Serine/threonine-protein kinase TAO3 (TAOK3)
The protein contains 898 amino acids for an estimated molecular weight of 105406 Da.
Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF). (updated: March 4, 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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Activation of MAPKK activity
Activation of protein kinase activity
Cellular response to DNA damage stimulus
DNA repair
MAPK cascade
Mitotic G2 DNA damage checkpoint signaling
Negative regulation of JNK cascade
Negative regulation of protein kinase activity
Nervous system development
Neuron projection morphogenesis
Positive regulation of JNK cascade
Positive regulation of JUN kinase activity
Positive regulation of stress-activated MAPK cascade
Protein autophosphorylation
Protein phosphorylation
Regulation of apoptotic process
Regulation of mitotic cell cycle
Signal transduction by protein phosphorylation
Stress-activated protein kinase signaling cascade
The reference OMIM entry for this protein is 616711
Tao kinase 3; taok3
Jnk/sapk-inhibitory kinase; jik
Dendritic cell-derived protein kinase; dpk
DESCRIPTION
Mitogen-activated protein kinase (MAPK) cascades, including the ERK (see 601795), JNK/SAPK (see 601158), and p38 (see 600289) pathways, are the major signaling systems that link extracellular signals to intracellular responses. Thousand and one amino acid (TAO) kinases, such as TAOK3, are Ste20-related MAP3Ks (summary by Zhang et al., 2000).CLONING
By screening a human M426 fibroblast expression library with the bacterially expressed SH3 domain of eps8, Tassi et al. (1999) identified a TAOK3 cDNA, which the authors called JIK. The deduced 898-amino acid protein has a calculated molecular mass of 106 kD. The N-terminus encompasses a kinase domain including all 11 subdomains characteristic of serine/threonine kinases. The kinase domain shares sequence homology with members of the GCK (603166) subfamily of STE20-like kinases with an N-terminal catalytic domain and no p21-binding domain. The protein shares 57% sequence identity in the kinase domain with human STK3 (605030) and STK4 (604965) and 63% overall sequence identity with C. elegans Sulu. Northern blot analysis detected ubiquitous expression of a 4.4-kb transcript at similar levels in most tissues. Zhang et al. (2000) cloned TAOK3, which they called DPK, from a dendritic cell cDNA library. In addition to the domains described by Tassi et al. (1999), they identified a zipper-binding and an ATP-binding region. They pointed out that the kinase domain exhibits significant homology to MAPKKKs, e.g., MAP3K1 (600982) and MAP3K2 (609487). Northern blot analysis detected ubiquitous expression of TAOK3, with highest expression in kidney, heart, and skeletal muscle. Expression was also detected in many leukemia cell lines, but not in colorectal, lung, or skin cancer cell lines. Raman et al. (2007) showed that TAOK3, like TAOK1 (610266) and TAOK2 (613199), has SQ/TQ sites in its C-terminal domain, which serve as substrates for ATM and ATR phosphorylation.MAPPING
Robbins (2015) mapped the TAOK3 gene to chromosome 12q24.23 based on alignment of the TAOK3 sequence (GenBank GENBANK AF135158) with the genomic sequence (GRCh38).GENE FUNCTION
Tassi et al. (1999) found that TAOK3 activity and autophosphorylation was potently reduced after EGF (131530) stimulation. Coexpression of TAOK3 with JNK/SAPK in COS-7 cells showed that TAOK3 was unable to activate JNK/SAPK but reduced its basal activity. When TAOK3 and JNK were coexpressed in the presence of EGF, JNK activation by EGF was reduced. When TAOK3 and JNK were coexpressed in the presence of potent activators such as anisomycin and UV light, JNK activation was not affected by TAOK2. Coexpression studies with TAOK3 and the signaling kinases ERK2 (176948), ERK5 (602521), ERK6 (602399), p38 (600289), and SAPK4 (602899) showed that TAOK3 does not activate or have a significant negative effect on their enzymatic activity. Using an in vitro kinase phosphorylation assay in mouse NIH3T3 fibroblasts, Zhang et al. (2000) found that overexpression of DPK could activate both the Erk1 (601795)/Erk2 pathway and the JNK/SAPK pathway in a dose-dependent manner, but did not affect the p38 pathway. Raman et al. (2007) expressed dominant-negative TAOK3 mutant protein in HEK293 and HeLa cells that were treated with hydroxyurea, ionizing radiation, or UV light to induce the DNA damage response. P38 activation normally induced by these agents was reduced by 50% or more in the presence of the mutant TAOK3. TAOK3 knock ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616711 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated