Peptidyl-tRNA hydrolase 2, mitochondrial (PTRH2)
The protein contains 179 amino acids for an estimated molecular weight of 19194 Da.
The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis.', 'Promotes caspase-independent apoptosis by regulating the function of two transcriptional regulators, AES and TLE1. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| IMNEPD |
The reference OMIM entry for this protein is 608625
Peptidyl-trna hydrolase 2; ptrh2
Bcl2 inhibitor of transcription 1; bit1
DESCRIPTION
The PTRH2 gene encodes a protein that prevents the accumulation of dissociated peptidyl-tRNAs, which could inhibit protein synthesis. PTRH2 is also part of an integrin signaling complex and can function as a phosphoprotein to mediate cell survival and apoptosis (summary by Hu et al., 2014).CLONING
Loss of cell attachment to the extracellular matrix causes apoptosis, a process known as anoikis. BCL2 (151430) is an antiapoptotic protein that can protect cells against anoikis. Jan et al. (2004) searched for proteins involved in cell adhesion-dependent regulation of anoikis by expression cloning for integrin-dependent regulators of BCL2 expression. They identified BIT1, which encodes a predicted 179-amino acid protein with a calculated molecular mass of 27 kD. BIT1 is evolutionarily conserved from bacteria to human. It contains an N-terminal mitochondria localization sequence and a C-terminal UPF0099 domain. Northern blot analysis detected a 1-kb BIT1 transcript expressed prominently in testis, prostate, skeletal muscle, and liver, with lower expression in heart, spleen, placenta, and colon. No significant expression was detected in thymus or peripheral leukocytes. Human embryonic kidney cells showed only trace expression of BIT1. Immunostaining localized endogenous BIT1 to the mitochondria of HeLa cells, and immunoblot analysis revealed a 20-kD doublet in HeLa cell mitochondrial extracts. Hu et al. (2014) found expression of the Ptrh2 gene in various regions of the developing and adult mouse brain, including the neocortex, basal ganglia, hippocampus, and cerebellum. It was expressed in neurons, but not glial cells.GENE FUNCTION
Jan et al. (2004) showed that mitochondrial BIT1 is released into the cytoplasm during apoptosis. Cytoplasmic BIT1 formed a complex with AES (600188) and induced cell death with characteristics of caspase-independent apoptosis. Cell attachment to fibronectin (135600) counteracted the apoptotic effect of BIT1 and AES. Increasing BIT1 expression enhanced anoikis, while suppressing expression reduced it. In in vitro cell-based studies, Griffiths et al. (2011) showed that Bit1 protected cells attached to the extracellular matrix from serum deprivation-mediated apoptosis and from staurosporine-induced mitochondrial apoptosis by promoting phosphorylation of I-kappa-B (see NFKBIA, 164011) and subsequent BCL2 gene transcription downstream of FAK (PTK2; 600758). Knockdown of Bit1 by siRNA promoted apoptosis of cells attached to fibronectin and enhanced staurosporine-induced mitochondrial apoptosis. The findings were consistent with a role for Bit1 as a regulator of integrin-mediated cell survival in cells attached to the extracellular matrix via a FAK/PI3K (171834)/AKT (164730)/NFKB (see 164011) pathway.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PTRH2 gene to chromosome 17 (TMAP RH93739).MOLECULAR GENETICS
In 2 sibs, born of consanguineous Turkish parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD; 616263), Hu et al. (2014) identified a homozygous truncating mutation in the PTRH2 gene (608625.0001). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Patient cells showed decreased cell viability when stressed, which could be rescued by expression of wildtype PTRH2. Patient cells also showed d ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 608625 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).