Reviewed, UniProtKB/Swiss-Prot Q15554 (TERF2_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cell cycle
Cellular component	Chromosomal protein Nucleus Telomere
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	age-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 component	Golgi 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 function	double-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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BLM	P54132	5	EBI-706637,EBI-621372
BTBD12	Q8IY92	1	EBI-706637,EBI-2370740
POT1	Q9NUX5	1	EBI-706637,EBI-752420
TERF2IP	Q9NYB0	1	EBI-706637,EBI-750109
TINF2	Q9BSI4-3	1	EBI-706637,EBI-717418
WRN	Q14191	4	EBI-706637,EBI-368417

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 500

500

Telomeric repeat-binding factor 2

PRO_0000197131

Regions

Domain

442 – 499

58

HTH myb-type

DNA binding

470 – 495

26

H-T-H motif

Region

46 – 112

67

Dimerization

Motif

329 – 333

5

Nuclear localization signal Potential

Compositional bias

13 – 30

18

Arg-rich (basic)

Amino acid modifications

Modified residue

169

1

N6-acetyllysine Ref.21

Modified residue

323

1

Phosphoserine Ref.9 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.20

Modified residue

368

1

Phosphoserine Ref.13

Modified residue

380

1

Phosphoserine Ref.13

Natural variations

Alternative sequence

239 – 251

13

MAKKA…ESAAS → VRLGPSPITMVCP in isoform 2.

VSP_003304

Alternative sequence

252 – 500

249

Missing in isoform 2.

VSP_003305

Natural variant

413

1

S → G: dbSNP rs35874485.

VAR_050196

Secondary structure

1

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500

Helix Strand Turn

Details...

Helix

44 – 69

26

Helix

73 – 86

14

Helix

98 – 111

14

Turn

112 – 114

3

Helix

128 – 142

15

Helix

147 – 167

21

Helix

171 – 181

11

Helix

193 – 201

9

Turn

202 – 204

3

Helix

214 – 227

14

Helix

235 – 244

10

Turn

440 – 443

4

Helix

452 – 465

14

Helix

470 – 476

7

Helix

484 – 496

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 733DCA413BCFBFEE	FASTA	500	55,551
	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
	Isoform 2. Checksum: 13EBD6CF07690DA5	FASTA	251	28,256
	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 DAEPYLLTVR 250 LGPSPITMVC P

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00024214.
IPI00216552.

PIR

S67923.

RefSeq

NP_005643.1.

UniGene

Hs.63335

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H6P	X-ray	2.20	A/B	43-245	[»]
1VF9	NMR	-	A	438-500	[»]
1VFC	NMR	-	A	438-500	[»]
1W0U	X-ray	1.80	A/B	446-500	[»]
1XG1	NMR	-	A	438-500	[»]
3BU8	X-ray	2.15	A/B	42-276	[»]
3BUA	X-ray	2.50	A/B/C/D	42-245	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15554. 9 interactions.

STRING

Q15554.

PTM databases

PhosphoSite

Q15554.

Proteomic databases

PRIDE

Q15554.

Genome annotation databases

Ensembl

ENST00000254942; ENSP00000254942; ENSG00000132604; Homo sapiens. [Genome view]

GeneID

7014.

KEGG

hsa:7014.

UCSC

uc002exd.1. human.
uc002exe.2. human.

Organism-specific databases

CTD

7014.

GeneCards

GC16M067947.

H-InvDB

HIX0013184.

HGNC

HGNC:11729. TERF2.

HPA

CAB010451.
HPA001907.
HPA002735.

MIM

602027. gene.

PharmGKB

PA36446.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16406.

HOGENOM

HBG283423.

HOVERGEN

Q15554.

InParanoid

Q15554.

OMA

GDFRQIR.

OrthoDB

EOG94N1C2.

PhylomeDB

Q15554.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Reactome

REACT_7970. Telomere Maintenance.

Gene expression databases

ArrayExpress

Q15554.

Bgee

Q15554.

CleanEx

HS_TERF2.

Genevestigator

Q15554.

GermOnline

ENSG00000132604. Homo sapiens.

Family and domain databases

InterPro

IPR009057. 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]

Gene3D

G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
G3DSA:1.25.40.210. Telomere_repeat-bd_fac_dimer. 1 hit.

Pfam

PF00249. Myb_DNA-binding. 1 hit.
PF08558. TRF. 1 hit.
[Graphical view]

PIRSF

PIRSF038016. Telomere_bd-1_Pin2. 1 hit.

ProDom

PD014243. Telomere_repeat-bd_fac_dimer. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00717. SANT. 1 hit.
[Graphical view]

PROSITE

PS51294. HTH_MYB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27401.

SOURCE

Search...

Entry information

Entry name

TERF2_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.