UniProt functional annotation for Q15554



	UniProt functional annotation for Q15554

UniProt code: Q15554.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:20655466, ECO:0000269|PubMed:9476899}.

Subunit: 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 and TERF2IP/RAP1; the interaction is direct. {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:15316005, ECO:0000269|PubMed:15383534, ECO:0000269|PubMed:15608617, ECO:0000269|PubMed:16606622, ECO:0000269|PubMed:16730175, ECO:0000269|PubMed:16730176, ECO:0000269|PubMed:18202258, ECO:0000269|PubMed:18468965, ECO:0000269|PubMed:18593705, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:20655466}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00625, ECO:0000269|PubMed:20655466}. Chromosome, telomere {ECO:0000269|PubMed:20655466}. 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.

Domain: The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2. {ECO:0000269|PubMed:18202258}.

Domain: The HTH domain is an independent structural unit and mediates binding to telomeric DNA. {ECO:0000269|PubMed:18202258}.

Ptm: Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites. {ECO:0000269|PubMed:16223874}.

Ptm: Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres. {ECO:0000269|PubMed:19596784}.

Sequence caution: Sequence=AAB81135.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB81135.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={ECO:0000305}; Sequence=AAH24890.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:16166375, ECO:0000269\|PubMed:20655466, ECO:0000269\|PubMed:9476899}.


Subunit:		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 and TERF2IP/RAP1; the interaction is direct. {ECO:0000269\|PubMed:10888888, ECO:0000269\|PubMed:15316005, ECO:0000269\|PubMed:15383534, ECO:0000269\|PubMed:15608617, ECO:0000269\|PubMed:16606622, ECO:0000269\|PubMed:16730175, ECO:0000269\|PubMed:16730176, ECO:0000269\|PubMed:18202258, ECO:0000269\|PubMed:18468965, ECO:0000269\|PubMed:18593705, ECO:0000269\|PubMed:19596235, ECO:0000269\|PubMed:20655466}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00625, ECO:0000269\|PubMed:20655466}. Chromosome, telomere {ECO:0000269\|PubMed:20655466}. 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.
Domain:		The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2. {ECO:0000269\|PubMed:18202258}.
Domain:		The HTH domain is an independent structural unit and mediates binding to telomeric DNA. {ECO:0000269\|PubMed:18202258}.
Ptm:		Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites. {ECO:0000269\|PubMed:16223874}.
Ptm:		Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres. {ECO:0000269\|PubMed:19596784}.
Sequence caution:		Sequence=AAB81135.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB81135.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={ECO:0000305}; Sequence=AAH24890.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};