Hypoxia up-regulated protein 1 (HYOU1)
The protein contains 999 amino acids for an estimated molecular weight of 111335 Da.
Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. May play a role as a molecular chaperone and participate in protein folding. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
- 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.
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| Variant | Description |
|---|---|
| IMD59; unknown pathological significance | |
| IMD59; unknown pathological significance |
Biological Process
Cellular response to hypoxia
Endoplasmic reticulum to Golgi vesicle-mediated transport
IRE1-mediated unfolded protein response
Negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway
Negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway
Receptor-mediated endocytosis
Response to endoplasmic reticulum stress
Response to ischemia
The reference OMIM entry for this protein is 601746
Hypoxia up-regulated 1; hyou1
Oxygen-regulated protein, 150-kd; orp150
CLONING
Astrocytes retain cell viability, even in extreme ischemia, and proliferate in damaged brain (Petito et al., 1990; Janeczko, 1991). Rat astrocytes exposed to hypoxia followed by reoxygenation were reported to release increased amounts of interleukin-6 (147620) that could promote neuronal survival in ischemic brain (Maeda et al., 1994). Kuwabara et al. (1996) observed a 150-kD protein, called oxygen-regulated protein (ORP150) by them, in the endoplasmic reticulum (ER) of cultured astrocytes that was induced specifically by hypoxia and not by other stimuli. Ikeda et al. (1997) reported the cloning of human and rat ORP150 cDNAs from hypoxia-treated human astrocytoma U373 cells and rat astrocytes, respectively. The full-length 4,503-bp human cDNA contains a 2,997-bp open reading frame predicted to encode a polypeptide of 999 amino acids with a calculated molecular mass of 111,330 Da. The deduced amino acid sequences of human and rat ORP150 exhibit high similarity (over 90% identity) to each other. The first 32 residues represent the signal peptide necessary for secretion. The C-terminal KNDEL sequence resembles KDEL, a motif found in ER-resident proteins, suggesting that ORP150 resides in the ER. The N-terminal half of ORP150 has a modest similarity to the ATPase domain of numerous HSP70 family sequences (see 140550). Northern blot analysis revealed a marked similarity of expression between ORP150 and GRP78 (138120) in U373 cells during hypoxia stress. (The GRP78 protein is produced in cultured rat astrocytes exposed to hypoxia or hypoxia/reoxygenation.) They also found that ORP150 mRNA was highly expressed in the liver and pancreas, whereas little expression was observed in the kidney and brain, similarly to the expression pattern of GRP78. Ikeda et al. (1997) proposed that ORP150 plays an important role in protein folding and secretion in the ER, perhaps as a molecular chaperone in concert with other GRPs, to cope with environmental stress.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HYOU1 gene to chromosome 11 (TMAP stSG31085).GENE FUNCTION
Tamatani et al. (2001) found that although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) (113505) under hypoxia signaling. Tamatani et al. (2001) concluded that ORP150 is an integral participant in ischemic cytoprotective pathways. Ozawa et al. (2001) demonstrated coexpression, colocalization, and coimmunoprecipitation of ORP150 and vascular endothelial growth factor (VEGF; 192240) in the ER of macrophages within the neovasculature of human wound granulation tissue. In vitro, inhibition of ORP150 resulted in retention of VEGF within the ER, whereas overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants, indicating that ORP150 may participate in VEGF transport to the cytoplasm. In wounds of diabetic mice, overexpression of ORP150 resulted in accelerated repair and closure; suppression of ORP150 delayed repair. Ozawa et al. (2001) concluded that ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 601746 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).