Guanylate kinase (GUK1)
The protein contains 197 amino acids for an estimated molecular weight of 21726 Da.
Catalyzes the phosphorylation of GMP to GDP. Essential enzyme for recycling GMP and indirectly, cyclic GMP (cGMP) (PubMed:31201273). Involved in the cGMP metabolism in photoreceptors (By similarity). It may also have a role in the survival and growth progression of some tumors (PubMed:31201273). In addition to its physiological role, GUK1 is essential for convert prodrugs used for the treatment of cancers and viral infections into their pharmacologically active metabolites, most notably acyclovir, ganciclovir, and 6-thioguanine and its closely related analog 6-mercaptopurine (PubMed:197968, PubMed:6248551, PubMed:6306664). (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.
- 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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No binding partner found
Biological Process
ATP metabolic process
DATP metabolic process
DGDP biosynthetic process
DGMP metabolic process
Drug metabolic process
GDP biosynthetic process
GDP-mannose metabolic process
Glycoprotein transport
GMP metabolic process
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Nucleotide phosphorylation
Purine nucleotide metabolic process
Small molecule metabolic process
Xenobiotic metabolic process
The reference OMIM entry for this protein is 139270
Guanylate kinase 1; guk1
Gmp kinase; gmk
Atp:gmp phosphotransferase
DESCRIPTION
Guanylate kinase (EC 2.7.4.8) catalyzes the phosphorylation of either GMP to GDP or dGMP to dGDP and is an essential enzyme in nucleotide metabolism pathways (summary by Brady et al., 1996).CLONING
Brady et al. (1996) cloned human and mouse cDNAs of GUK1. They reported that the human gene predicts a protein of 197 amino acids with a molecular mass of 21.7 kD. They found that the 1-kb GUK1 transcript was ubiquitously expressed.GENE FUNCTION
Brady et al. (1996) stated that the guanylate kinases are targets for cancer chemotherapy and are inhibited by the antitumor drug 6-thioguanine. They published a computer model of GUK1 tertiary structure designed to be used in the development of chemotherapy drugs.MAPPING
From cell hybridization studies, Meera Khan et al. (1974) concluded that the GUK1 gene may be on chromosome 1. Meera Khan (1977) stated that the genetic independence of GUK1 and GUK2 (139280) has not been established; it might be a situation like that of fumarate hydratase in which cytosolic and mitochondrial forms are encoded by the same gene. Dallapiccola et al. (1980) found increased red cell GUK in a patient with a duplication of 1q31-q43. By fluorescence in situ hybridization, Fitzgibbon et al. (1996) mapped the GUK1 gene to 1q32-q41. ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 139270 was added.