CPLM-012582

Genbank Nucleotide ID

Telomeric repeat-binding factor 2

Protein Synonyms/Alias

TTAGGG repeat-binding factor 2; Telomeric DNA-binding protein

Homo sapiens (Human)

Position	Peptide	Type	References
93	LLVRPLGKEHTVSRL	ubiquitination	[1]
169	VIICIKNKEFEKASK	acetylation	[2, 3]
173	IKNKEFEKASKILKK	acetylation	[2, 3]
241	PYLLTMAKKALKSES	ubiquitination	[4]
242	YLLTMAKKALKSESA	ubiquitination	[4]
293	MTLKAAFKTLSGAQD	ubiquitination	[5, 6, 7]
390	AASAPPSKPTVLNQP	ubiquitination	[8]
402	NQPLPGEKNPKVPKG	ubiquitination	[8, 9]
446	DSTTNITKKQKWTVE	acetylation	[10]
447	STTNITKKQKWTVEE	acetylation	[10]
449	TNITKKQKWTVEESE	acetylation	[10]
488	NRTAVMIKDRWRTMK	acetylation	[10]
495	KDRWRTMKRLGMN**	acetylation	[10]

[1] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[3] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[8] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[10] A mass spectrometric approach to the study of DNA-binding proteins: interaction of human TRF2 with telomeric DNA.
Sperry JB, Shi X, Rempel DL, Nishimura Y, Akashi S, Gross ML.
Biochemistry. 2008 Feb 12;47(6):1797-807. [PMID: 18197706]

Functional Description

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.

DOMAIN 442 499 HTH myb-type.
DNA_BIND 470 495 H-T-H motif.
REGION 42 245 TRFH dimerization.
MOTIF 329 333 Nuclear localization signal (Potential).
MOD_RES 17 17 Asymmetric dimethylarginine; by PRMT1.
MOD_RES 18 18 Omega-N-methylarginine.
MOD_RES 188 188 Phosphothreonine; by ATM.
MOD_RES 323 323 Phosphoserine.

3D-structure; Alternative splicing; Cell cycle; Chromosome; Complete proteome; DNA-binding; Methylation; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Telomere.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005794; C:Golgi apparatus; IDA:HPA.
GO:0001673; C:male germ cell nucleus; IEA:Compara.
GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0003682; F:chromatin binding; IEA:InterPro.
GO:0003691; F:double-stranded telomeric DNA binding; ISS:BHF-UCL.
GO:0001309; P:age-dependent telomere shortening; NAS:BHF-UCL.
GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO:0090398; P:cellular senescence; NAS:BHF-UCL.
GO:0001701; P:in utero embryonic development; IEA:Compara.
GO:0032214; P:negative regulation of telomere maintenance via semi-conservative replication; NAS:BHF-UCL.
GO:0032206; P:positive regulation of telomere maintenance; IEA:Compara.
GO:0031848; P:protection from non-homologous end joining at telomere; IMP:BHF-UCL.
GO:0070198; P:protein localization to chromosome, telomeric region; IMP:BHF-UCL.
GO:0007004; P:telomere maintenance via telomerase; IC:BHF-UCL.
GO:0031627; P:telomeric loop formation; IDA:BHF-UCL.

IPR009057; Homeodomain-like.
IPR017930; Myb_dom.
IPR001005; SANT/Myb.
IPR017357; Telomere_repeat-bd-1/2.
IPR013867; Telomere_rpt-bd_fac_dimer_dom.

PF00249; Myb_DNA-binding
PF08558; TRF