Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP)

The protein contains 399 amino acids for an estimated molecular weight of 44260 Da.

 

Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 29%
Model score: 35
MODL_I-TASSER-3.0
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs4888444

The reference OMIM entry for this protein is 605061

Terf2-interacting protein; terf2ip
Trf2-interacting telomeric protein
Rap1, yeast, homolog of; rap1

CLONING

By performing a yeast 2-hybrid screen on a HeLa cell cDNA library using telomeric repeat-binding factor-2, or TRF2 (TERF2; 602027), as bait, followed by screening a breast cancer cDNA library, Li et al. (2000) isolated a full-length cDNA encoding RAP1, an ortholog of the yeast telomeric protein Rap1. The RAP1 cDNA is identical to the KAIA804 cDNA (GenBank GENBANK AK000669) reported by the NEDO Japanese sequencing project. The predicted 47-kD RAP1 protein contains 399 amino acids. A motif search revealed that RAP1 has an N-terminal BRCT domain and a central Myb-type helix-turn-helix motif. RAP1 also has an acidic C terminus (amino acids 214 to 382; pI around 3.8) featuring a predicted 33-amino acid coiled-coil region and a bipartite nuclear localization signal. Sequence alignments showed an additional region of sequence similarity in the C termini of yeast and human RAP1 that coincides with the main protein-protein interaction domain of S. cerevisiae Rap1. Thus, human RAP1 has 3 conserved sequence motifs in common with yeast Rap1. Northern blot analysis detected ubiquitous expression of a 2.5-kb RAP1 transcript. The authors found that RAP1 is localized to telomeres and affects telomere length. However, while yeast Rap1 binds telomeric DNA directly, human RAP1 is recruited to telomeres by TRF2. Extending the comparison of telomeric proteins to fission yeast, Li et al. (2000) identified the S. pombe Taz1 protein as a TRF ortholog, indicating that TRFs are conserved at eukaryotic telomeres. The data suggested that ancestral telomeres, like those of vertebrates, contained a TRF-like protein as well as RAP1. The authors proposed that budding yeast preserved Rap1 at telomeres but lost the TRF component, possibly concomitant with a change in the telomeric repeat sequence.

GENE FUNCTION

Lieb et al. (2001) determined the distribution of RAP1 in vivo on the entire yeast genome, at a resolution of 2 kb. RAP1 is central to the cellular economy during rapid growth, targeting 294 loci, about 5% of yeast genes, and participating in the activation of 37% of all RNA polymerase II (see 180660) initiation events in exponentially growing cells. Although the DNA sequence recognized by RAP1 is found in both coding and intergenic sequences, the binding of RAP1 to the genome was highly specific to intergenic regions with the potential to act as promoters. Lieb et al. (2001) concluded that this global phenomenon, which may be a general characteristic of sequence-specific transcriptional factors, indicates the existence of a genomewide molecular mechanism for marking promoter regions. Sfeir et al. (2010) removed Rap1 from mouse telomeres either through gene deletion or by replacing Trf2 (602027) with a mutant that does not bind Rap1. Rap1 was dispensable for the essential functions of Trf2--repression of ATM kinase signaling and nonhomologous end-joining--and mice lacking telomeric Rap1 were viable and fertile. However, Rap1 was critical for the repression of homology-directed repair, which can alter telomere length. The data of Sfeir et al. (2010) revealed that homology-directed repair at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within the shelterin complex.

BIOCHEMICAL FEATURES

- Cryoelectron Microscopy Papai et al. (2010) used cryoelectron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID (313650), TFIIA (see 600519) ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605061 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed