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Reviewed, UniProtKB/Swiss-Prot Q15554 (TERF2_HUMAN)

Last modified February 9, 2010. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Telomeric repeat-binding factor 2
Alternative name(s):
    TTAGGG repeat-binding factor 2
    Telomeric DNA-binding protein
Gene names
Name: TERF2
Synonyms: TRBF2, TRF2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length500 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Binds the telomeric double-stranded TTAGGG repeat. Protects against end-to-end fusion of chromosomes and plays a role in successful progression through the cell division cycle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG 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. Ref.5 Ref.10

Subunit structure

Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Binds to RAP1. Interacts with NBN. Interacts with BTBD12/SLX4. Ref.6 Ref.19

Subcellular location

Nucleus. 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.

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.20

Sequence similarities

Contains 1 HTH myb-type DNA-binding domain.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentChromosomal protein
Nucleus
Telomere
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processage-dependent telomere shortening

Non-traceable author statement. Source: UniProtKB

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of telomere maintenance via semi-conservative replication

Non-traceable author statement. Source: UniProtKB

protection from non-homologous end joining at telomere

Inferred from mutant phenotype. Source: UniProtKB

protein localization to chromosome, telomeric region

Inferred from mutant phenotype. Source: UniProtKB

regulation of transcription

Inferred from electronic annotation. Source: InterPro

senescence

Non-traceable author statement. Source: UniProtKB

telomere maintenance via telomerase

Inferred by curator. Source: UniProtKB

telomeric loop formation

Inferred from direct assay. Source: UniProtKB

   Cellular componentGolgi apparatus

Inferred from direct assay. Source: HPA

Mre11 complex Ref.6

Inferred from direct assay. Source: UniProtKB

nuclear telomere cap complex

Inferred from direct assay. Source: UniProtKB

nucleoplasm Ref.10

Inferred from Experiment. Source: Reactome

   Molecular functiondouble-stranded telomeric DNA binding Ref.1

Inferred from sequence or structural similarity. Source: UniProtKB

protein C-terminus binding

Inferred from physical interaction. Source: UniProtKB

protein homodimerization activity Ref.1

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15554-1)

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.
Isoform 2 (identifier: Q15554-2)

The sequence of this isoform differs from the canonical sequence as follows:
     239-251: MAKKALKSESAAS → VRLGPSPITMVCP
     252-500: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 500500Telomeric repeat-binding factor 2
PRO_0000197131

Regions

Domain442 – 49958HTH myb-type
DNA binding470 – 49526H-T-H motif
Region46 – 11267Dimerization
Motif329 – 3335Nuclear localization signal Potential
Compositional bias13 – 3018Arg-rich (basic)

Amino acid modifications

Modified residue1691N6-acetyllysine Ref.21
Modified residue3231Phosphoserine Ref.9 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.20
Modified residue3681Phosphoserine Ref.13
Modified residue3801Phosphoserine Ref.13

Natural variations

Alternative sequence239 – 25113MAKKA…ESAAS → VRLGPSPITMVCP in isoform 2.
VSP_003304
Alternative sequence252 – 500249Missing in isoform 2.
VSP_003305
Natural variant4131S → G: dbSNP rs35874485.
VAR_050196

Secondary structure

............................. 500
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 2.
Checksum: 733DCA413BCFBFEE

FASTA50055,551
        10         20         30         40         50         60 
MAGGGGSSDG SGRAAGRRAS RSSGRARRGR HEPGLGGPAE RGAGEARLEE AVNRWVLKFY 

        70         80         90        100        110        120 
FHEALRAFRG SRYGDFRQIR DIMQALLVRP LGKEHTVSRL LRVMQCLSRI EEGENLDCSF 

       130        140        150        160        170        180 
DMEAELTPLE SAINVLEMIK TEFTLTEAVV ESSRKLVKEA AVIICIKNKE FEKASKILKK 

       190        200        210        220        230        240 
HMSKDPTTQK LRNDLLNIIR EKNLAHPVIQ NFSYETFQQK MLRFLESHLD DAEPYLLTMA 

       250        260        270        280        290        300 
KKALKSESAA SSTGKEDKQP APGPVEKPPR EPARQLRNPP TTIGMMTLKA AFKTLSGAQD 

       310        320        330        340        350        360 
SEAAFAKLDQ KDLVLPTQAL PASPALKNKR PRKDENESSA PADGEGGSEL QPKNKRMTIS 

       370        380        390        400        410        420 
RLVLEEDSQS TEPSAGLNSS QEAASAPPSK PTVLNQPLPG EKNPKVPKGK WNSSNGVEEK 

       430        440        450        460        470        480 
ETWVEEDELF QVQAAPDEDS TTNITKKQKW TVEESEWVKA GVQKYGEGNW AAISKNYPFV 

       490        500 
NRTAVMIKDR WRTMKRLGMN 

« Hide

Isoform 2.

Checksum: 13EBD6CF07690DA5
Show »

FASTA25128,256

References

« Hide 'large scale' references
[1]"Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2."
Broccoli D., Smogorzewska A., Chong L., de Lange T.
Nat. Genet. 17:231-235(1997) [PubMed: 9326950] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Mammary carcinoma.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Adrenal cortex.
[3]"Telomeric localization of TRF2, a novel human telobox protein."
Bilaud T., Brun C., Ancelin K., Koering C.E., Larouche T., Gilson E.
Nat. Genet. 17:236-239(1997) [PubMed: 9326951] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-500 (ISOFORM 1).
Tissue: Cervix carcinoma.
[4]"The telobox, a Myb-related telomeric DNA binding motif found in proteins from yeast, plants and human."
Bilaud T., Koering C.E., Binet-Brasselet E., Ancelin K., Pollice A., Gasser S.M., Gilson E.
Nucleic Acids Res. 24:1294-1303(1996) [PubMed: 8614633] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 438-500 (ISOFORM 1).
Tissue: Cervix carcinoma.
[5]"TRF2 protects human telomeres from end-to-end fusions."
van Steensel B., Smogorzewska A., de Lange T.
Cell 92:401-413(1998) [PubMed: 9476899] [Abstract]
Cited for: FUNCTION.
[6]"Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres."
Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.
Nat. Genet. 25:347-352(2000) [PubMed: 10888888] [Abstract]
Cited for: INTERACTION WITH NBN.
[7]"TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres."
Ye J.Z.-S., Donigian J.R., van Overbeek M., Loayza D., Luo Y., Krutchinsky A.N., Chait B.T., de Lange T.
J. Biol. Chem. 279:47264-47271(2004) [PubMed: 15316005] [Abstract]
Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[8]"Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins."
Liu D., O'Connor M.S., Qin J., Songyang Z.
J. Biol. Chem. 279:51338-51342(2004) [PubMed: 15383534] [Abstract]
Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[9]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"Shelterin: the protein complex that shapes and safeguards human telomeres."
de Lange T.
Genes Dev. 19:2100-2110(2005) [PubMed: 16166375] [Abstract]
Cited for: FUNCTION OF THE SHELTERIN COMPLEX.
[11]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
Tissue: Epithelium.
[12]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368 AND SER-380, MASS SPECTROMETRY.
[14]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
[15]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
[17]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
[19]"Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair."
Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P., Elledge S.J., Harper J.W.
Cell 138:63-77(2009) [PubMed: 19596235] [Abstract]
Cited for: INTERACTION WITH BTBD12.
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY.
Tissue: T-cell.
[21]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-169, MASS SPECTROMETRY.
[22]"Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2."
Fairall L., Chapman L., Moss H., de Lange T., Rhodes D.
Mol. Cell 8:351-361(2001) [PubMed: 11545737] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF002999 mRNA. Translation: AAB81135.1.
BC024890 mRNA. Translation: AAH24890.1.
U95970 mRNA. Translation: AAD00821.1.
X93512 mRNA. Translation: CAA63769.1.
IPIIPI00024214.
IPI00216552.
PIRS67923.
RefSeqNP_005643.1.
UniGeneHs.63335

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H6PX-ray2.20A/B43-245[»]
1VF9NMR-A438-500[»]
1VFCNMR-A438-500[»]
1W0UX-ray1.80A/B446-500[»]
1XG1NMR-A438-500[»]
3BU8X-ray2.15A/B42-276[»]
3BUAX-ray2.50A/B/C/D42-245[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ15554. 9 interactions.
STRINGQ15554.

PTM databases

PhosphoSiteQ15554.

Proteomic databases

PRIDEQ15554.

Genome annotation databases

EnsemblENST00000254942; ENSP00000254942; ENSG00000132604; Homo sapiens. [Genome view]
GeneID7014.
KEGGhsa:7014.
UCSCuc002exd.1. human.
uc002exe.2. human.

Organism-specific databases

CTD7014.
GeneCardsGC16M067947.
H-InvDBHIX0013184.
HGNCHGNC:11729. TERF2.
HPACAB010451.
HPA001907.
HPA002735.
MIM602027. gene.
PharmGKBPA36446.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16406.
HOGENOMHBG283423.
HOVERGENQ15554.
InParanoidQ15554.
OMAGDFRQIR.
OrthoDBEOG94N1C2.
PhylomeDBQ15554.

Enzyme and pathway databases

Pathway_Interaction_DBtelomerasepathway. Regulation of Telomerase.
ReactomeREACT_7970. Telomere Maintenance.

Gene expression databases

ArrayExpressQ15554.
BgeeQ15554.
CleanExHS_TERF2.
GenevestigatorQ15554.
GermOnlineENSG00000132604. Homo sapiens.

Family and domain databases

InterProIPR009057. Homeodomain-like.
IPR012287. Homeodomain-rel.
IPR017930. HTH_Myb-type_DNA-bd.
IPR014778. Myb_DNA-bd.
IPR001005. SANT_DNA-bd.
IPR017357. Telomere_repeat-bd-1_Pin2.
IPR013867. Telomere_rpt-bd_fac_dimer_dom.
[Graphical view]
Gene3DG3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
G3DSA:1.25.40.210. Telomere_repeat-bd_fac_dimer. 1 hit.
PfamPF00249. Myb_DNA-binding. 1 hit.
PF08558. TRF. 1 hit.
[Graphical view]
PIRSFPIRSF038016. Telomere_bd-1_Pin2. 1 hit.
ProDomPD014243. Telomere_repeat-bd_fac_dimer. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00717. SANT. 1 hit.
[Graphical view]
PROSITEPS51294. HTH_MYB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio27401.
SOURCESearch...

Entry information

Entry nameTERF2_HUMAN
AccessionPrimary (citable) accession number: Q15554
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: November 1, 1998
Last modified: February 9, 2010
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents