TIP41-like protein (TIPRL)
The protein contains 272 amino acids for an estimated molecular weight of 31444 Da.
May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AX phosphorylated on Ser-140 (gamma-H2AX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair. (updated: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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Biological Process
DNA damage checkpoint signaling
Negative regulation of phosphoprotein phosphatase activity
Negative regulation of protein phosphatase type 2A activity
Regulation of phosphoprotein phosphatase activity
Signal transduction
TOR signaling
Molecular Function
The reference OMIM entry for this protein is 611807
Tip41-like protein; tiprl
Tip41, s. cerevisiae, homolog of; tip41
Protein phosphatase 2a-interacting protein; tip
DESCRIPTION
TIPRL is an inhibitory regulator of protein phosphatase-2A (PP2A) (see PPP2CA; 176915), PP4 (see PPP4C; 602035), and PP6 (see PPP6C; 612725) (McConnell et al., 2007).CLONING
By database analysis, Jacinto et al. (2001) identified human TIPRL as a homolog of yeast Tip41. TIPRL shares 35% amino acid identity with the yeast protein. McConnell et al. (2007) cloned human TIPRL, which they called TIP, from a T-cell lymphoma cDNA library. The predicted protein contains 272 amino acids. They also cloned a TIP splice variant that encodes a C-terminally truncated protein (TIP isoform-2) that shares the first 172 amino acids with TIP, but ends with 6 unique amino acids. Immunoblot analysis showed ubiquitous expression of a 33-kD TIP protein.GENE FUNCTION
Using immunoprecipitation analysis, McConnell et al. (2007) found that, unlike yeast Tip41, human TIP did not interact with alpha-4 (IGBP1; 300139), the human homolog of yeast Tap42, in the presence of rapamycin. Instead, TIP interacted with the catalytic subunits of PP2A, PP4, and PP6 in a rapamycin-independent manner. TIP isoform-2 did not interact with PP2A, suggesting that the C terminus of TIP is important for PP2A binding. Incubation of PP2A with TIP, but not TIP isoform-2, resulted in dose-dependent inhibition of PP2A phosphatase activity. Cells in which TIP was depleted by small interfering RNA exhibited decreased phosphorylation of a 32-kD substrate of ATM (607585)/ATR (601215) kinases. McConnell et al. (2007) concluded that TIP is an inhibitory regulator of PP2A and that the TIP/PP2A complex has a role within the ATM/ATR signaling pathway controlling DNA replication and repair.GENE STRUCTURE
McConnell et al. (2007) determined that the TIPRL gene contains 7 exons. Exons 1 through 4, 6, and 7 encode TIP, and exons 1 through 5 encode TIP isoform-2.MAPPING
By genomic sequence analysis, McConnell et al. (2007) mapped the TIPRL gene to chromosome 1q23.2. ... More on the omim web site
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 611807 was added.