O35144 (TERF2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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:	Trf2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	541 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.7 Ref.8 Ref.9
Subunit structure	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. Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus. Chromosome › telomere. Note: Colocalizes with telomeric DNA in interphase cells and is located at chromosome ends during metaphase. Ref.9
Domain	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.
Post-translational modification	Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites By similarity. Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres By similarity.
Sequence similarities	Contains 1 HTH myb-type DNA-binding domain.
Sequence caution	The sequence AAB81136.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC33784.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Chromosome Nucleus Telomere
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
PTM	Methylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW in utero embryonic development Inferred from mutant phenotype PubMed 15968270. Source: MGI positive regulation of telomere maintenance Inferred from direct assay PubMed 15968270. Source: MGI protection from non-homologous end joining at telomere Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	male germ cell nucleus Inferred from direct assay PubMed 17696610. Source: MGI nuclear chromosome, telomeric region Inferred from direct assay PubMed 15968270PubMed 17696610. Source: MGI nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from electronic annotation. Source: InterPro double-stranded telomeric DNA binding Inferred from mutant phenotype Ref.4. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O35144-1)

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: O35144-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 541	541	Telomeric repeat-binding factor 2		PRO_0000197132
Regions
	Domain	483 – 540	58	HTH myb-type
	DNA binding	511 – 536	26	H-T-H motif By similarity
	Region	87 – 290	204	TRFH dimerization
	Motif	373 – 377	5	Nuclear localization signal Potential
	Compositional bias	58 – 75	18	Arg-rich (basic)
Amino acid modifications
	Modified residue	30	1	Phosphoserine Ref.5
	Modified residue	62	1	Asymmetric dimethylarginine; by PRMT1 By similarity
	Modified residue	63	1	Omega-N-methylarginine By similarity
	Modified residue	233	1	Phosphothreonine; by ATM By similarity
	Modified residue	364	1	Phosphoserine Ref.6
	Modified residue	367	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	448 – 541	94	ASKDK…KLGMN → YEDLLCRSLGAGWRAWLGLV LLP in isoform 2.		VSP_027086
Experimental info
	Mutagenesis	165	1	F → A: Abolishes interaction with DCLRE1B/Apollo, leading to activate the ATM signaling pathway. Ref.7 Ref.9
	Mutagenesis	335 – 336	2	AF → SS: Abolishes interaction with TERF2IP/RAP1 but does not affect protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Ref.9
	Sequence conflict	317	1	Missing in AAB81136. Ref.4
	Sequence conflict	393	1	D → S in AAB81136. Ref.4
	Sequence conflict	426	1	K → E in AAH46284. Ref.3
	Sequence conflict	426	1	K → E in AAB81136. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 2788F7322506182C	FASTA	541	60,263
	10 20 30 40 50 60 MAAGAGTAGP ASGPGVVRDP MASQPRKRPS REGGEGGEGE RRSNTMAGGG GSSDSSGRAA 70 80 90 100 110 120 SRRASRSGGR ARRGRHEPGL GGAAERGAGE ARLEEAVNRW VLKFYFHEAL RAFRSSRYRD 130 140 150 160 170 180 FRQIRDIMQA LLVRPLGKEH TVSRLLRVMQ CLSRIEEGEN LDCSFDMEAE LTPLESAINV 190 200 210 220 230 240 LEMIKTEFTL TDSMVESSRK LVKEAAVIIC IKNKEFEKAS KILKKYMSKD PTTQKLRTDL 250 260 270 280 290 300 LNIIREKNLA HPVIQNFSYE VFQQKMLRFL ESHLDDTEPY LLTMAKKALK SESAASSTMR 310 320 330 340 350 360 EEKHPEPVEK PLREPPSRQP QNPPATIGIR TLKAAFKALS TAQDSEAAFA KLDQKDLVLA 370 380 390 400 410 420 NLASPSSPAH KHKRPRKDEH ESAAPAEGEG GSDRQPRNSP MTISRLLLEE DSQSTEPSPG 430 440 450 460 470 480 LNSSHKAMSA SKPRALNQPH PGEKKPKASK DKWNSPNGLE EKEVWLEEDQ LFEVQAPGED 490 500 510 520 530 540 RSSSLTRKQK WTIEESEWVK DGVRKYGEGN WAAISKSYPF VNRTAVMIKD RWRTMKKLGM N
	Isoform 2 [UniParc]. Checksum: 803C8DD1B0DDFCB0	FASTA	470	51,828
	10 20 30 40 50 60 MAAGAGTAGP ASGPGVVRDP MASQPRKRPS REGGEGGEGE RRSNTMAGGG GSSDSSGRAA 70 80 90 100 110 120 SRRASRSGGR ARRGRHEPGL GGAAERGAGE ARLEEAVNRW VLKFYFHEAL RAFRSSRYRD 130 140 150 160 170 180 FRQIRDIMQA LLVRPLGKEH TVSRLLRVMQ CLSRIEEGEN LDCSFDMEAE LTPLESAINV 190 200 210 220 230 240 LEMIKTEFTL TDSMVESSRK LVKEAAVIIC IKNKEFEKAS KILKKYMSKD PTTQKLRTDL 250 260 270 280 290 300 LNIIREKNLA HPVIQNFSYE VFQQKMLRFL ESHLDDTEPY LLTMAKKALK SESAASSTMR 310 320 330 340 350 360 EEKHPEPVEK PLREPPSRQP QNPPATIGIR TLKAAFKALS TAQDSEAAFA KLDQKDLVLA 370 380 390 400 410 420 NLASPSSPAH KHKRPRKDEH ESAAPAEGEG GSDRQPRNSP MTISRLLLEE DSQSTEPSPG 430 440 450 460 470 LNSSHKAMSA SKPRALNQPH PGEKKPKYED LLCRSLGAGW RAWLGLVLLP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Embryo.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-540 (ISOFORM 1). Tissue: Brain.
[5]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Apollo contributes to G overhang maintenance and protects leading-end telomeres." Wu P., van Overbeek M., Rooney S., de Lange T. Mol. Cell 39:606-617(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DCLRE1B, MUTAGENESIS OF PHE-165.
[8]	"Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression." Teo H., Ghosh S., Luesch H., Ghosh A., Wong E.T., Malik N., Orth A., de Jesus P., Perry A.S., Oliver J.D., Tran N.L., Speiser L.J., Wong M., Saez E., Schultz P., Chanda S.K., Verma I.M., Tergaonkar V. Nat. Cell Biol. 12:758-767(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TERF2IP.
[9]	"Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal." Sfeir A., Kabir S., van Overbeek M., Celli G.B., de Lange T. Science 327:1657-1661(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TERF2IP, MUTAGENESIS OF 335-ALA-PHE-336, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00127599. IPI00466413.
RefSeq	NP_001076587.1. NM_001083118.1.
UniGene	Mm.6402.
3D structure databases
ProteinModelPortal	O35144.
SMR	O35144. Positions 88-294, 326-359, 487-541.
ModBase	Search...
PTM databases
PhosphoSite	O35144.
Proteomic databases
PaxDb	O35144.
PRIDE	O35144.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000068421; ENSMUSP00000068948; ENSMUSG00000031921. ENSMUST00000116425; ENSMUSP00000112126; ENSMUSG00000031921.
GeneID	21750.
KEGG	mmu:21750.
UCSC	uc009nhf.1. mouse.
Organism-specific databases
CTD	7014.
MGI	MGI:1195972. Terf2.
Phylogenomic databases
eggNOG	NOG44337.
GeneTree	ENSGT00530000063796.
HOGENOM	HOG000154547.
HOVERGEN	HBG108560.
InParanoid	O35144.
KO	K11111.
OMA	ITKKQKW.
OrthoDB	EOG4TB4CV.
Enzyme and pathway databases
Reactome	REACT_118161. Cell Cycle. REACT_120463. Meiosis. REACT_75800. Meiotic Synapsis (mouse).
Gene expression databases
ArrayExpress	O35144.
Bgee	O35144.
CleanEx	MM_TERF2.
Genevestigator	O35144.
GermOnline	ENSMUSG00000031921. Mus musculus.
Family and domain databases
Gene3D	1.10.10.60. 1 hit. 1.25.40.210. 1 hit.
InterPro	IPR009057. Homeodomain-like. IPR017930. Myb_dom. IPR001005. SANT/Myb. IPR017357. Telomere_repeat-bd-1/2. IPR013867. Telomere_rpt-bd_fac_dimer_dom. [Graphical view]
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]
SUPFAM	SSF46689. Homeodomain_like. 1 hit. SSF63600. Telo_rept_bnd_D. 1 hit.
PROSITE	PS51294. HTH_MYB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	301043.
SOURCE	Search...

Entry information

Entry name

TERF2_MOUSE

Accession

Primary (citable) accession number: O35144
Secondary accession number(s): D3YVG5, Q80VE2, Q8BQJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program