ADP-sugar pyrophosphatase (NUDT5)
The protein contains 219 amino acids for an estimated molecular weight of 24328 Da.
Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate (PubMed:27257257). In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10567213, PubMed:10722730, PubMed:19699693, PubMed:21389046, PubMed:17052728). Can also hydrolyze other nucleotide sugars with low activity (PubMed:19699693, PubMed:21389046). In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylated at Thr-45 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity). (updated: Nov. 22, 2017)
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.
- 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 |
|---|---|
| dbSNP:rs34863826 |
Biological Process
ATP generation from poly-ADP-D-ribose
Chromatin remodeling
D-ribose catabolic process
Nucleobase-containing small molecule catabolic process
Nucleobase-containing small molecule metabolic process
Nucleoside phosphate metabolic process
Nucleotide metabolic process
Ribonucleoside diphosphate catabolic process
Ribose phosphate metabolic process
Small molecule metabolic process
Molecular Function
8-oxo-dGDP phosphatase activity
8-oxo-GDP phosphatase activity
ADP-ribose diphosphatase activity
ADP-sugar diphosphatase activity
Identical protein binding
Magnesium ion binding
Nucleoside-diphosphatase activity
Nucleotidyltransferase activity
Protein homodimerization activity
SnoRNA binding
The reference OMIM entry for this protein is 609230
Nucleoside diphosphate-linked moiety x motif 5; nudt5
Nudix motif 5
Ysa1, s. cerevisiae, homolog of; ysa1; ysa1h
DESCRIPTION
Nudix hydrolases, such as NUDT5, eliminate toxic nucleotide derivatives from the cell and regulate the levels of important signaling nucleotides and their metabolites (McLennan, 1999).CLONING
By searching an EST database for sequences similar to S. cerevisiae Ysa1, Gasmi et al. (1999) identified NUDT5, which they designated YSA1H. The deduced 219-amino acid protein has a calculated molecular mass of 24.3 kD. NUDT5 contains a central Nudix motif. Northern blot analysis detected a 1.4-kb transcript in all tissues examined. Minor transcripts of about 5.0 and 1.1 kb were also detected. RNA dot blot analysis revealed NUDT5 expression in all tissues examined. Highest levels were in liver, kidney, pituitary, placenta, and thymus, and lowest levels were in bone marrow, lymph node, and certain areas of brain. Western blot analysis detected NUDT5 at an apparent molecular mass of 33 kD in human nasopharyngeal carcinoma cells, promonocytic cells, and erythrocytes. Bands of about 66 and 64 kD suggested NUDT5 may form dimers. Yang et al. (2000) cloned mouse Nudt5, which encodes a 218-amino acid protein that shares 81% identity with human NUDT5. Northern blot analysis detected Nudt5 expression in all adult mouse tissues analyzed, with highest abundance in liver. RNA dot blot analysis of human tissues detected abundant NUDT5 expression in liver, pituitary, and placenta, as well as in HeLa cervical carcinoma cells.GENE FUNCTION
Gasmi et al. (1999) found that recombinant NUDT5 produced in E. coli was active against ADP-ribose and ADP-mannose. It showed lower activity against ADP-glucose and diadenosine diphosphate. cADP-ribose was not a substrate. Optimal activity was obtained between pH 7.4 and 9.0 in the presence of Mg(2+) or Mn(2+), and fluoride was inhibitory. Yang et al. (2000) confirmed that NUDT5 hydrolyzed ADP-ribose and ADP-mannose in the presence of Mg(2+) or several other divalent cations. They found that the rate of hydrolysis decreased significantly as the nucleoside in ADP-sugar changed from adenosine to guanosine or uridine. Mouse Nudt5 showed slightly different catalytic properties than human NUDT5.GENE STRUCTURE
Yang et al. (2000) determined that the NUDT5 gene contains 9 exons and spans about 18.5 kb. The mouse Nudt5 gene also has 9 exons and spans 13 kb. The introns of the mouse and human genes are in the same positions within their coding sequences.MAPPING
By genomic sequence analysis, Gasmi et al. (1999) mapped the NUDT5 gene to chromosome 10p14-p13. Yang et al. (2000) mapped the mouse Nudt5 gene to a region of chromosome 2 that shows homology of synteny to human chromosome 10. ... More on the omim web site
Feb. 5, 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609230 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed