UniProt functional annotation for P54274



	UniProt functional annotation for P54274

UniProt code: P54274.

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 negatively regulates telomere length. Involved in the regulation of the mitotic spindle. 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. {ECO:0000269|PubMed:16166375}.

Subunit: Homodimer; can contain both isoforms. Found in a complex with POT1; TINF2 and TNKS1. Interacts with ATM, TINF2, TNKS1, TNKS2, PINX1, NEK2 and MAPRE1. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with RLIM (via N-terminus). Interacts with FBXO4. Interaction with TINF2 protects against interaction with FBXO4 and subsequent polyubiquitination and proteasomal degradation. Interacts with GNL3L; this interaction promotes homodimerization. Interacts with TIN2. Interacts with RTEL1. Interactions with GNL3L and TIN2 are mutually exclusive. Interacts with CCDC79/TERB1 (By similarity). {ECO:0000250}.

Subcellular location: Nucleus. Cytoplasm, cytoskeleton, spindle. Chromosome, telomere. Note=Colocalizes with telomeric DNA in interphase and prophase cells. Telomeric localization decreases in metaphase, anaphase and telophase. Associates with the mitotic spindle.

Tissue specificity: Highly expressed and ubiquitous. Isoform Pin2 predominates.

Induction: Expression is tightly regulated during the cell cycle; levels are low in G1 and S phase and increase during G2 phase and mitosis.

Domain: The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules. {ECO:0000269|PubMed:18202258}.

Domain: The TRFH dimerization region mediates the interaction with 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 preferentially on Ser-219 in an ATM-dependent manner in response to ionizing DNA damage. {ECO:0000269|PubMed:11375976}.

Ptm: ADP-ribosylation by TNKS1 or TNKS2 diminishes its ability to bind to telomeric DNA.

Ptm: Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin- protein ligase complex, leading to its degradation by the proteasome. {ECO:0000269|PubMed:19164295, ECO:0000269|PubMed:20159592}.

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 negatively regulates telomere length. Involved in the regulation of the mitotic spindle. 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. {ECO:0000269\|PubMed:16166375}.


Subunit:		Homodimer; can contain both isoforms. Found in a complex with POT1; TINF2 and TNKS1. Interacts with ATM, TINF2, TNKS1, TNKS2, PINX1, NEK2 and MAPRE1. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with RLIM (via N-terminus). Interacts with FBXO4. Interaction with TINF2 protects against interaction with FBXO4 and subsequent polyubiquitination and proteasomal degradation. Interacts with GNL3L; this interaction promotes homodimerization. Interacts with TIN2. Interacts with RTEL1. Interactions with GNL3L and TIN2 are mutually exclusive. Interacts with CCDC79/TERB1 (By similarity). {ECO:0000250}.
Subcellular location:		Nucleus. Cytoplasm, cytoskeleton, spindle. Chromosome, telomere. Note=Colocalizes with telomeric DNA in interphase and prophase cells. Telomeric localization decreases in metaphase, anaphase and telophase. Associates with the mitotic spindle.
Tissue specificity:		Highly expressed and ubiquitous. Isoform Pin2 predominates.
Induction:		Expression is tightly regulated during the cell cycle; levels are low in G1 and S phase and increase during G2 phase and mitosis.
Domain:		The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules. {ECO:0000269\|PubMed:18202258}.
Domain:		The TRFH dimerization region mediates the interaction with 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 preferentially on Ser-219 in an ATM-dependent manner in response to ionizing DNA damage. {ECO:0000269\|PubMed:11375976}.
Ptm:		ADP-ribosylation by TNKS1 or TNKS2 diminishes its ability to bind to telomeric DNA.
Ptm:		Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin- protein ligase complex, leading to its degradation by the proteasome. {ECO:0000269\|PubMed:19164295, ECO:0000269\|PubMed:20159592}.