Telomeric repeat-binding factor 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''TERF1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Gene

The human TERF1 gene is located in the chromosome 8 at 73,921,097-73,960,357 bp. Two transcripts of this gene are alternatively spliced products. The TERF1 gene is also known as TRF, PIN2 (Proteinase Inhibitor 2), TRF1, t-TRF1 and h-TRF1-AS.

Protein

The protein structure contains a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

Myb motif, a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer ** TH-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * ...

ization domain (TERF homology) near its

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

and an acidic N-terminus.

Subcellular distribution

The cellular distribution of this DNA binding protein features the

nucleoplasm The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleoplasm r ...

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

s, a telomeric region, a nuclear

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...

cap complex, the cytoplasm, the

spindle Spindle may refer to: Textiles and manufacturing * Spindle (textiles), a straight spike to spin fibers into yarn * Spindle (tool), a rotating axis of a machine tool Biology * Common spindle and other species of shrubs and trees in genus ''Euonym ...

, the

nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...

and a

nucleolus The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

and a nuclear chromosome.

Function

TERF 1 gene encodes a telomere specific protein which is a component of the telomere's

shelterin Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double ...

nucleoprotein complex. This protein is present at telomeres throughout the cell cycle and functions as an inhibitor of

telomerase Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...

, acting in cis to limit the elongation of individual chromosome ends. It is known to protect telomeres in mammals from DNA mechanisms that are used for repair purposes and at the same time regulate the activity carried out by telomerase. The telomeric repeat binding factor 1 protein is present at telomeres, where the cells aging aspect is monitored, throughout the typical cell cycle process. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1) is a protein that binds at telomere ends. The protein has the ultimate use of functioning as an inhibitor of telomerase, a protein enzyme that assists in the elongation of chromosomes by the addition of sequences of TTAGGG to the end of the chromosomes. The protein acts as cis-regulatory elements in the process of limiting the ends of individual chromosomes from elongating as facilitated by telomerase and the TTAGGG sequences. The structure of the protein consists of a dimerization domain close to its amino terminus, a

carboxyl In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g. ...

terminal tail, which is the free carboxyl group that terminates the end of a protein chain and an acidic amino terminus, which is the free amine group that terminates the start of a protein.

Biological processes

The protein is also actively involved in biological processes such as those relating to drug absorption as well as the negative regulation of the maintenance of telomere through the process of semi-conservative replication, similar to that of cis. In addition, according to Kaplan and Christopher, the protein is also involved in the biological processes of positive regulation of the polymerization of the microtubule and negative control of the process of DNA replication. This protein is also useful in the biological process of mitosis and the positive regulation of mitosis. It positively regulates the mitotic cell cycle. The protein encoded by the TERF 1 gene is also involved in the biological process of cell division and the negative regulation of the maintenance of telomere facilitated by the enzyme telomerase. Other than functioning as an inhibitor of the enzyme telomerase in the process of elongation of the ends of chromosomes, the protein has other functions. These functions include the binding of the protein, facilitation in the activity of protein homodimerization, the binding of DNA and facilitation in the activity of protein heterodimerization as well as the binding of the microtubule. Additionally, the protein has a molecular function of binding telomeric DNA and the double-stranded telomeric DNA. The telomeric repeat-binding factor 1 protein is also used in the binding of chromatin and the whole activity of bending of the DNA.

Clinical significance

TERF1 protein levels correlates with telomere length in colorectal cancer. Telomeres protect the chromosome from degradation by nucleases and end-to-end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1) is a protein that binds at telomere ends. To measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa, from normal and tumoral samples of patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration, and telomerase activity were analysed. As result high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels. In conclusion a relationship exists between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor.

Interactions

The TERF1 encoded protein has been shown to have interactions with the following;

SALL1 Sal-like 1 (Drosophila), also known as SALL1, is a protein which in humans is encoded by the ''SALL1'' gene. As the full name suggests, it is one of the human versions of the ''spalt'' (''sal'') gene known in ''Drosophila''. Function The prot ...

(Sal-like1- Drosophila, a protein.),

ABL ABL may refer to: Aviation * Airborne Laser, a weapons system designed for use by the United States military * Air Busan of South Korea (ICAO airline code) * IATA airport code for Ambler Airport in State of Alaska, USA Companies, groups, organiz ...

(Abelson murine leukemia viral oncogene homolog, a protein),

MAPRE2 Microtubule-associated protein RP/EB family member 2 is a protein that in humans is encoded by the ''MAPRE2'' gene. Function The protein encoded by this gene shares significant homology to the adenomatous polyposis coli (APC) protein-binding ...

(Microtubule-associated protein RP/EB, a protein), ATM (Ataxia telangiectasia mutated, a protein kinase),

PINX1 ''PIN2/TERF1''-interacting telomerase inhibitor 1, also known as ''PINX1'', is a human gene. ''PINX1'' is also known as ''PIN2'' interacting protein 1. ''PINX1'' is a telomerase inhibitor and a possible tumor suppressor. Interactions PINX1 has be ...

(TERF1-interacting telomerase inhibitor 1),

TINF2 TERF1-interacting nuclear factor 2 is a protein that in humans is encoded by the ''TINF2'' gene. TINF2 is a component of the shelterin protein complex found at the end of telomeres. Interactions TINF2 has been shown to interact with ACD, POT ...

(TERF1-interacting telomerase nuclear factor),

TNKS2 Tankyrase-2 is an enzyme that in humans is encoded by the ''TNKS2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed ...

(Tankyrase, an enzyme) and

NME1 Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the ''NME1'' gene. It is thought to be a metastasis suppressor. Function This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metast ...

(nucleoside diphosphate kinase).In conclusion, as mentioned above, the telomeric repeat-binding factor 1 protein has most of its functions related to the binding of components and regulation of processes. TERF1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: *

Abl gene Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ''ABL1'' gene (previous symbol ''ABL'') located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammali ...

, *

Ataxia telangiectasia mutated ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA repair#Double-strand breaks, DNA double-strand breaks (Canonical pathway, canonical pathway), o ...

, *

MAPRE1 Microtubule-associated protein RP/EB family member 1 is a protein that in humans is encoded by the ''MAPRE1'' gene. Function The protein encoded by this gene was first identified by its binding to the APC (Adenomatous polyposis coli) protein ...

, *

, and *

TNKS Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the ''TNKS'' gene. It inhibits the binding of TERF1 to telomeric DNA. Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 a ...