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Protein

Telomeric repeat-binding factor 2

Gene

Terf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi511 – 536H-T-H motifPROSITE-ProRule annotationAdd BLAST26

GO - Molecular functioni

  • double-stranded telomeric DNA binding Source: BHF-UCL
  • enzyme binding Source: MGI
  • G-rich strand telomeric DNA binding Source: MGI
  • protein-containing complex binding Source: BHF-UCL
  • protein C-terminus binding Source: MGI
  • protein homodimerization activity Source: BHF-UCL
  • telomeric DNA binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle

Enzyme and pathway databases

ReactomeiR-MMU-171306 Packaging Of Telomere Ends
R-MMU-2559586 DNA Damage/Telomere Stress Induced Senescence

Names & Taxonomyi

Protein namesi
Recommended name:
Telomeric repeat-binding factor 2
Alternative name(s):
TTAGGG repeat-binding factor 2
Telomeric DNA-binding protein
Gene namesi
Name:Terf2
Synonyms:Trf2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1195972 Terf2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi165F → A: Abolishes interaction with DCLRE1B/Apollo, leading to activate the ATM signaling pathway. 1 Publication1
Mutagenesisi335 – 336AF → SS: Abolishes interaction with TERF2IP/RAP1 but does not affect protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001971321 – 541Telomeric repeat-binding factor 2Add BLAST541

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62Asymmetric dimethylarginine; by PRMT1By similarity1
Modified residuei63Omega-N-methylarginineBy similarity1
Modified residuei233Phosphothreonine; by ATMBy similarity1
Cross-linki290Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki337Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki355Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei364PhosphoserineCombined sources1
Modified residuei366PhosphoserineCombined sources1
Modified residuei367PhosphoserineCombined sources1
Cross-linki371Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki377Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO35144
MaxQBiO35144
PaxDbiO35144
PeptideAtlasiO35144
PRIDEiO35144

PTM databases

iPTMnetiO35144
PhosphoSitePlusiO35144

Expressioni

Gene expression databases

BgeeiENSMUSG00000031921 Expressed in 280 organ(s), highest expression level in thymus
CleanExiMM_TERF2
ExpressionAtlasiO35144 baseline and differential
GenevisibleiO35144 MM

Interactioni

Subunit structurei

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; the interaction is direct (By similarity). Interacts with TERF2IP/RAP1; the interaction is direct.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dna2Q6ZQJ54EBI-6919263,EBI-6919222

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204117, 8 interactors
ComplexPortaliCPX-153 Shelterin complex
CPX-498 Slx4-Terf2 complex
IntActiO35144, 8 interactors
MINTiO35144
STRINGi10090.ENSMUSP00000118759

Structurei

3D structure databases

ProteinModelPortaliO35144
SMRiO35144
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini483 – 540HTH myb-typePROSITE-ProRule annotationAdd BLAST58

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni87 – 290TRFH dimerizationAdd BLAST204

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi373 – 377Nuclear localization signalSequence analysis5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi58 – 75Arg-rich (basic)Add BLAST18

Domaini

The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.By similarity
The HTH domain is an independent structural unit and mediates binding to telomeric DNA.By similarity

Phylogenomic databases

eggNOGiENOG410IJXM Eukaryota
ENOG4111KJ3 LUCA
GeneTreeiENSGT00530000063796
HOGENOMiHOG000154547
HOVERGENiHBG108560
InParanoidiO35144
KOiK11111
OrthoDBiEOG091G04CC
PhylomeDBiO35144

Family and domain databases

CDDicd11654 TRF2_RBM, 1 hit
Gene3Di1.25.40.210, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017930 Myb_dom
IPR001005 SANT/Myb
IPR013867 Telomere_rpt-bd_fac_dimer_dom
IPR036507 Telomere_rpt-bd_fac_dimer_sf
IPR017357 TERF1/2
IPR030657 TERF2
IPR031902 TERF2_RBM
PANTHERiPTHR21717:SF13 PTHR21717:SF13, 1 hit
PfamiView protein in Pfam
PF00249 Myb_DNA-binding, 1 hit
PF16772 TERF2_RBM, 1 hit
PF08558 TRF, 1 hit
PIRSFiPIRSF038016 Telomere_bd-1_Pin2, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014243 Telomere_repeat-bd_fac_dimer, 1 hit
SMARTiView protein in SMART
SM00717 SANT, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF63600 SSF63600, 1 hit
PROSITEiView protein in PROSITE
PS51294 HTH_MYB, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O35144-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAAGAGTAGP ASGPGVVRDP MASQPRKRPS REGGEGGEGE RRSNTMAGGG
60 70 80 90 100
GSSDSSGRAA SRRASRSGGR ARRGRHEPGL GGAAERGAGE ARLEEAVNRW
110 120 130 140 150
VLKFYFHEAL RAFRSSRYRD FRQIRDIMQA LLVRPLGKEH TVSRLLRVMQ
160 170 180 190 200
CLSRIEEGEN LDCSFDMEAE LTPLESAINV LEMIKTEFTL TDSMVESSRK
210 220 230 240 250
LVKEAAVIIC IKNKEFEKAS KILKKYMSKD PTTQKLRTDL LNIIREKNLA
260 270 280 290 300
HPVIQNFSYE VFQQKMLRFL ESHLDDTEPY LLTMAKKALK SESAASSTMR
310 320 330 340 350
EEKHPEPVEK PLREPPSRQP QNPPATIGIR TLKAAFKALS TAQDSEAAFA
360 370 380 390 400
KLDQKDLVLA NLASPSSPAH KHKRPRKDEH ESAAPAEGEG GSDRQPRNSP
410 420 430 440 450
MTISRLLLEE DSQSTEPSPG LNSSHKAMSA SKPRALNQPH PGEKKPKASK
460 470 480 490 500
DKWNSPNGLE EKEVWLEEDQ LFEVQAPGED RSSSLTRKQK WTIEESEWVK
510 520 530 540
DGVRKYGEGN WAAISKSYPF VNRTAVMIKD RWRTMKKLGM N
Length:541
Mass (Da):60,263
Last modified:July 27, 2011 - v3
Checksum:i2788F7322506182C
GO
Isoform 2 (identifier: O35144-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     448-541: ASKDKWNSPN...WRTMKKLGMN → YEDLLCRSLGAGWRAWLGLVLLP

Show »
Length:470
Mass (Da):51,828
Checksum:i803C8DD1B0DDFCB0
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3YZ08D3YZ08_MOUSE
Telomeric repeat-binding factor
Terf2
540Annotation score:
E9QM06E9QM06_MOUSE
Telomeric repeat-binding factor
Terf2
476Annotation score:
F6VIR4F6VIR4_MOUSE
Telomeric repeat-binding factor 2
Terf2
179Annotation score:

Sequence cautioni

The sequence AAB81136 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC33784 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti317Missing in AAB81136 (PubMed:9326950).Curated1
Sequence conflicti393D → S in AAB81136 (PubMed:9326950).Curated1
Sequence conflicti426K → E in AAH46284 (PubMed:15489334).Curated1
Sequence conflicti426K → E in AAB81136 (PubMed:9326950).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_027086448 – 541ASKDK…KLGMN → YEDLLCRSLGAGWRAWLGLV LLP in isoform 2. 2 PublicationsAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049507 mRNA Translation: BAC33784.1 Different initiation.
AC123868 Genomic DNA No translation available.
BC046284 mRNA Translation: AAH46284.1
AF003000 mRNA Translation: AAB81136.1 Different initiation.
CCDSiCCDS52666.1 [O35144-2]
RefSeqiNP_001076587.1, NM_001083118.2 [O35144-2]
NP_001273129.1, NM_001286200.1
XP_006530899.1, XM_006530836.3 [O35144-1]
UniGeneiMm.6402

Genome annotation databases

EnsembliENSMUST00000068421; ENSMUSP00000068948; ENSMUSG00000031921 [O35144-1]
ENSMUST00000116425; ENSMUSP00000112126; ENSMUSG00000031921 [O35144-2]
GeneIDi21750
KEGGimmu:21750
UCSCiuc009nhf.2 mouse [O35144-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049507 mRNA Translation: BAC33784.1 Different initiation.
AC123868 Genomic DNA No translation available.
BC046284 mRNA Translation: AAH46284.1
AF003000 mRNA Translation: AAB81136.1 Different initiation.
CCDSiCCDS52666.1 [O35144-2]
RefSeqiNP_001076587.1, NM_001083118.2 [O35144-2]
NP_001273129.1, NM_001286200.1
XP_006530899.1, XM_006530836.3 [O35144-1]
UniGeneiMm.6402

3D structure databases

ProteinModelPortaliO35144
SMRiO35144
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204117, 8 interactors
ComplexPortaliCPX-153 Shelterin complex
CPX-498 Slx4-Terf2 complex
IntActiO35144, 8 interactors
MINTiO35144
STRINGi10090.ENSMUSP00000118759

PTM databases

iPTMnetiO35144
PhosphoSitePlusiO35144

Proteomic databases

EPDiO35144
MaxQBiO35144
PaxDbiO35144
PeptideAtlasiO35144
PRIDEiO35144

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000068421; ENSMUSP00000068948; ENSMUSG00000031921 [O35144-1]
ENSMUST00000116425; ENSMUSP00000112126; ENSMUSG00000031921 [O35144-2]
GeneIDi21750
KEGGimmu:21750
UCSCiuc009nhf.2 mouse [O35144-2]

Organism-specific databases

CTDi7014
MGIiMGI:1195972 Terf2

Phylogenomic databases

eggNOGiENOG410IJXM Eukaryota
ENOG4111KJ3 LUCA
GeneTreeiENSGT00530000063796
HOGENOMiHOG000154547
HOVERGENiHBG108560
InParanoidiO35144
KOiK11111
OrthoDBiEOG091G04CC
PhylomeDBiO35144

Enzyme and pathway databases

ReactomeiR-MMU-171306 Packaging Of Telomere Ends
R-MMU-2559586 DNA Damage/Telomere Stress Induced Senescence

Miscellaneous databases

ChiTaRSiTerf2 mouse
PROiPR:O35144
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031921 Expressed in 280 organ(s), highest expression level in thymus
CleanExiMM_TERF2
ExpressionAtlasiO35144 baseline and differential
GenevisibleiO35144 MM

Family and domain databases

CDDicd11654 TRF2_RBM, 1 hit
Gene3Di1.25.40.210, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017930 Myb_dom
IPR001005 SANT/Myb
IPR013867 Telomere_rpt-bd_fac_dimer_dom
IPR036507 Telomere_rpt-bd_fac_dimer_sf
IPR017357 TERF1/2
IPR030657 TERF2
IPR031902 TERF2_RBM
PANTHERiPTHR21717:SF13 PTHR21717:SF13, 1 hit
PfamiView protein in Pfam
PF00249 Myb_DNA-binding, 1 hit
PF16772 TERF2_RBM, 1 hit
PF08558 TRF, 1 hit
PIRSFiPIRSF038016 Telomere_bd-1_Pin2, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014243 Telomere_repeat-bd_fac_dimer, 1 hit
SMARTiView protein in SMART
SM00717 SANT, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF63600 SSF63600, 1 hit
PROSITEiView protein in PROSITE
PS51294 HTH_MYB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTERF2_MOUSE
AccessioniPrimary (citable) accession number: O35144
Secondary accession number(s): D3YVG5, Q80VE2, Q8BQJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 163 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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