UMP-CMP kinase (CMPK1)
The protein contains 196 amino acids for an estimated molecular weight of 22222 Da.
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity. (updated: Oct. 10, 2018)
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.
(right-click above to access to more options from the contextual menu)
No binding partner found
Biological Process
'de novo' pyrimidine nucleobase biosynthetic process
CDP biosynthetic process
Nucleobase-containing small molecule interconversion
Nucleoside diphosphate phosphorylation
Nucleoside triphosphate biosynthetic process
Purine nucleotide metabolic process
Pyrimidine ribonucleotide biosynthetic process
UDP biosynthetic process
The reference OMIM entry for this protein is 191710
Cytidine monophosphate (ump-cmp) kinase 1, cytosolic; cmpk1
Cytidine monophosphate kinase; cmpk
Cytidylate kinase; cmk
Uridine monophosphate/cytidine monophosphate kinase
Ump/cmp kinase
Ump/cmpk
Uridine monophosphate kinase; umpk; umk
DESCRIPTION
Uridine monophosphate (UMP)/cytidine monophosphate (CMP) kinase (EC 2.7.4.4) catalyzes the phosphoryl transfer from ATP to UMP, CMP, and deoxy-CMP (dCMP), resulting in the formation of ADP and the corresponding nucleoside diphosphate. These nucleoside diphosphates are required for cellular nucleic acid synthesis (Liou et al., 2002).CLONING
By searching an EST database for sequences similar to pig UMP/CMP kinase, Van Rompay et al. (1999) identified and cloned human UMP/CMP kinase. The longest deduced protein contains 228 amino acids and has a calculated molecular mass of 26 kD. However, translation likely begins at the second initiation methionine, resulting in a protein of 196 amino acids. UMP/CMP kinase has a glycine-rich nucleoside triphosphate-binding region followed by a nucleoside monophosphate-binding site in its N-terminal half and a lid domain in its C-terminal half. Northern blot analysis detected a 3.9-kb transcript expressed in all tissues examined, with highest expression in pancreas, skeletal muscle, and liver. Fluorescence-tagged UMP/CMP kinase localized to both the cytosol and nucleus of transfected Chinese hamster ovary cells. By EST database analysis and PCR of a human epidermoid carcinoma cell line cDNA library, Liou et al. (2002) cloned UMP/CMP kinase. Western blot analysis detected UMP/CMP kinase in all human cell lines examined. The endogenous enzyme appeared as a single protein that comigrated with the 196-amino acid form expressed in transfected HeLa cells. Liou et al. (2002) concluded that the shorter form is the endogenously translated protein.GENE FUNCTION
Van Rompay et al. (1999) characterized the enzymatic activity of recombinant UMP/CMP kinase. The ribonucleotides UMP and CMP were both efficiently phosphorylated, and lower activity was detected for dCMP, dUMP, AMP, and dAMP. UMP/CMP kinase did not phosphorylate other nucleotide monophosphates. The addition of a reducing agent increased phosphorylation of dCMP 21-fold, but it had no effect on other substrates. Overall, CMP was the best substrate. Monophosphate derivatives of several anticancer nucleosides were also substrates for UMP/CMP kinase. Liou et al. (2002) found that the 228- and 196-amino acid forms of UMP/CMP kinase showed identical enzymatic activity. By examining the kinetics of the phosphorylation of D- and L-forms of dideoxyCMP, they determined that UMP/CMP kinase lacks stereoselectivity. Reducing agents activated UMP/CMP kinase in a dose-dependent manner. ATP and dATP were the best phosphate donors, whereas CTP was the poorest. dGTP and TTP were efficient phosphate donors for UMP and dCMP substrates, but not for CMP. There was strong feedback inhibition, with CTP inhibiting UMP phosphorylation by 80% and dCMP phosphorylation by 60%.BIOCHEMICAL FEATURES
Segura-Pena et al. (2004) reported the crystal structure of the substrate-free open form of UMP/CMP kinase and compared it to the closed state previously reported for the similar D. discoideum UMP/CMP kinase. They observed a classic example of induced fit, where substrate-induced conformational changes in hinge residues result in rigid body movements of functional domains to form the catalytically competent state. The lid domain undergoes closure upon binding of substrates, bringing several catalytic residues in close proximity with the phosphate groups of both substrates.MAPPING
Giblett et al. (1975) showed that UMPK and Rh ( ... More on the omim web site
July 1, 2020: Protein entry updated
Automatic update: OMIM entry 191710 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).