meiotic synapsis
R-HSA-157579 Telomere Maintenance
R-HSA-2559583 Cellular Senescence
R-HSA-1500620 Meiosis
R-HSA-73886 Chromosome Maintenance
R-HSA-2262752 Cellular responses to stress
R-HSA-1474165 Reproduction
R-HSA-1640170 Cell Cycle
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: NM_005652, NP_005643, Q15554, TERF2_HUMAN, TRBF2, TRF2, uc002exd.3
UCSC ID: uc002exd.4
RefSeq Accession: NM_005652
Protein: Q15554 (aka TERF2_HUMAN or TRF2_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005652.4
exon count: 10CDS single in 3' UTR: no RNA size: 2996
ORF size: 1503CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3376.00frame shift in genome: no % Coverage: 99.57
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.