Fructosamine-3-kinase (FN3K)
The protein contains 309 amino acids for an estimated molecular weight of 35171 Da.
Fructosamine-3-kinase involved in protein deglycation by mediating phosphorylation of fructoselysine residues on glycated proteins, to generate fructoselysine-3 phosphate (PubMed:11016445, PubMed:11522682, PubMed:11975663). Fructoselysine-3 phosphate adducts are unstable and decompose under physiological conditions (PubMed:11522682, PubMed:11975663). Involved in intracellular deglycation in erythrocytes (PubMed:11975663). Involved in the response to oxidative stress by mediating deglycation of NFE2L2/NRF2, glycation impairing NFE2L2/NRF2 function (By similarity). Also able to phosphorylate psicosamines and ribulosamines (PubMed:14633848). (updated: Oct. 16, 2019)
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.
- 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.
- 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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No binding partner found
The reference OMIM entry for this protein is 608425
Fructosamine 3-kinase
Fn3k
DESCRIPTION
FN3K catalyzes phosphorylation of fructosamines formed by glycation, the nonenzymatic reaction of glucose with primary amines followed by Amadori rearrangement. Phosphorylation of fructosamines may initiate metabolism of the modified amine and result in deglycation of glycated proteins (Delpierre et al., 2000).CLONING
Delpierre et al. (2000) purified FN3K from erythrocyte extracts. By partial sequencing of tryptic peptides, followed by examination of an EST database and PCR amplification, they cloned FN3K from a kidney cDNA library. They cloned mouse Fn3k from a brain cDNA library. Both predicted proteins contain 309 amino acids and have calculated molecular masses of 35 kD. Human and mouse FN3K share 86% amino acid identity. Purified FN3K showed an apparent molecular mass of 35 kD by SDS-PAGE. Using RT-PCR, Conner et al. (2004) detected variable FN3K expression in all human tissues examined, with highest levels in brain, kidney, spinal cord, and heart.GENE FUNCTION
Delpierre et al. (2000) demonstrated that purified FN3K catalyzed ATP-dependent phosphorylation of a synthetic fructosamine, 1-deoxy-1-morpholinofructose (DMF). Recombinant mouse and human FN3K, expressed in E. coli, catalyzed phosphorylation of DMF, fructoselysine, fructoseglycine, and fructose in order of decreasing affinity. They also phosphorylated glycated lysozyme, but not unmodified lysozyme. In addition to ATP, FN3K was able to utilize GTP, CTP, and UTP as phosphate donors. Nuclear magnetic resonance analysis showed that the phosphate was bound to the third carbon of the 1-deoxyfructose moiety.GENE STRUCTURE
Collard et al. (2003) determined that the FN3K gene contains 6 exons. Conner et al. (2004) found that the promoter region of the FN3K gene has a high GC content, but no TATA or CAAT boxes. It also has 2 putative NFKB (see 164011)-binding sites.MAPPING
By genomic sequence analysis and FISH, Collard et al. (2003) mapped the FN3K gene to chromosome 17q25. They identified 2 FN3K pseudogene fragments on chromosome 22. ... More on the omim web site
Oct. 27, 2019: 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 608425 was added.