Adenosine kinase (ADK)
The protein contains 362 amino acids for an estimated molecular weight of 40545 Da.
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides. (updated: April 1, 2015)
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.
- 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.
This protein is annotated as membranous in Gene Ontology.
Biological Process
Adenosine metabolic process
Adenosine salvage
AMP salvage
Carbohydrate phosphorylation
Circadian regulation of gene expression
DATP biosynthetic process
Nucleobase-containing small molecule metabolic process
Positive regulation of cardiac muscle hypertrophy
Positive regulation of T cell proliferation
Purine nucleobase metabolic process
Purine ribonucleoside salvage
Purine-containing compound salvage
Ribonucleoside monophosphate biosynthetic process
Small molecule metabolic process
Type B pancreatic cell proliferation
The reference OMIM entry for this protein is 102750
Adenosine kinase; adk
DESCRIPTION
The ADK gene encodes adenosine kinase (ATP:adenosine 5-prime-phosphotransferase; EC 2.7.1.20), an abundant enzyme in mammalian tissues that catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a potentially important regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems, and inhibitors of ADK could play an important pharmacologic role in increasing intravascular adenosine concentrations and acting as inflammatory agents (summary by Spychala et al., 1996).CLONING
Spychala et al. (1996) obtained full-length cDNA clones encoding catalytically active ADK from lymphocyte, placental, and liver cDNA libraries. On Northern blots of all tissues examined, they identified mRNA species of 1.3 and 1.8 kb, attributable to alternative polyadenylation sites at the 3-prime end of the gene. The encoded protein consisted of 345 amino acids with a calculated molecular size of 38.7 kD and without any sequence similarities to other well-characterized mammalian nucleoside kinases. In contrast, 2 regions were identified with significant sequence identity to microbial ribokinase and fructokinases and a bacterial inosine/guanosine kinase. Thus, ADK is a structurally distinct mammalian nucleoside kinase that appears to be akin to sugar kinases of microbial origin. McNally et al. (1997) also cloned human cDNAs encoding adenosine kinase. They found cDNAs encoding both the 345-amino acid form and a 362-amino acid form of the enzyme. These 2 alternately spliced forms differed only at the 5-prime end. When expressed, both isoforms of the enzyme phosphorylated adenosine with identical kinetics and both required Mg2+ for activity.MAPPING
The structural gene for this enzyme was tentatively assigned to chromosome 10 by somatic cell hybrid studies (Klobutcher et al., 1976). By the principle of gene dosage, Francke and Thompson (1979) concluded by exclusion that ADK must be in the region 10q11-10q24. In a case of trisomy 10p, Snyder et al. (1984) found normal levels of ADK.MOLECULAR GENETICS
By exome sequencing, Bjursell et al. (2011) identified a homozygous mutation in the ADK gene (102750.0001) in 2 Swedish sibs with severe developmental delay, mild liver dysfunction, and persistent hypermethioninemia due to adenosine kinase deficiency (614300). Subsequent analysis of this gene in Malaysian patients with a similar phenotype revealed 2 different homozygous mutations in the ADK gene (102750.0002 and 102750.0003) in 2 families. The phenotype was characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy); homocysteine was typically normal. Bjursell et al. (2011) concluded that the phenotype resulted from a combination of direct adenosine toxicity, a defect in the regulation of adenosine, and disruption of a wide range of methyltransferase reactions.ANIMAL MODEL
Neonatal hepatic steatosis (228100) is a fatal condition characterized by rapid microvesicular fat infiltration and enlargement of the liver, which shows a pale and yellowish coloration. Microvesicular fat infiltration, liver failure, coma, and death are considered to be a ... More on the omim web site
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 102750 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed