UMP-CMP kinase 2, mitochondrial (CMPK2)
The protein contains 449 amino acids for an estimated molecular weight of 49448 Da.
May participate in dUTP and dCTP synthesis in mitochondria. Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP; CMP and UMP are poor substrates. May be involved in mtDNA depletion caused by long term treatment with ddC or other pyrimidine analogs. Also displays broad nucleoside diphosphate kinase activity. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- 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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| Variant | Description |
|---|---|
| dbSNP:rs6712141 |
No binding partner found
The reference OMIM entry for this protein is 611787
Cytidine monophosphate (ump-cmp) kinase 2, mitochondrial; cmpk2
Cytidylate kinase 2
Uridine monophosphate/cytidine monophosphate 2
Ump/cmp kinase 2
Ump/cmpk2
DESCRIPTION
Mitochondrial UMP-CMP kinase (EC 2.7.2.14) is a component of the salvage pathway for nucleotide synthesis. Other enzymes of the salvage pathway include thymidine kinase-2 (TK2; 188250), deoxynucleotidase-2 (NT5M; 605292), deoxyguanosine kinase (DGUOK; 601465), adenylate kinase-2 (AK2; 103020), adenylate kinase-3 (AK3; 609290), adenylate kinase-3-like-1 (AK3L1; 103030), and nucleoside diphosphate kinase (NME4; 601818) (Xu et al., 2008).CLONING
Xu et al. (2008) cloned a full-length human homolog of the mouse Cmpk2 gene. The mouse gene had originally been reported as a thymidylate kinase (DTYMK; 188435) family member inducible with lipopolysaccharide (LPS) and designated TYKi by Lee and O'Brien (1995). The deduced 449-amino acid human CMPK2 protein contains a thymidylate kinase domain and is predicted to have an ATP/GTP-binding motif, a LID domain, an adenine-base-binding loop, a catalytic site, and a possible substrate-binding site. The first 22 amino acids are a mitochondrial targeting signal. A GFP-tagged recombinant molecule localized CMPK2 to mitochondria. Of several cancer lines tested, Northern blot analysis detected the 3.3-kb CMPK2 mRNA in only chronic myelogenous leukemia K-562 and lymphoblastic leukemia MOLT-4 cells.GENE FUNCTION
Although the protein sequence of CMPK2 is more closely related to thymidylate kinase than to CMPK1 (191710), Xu et al. (2008) detected no thymidylate kinase activity from highly purified recombinant CMPK2 expressed in insect cells or in E. coli. Recombinant CMPK2 phosphorylated dUMP, dCMP, CMP, and UMP, with a preference for dUMP and dCMP compared to the ribonucleotides CMP and UMP. CMPK2 also showed a 35-fold preference for dUMP over dCMP. Xu et al. (2008) concluded that CMPK2 is the first pyrimidine nucleoside monophosphate kinase identified in human mitochondria.MAPPING
Xu et al. (2008) stated that the CMPK2 gene maps to chromosome 2p25.2. ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611787 was added.