telomeric repeat-binding factor 2; TTAGGG repeat-binding factor 2; telomeric DNA-binding protein (TERF2 TRBF2 TRF2)

Function: - binds the telomeric double-stranded 5'-TTAGGG-3' repeat & plays a central role in telomere maintenance & protection against end-to-end fusion of chromosomes - in addition to its telomeric DNA-binding role, required to recruit a number of factors & enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 & DCLRE1B/apollo - component of the shelterin complex (telosome) - 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 & repair - required both to recruit DCLRE1B/apollo to telomeres & 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 & TOP2B) needed for telomere replication during fork passage & prevent aberrant telomere topology - recruits TERF2IP/RAP1 to telomeres, thereby participating in repressing homology-directed repair (HDR), which can affect telomere length - phosphorylated upon DNA damage, probably by ATM or ATR - interacts with TERF2IP - interacts with NBN - interacts with SLX4/BTBD12 - interacts with DCLRE1B/apollo & TERF2IP/RAP1 Structure: - homodimer - the TRFH dimerization region mediates the interaction with DCLRE1B/apollo but not TINF2 - contains 1 HTH myb-type DNA-binding domain Compartment: - nucleus, chromosome, telomere - colocalizes with telomeric DNA in interphase cells & is located at chromosome ends during metaphase Alternative splicing: named isoforms=2 Expression: - ubiquitous - highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon & peripheral blood leukocytes

General

peptidyl-prolyl cis/trans isomerase, NIMA-interacting (Pin) telomeric repeat binding factor

Properties

SIZE: entity length = 500 aa MW = 56 kD COMPARTMENT: cell nucleus MOTIF: arginine-rich region {13-30} MOTIF: arginine residue (SEVERAL) TRFH dimerization {42-245} Ser phosphorylation site {S323} nuclear translocation signal {329-333} Ser phosphorylation site {S368} Ser phosphorylation site {S380} HTH myb-type {442-499} MOTIF: DNA-binding motif SITE: 470-495

Database Correlations

OMIM 602027 UniProt Q15554 PFAM correlations Entrez Gene 7014 Kegg hsa:7014 ENZYME

References

UniProt :accession Q15554