MAP/microtubule affinity-regulating kinase 3 (MARK3)
The protein contains 753 amino acids for an estimated molecular weight of 84489 Da.
Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). (updated: June 20, 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.
- 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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| Variant | Description |
|---|---|
| empty | |
| dbSNP:rs56305318 | |
| dbSNP:rs10137161 | |
| VIPB |
Biological Process
Establishment of cell polarity
Intracellular signal transduction
MAPK cascade
Microtubule cytoskeleton organization
Negative regulation of hippo signaling
Peptidyl-serine autophosphorylation
Peptidyl-serine phosphorylation
Positive regulation of protein binding
Protein phosphorylation
The reference OMIM entry for this protein is 602678
Map/microtubule affinity-regulating kinase 3; mark3
Microtubule-associated protein/microtubule affinity-regulating kinase 3
Cdc25c-associated protein kinase 1; ctak1
Par1, c. elegans, homolog of, a; par1a
CLONING
MARK proteins are involved in the specific phosphorylation of microtubule-associated proteins for tau (157140), MAP2 (157130), and MAP4 (157132). MARK3 was originally identified as a marker (KP78) that was induced by treatment with DNA damaging agents, and loss of MARK3 was found with carcinogenesis in the pancreas (Parsa, 1988). MARK3 may be involved in cell cycle regulation, and alterations in the MARK3 gene may lead to carcinogenesis. Peng et al. (1998) cloned a full-length HeLa cell cDNA encoding MARK3, which they called CTAK1. By Northern blot analysis, CTAK1 was expressed as 3.1- and 3.8-kb transcripts in all human tissues examined; an additional 3.0-kb transcript was observed in heart. The predicted 729-amino acid CTAK1 protein belongs to the AMPK (e.g., 602739) subfamily of protein kinases. Members of this subfamily are characterized by a conserved N-terminal kinase domain, a divergent C-terminal region, and a conserved region of about 40 amino acids at their extreme C-termini, which end with an ELKL (glutamate-leucine-lysine-leucine) domain. CTAK1 protein from HeLa cell lysates resolved as a doublet of approximately 78 and 80 kD in Western blot and immunoprecipitation analyses. Indirect immunofluorescence detected CTAK1 in the cytoplasm but not the nucleus of HeLa cells. The authors demonstrated that CTAK1 binds to CDC25C (157680) and phosphorylates CDC25C on serine-216 in vitro and in vivo. Using Western blot analysis, Lennerz et al. (2010) found that Par1a was expressed at variable levels in all mouse tissues examined. Database analysis suggested the presence of 5 Par1a splice variants encoding proteins of 659 to 753 amino acids.BIOCHEMICAL FEATURES
Muller et al. (2001) showed that KSR1 (601132) translocates from the cytoplasm to the cell surface in response to growth factor treatment and that this process is regulated by CTAK1. CTAK1 constitutively associates with mammalian KSR1 and phosphorylates ser392 to confer 14-3-3 binding and cytoplasmic sequestration of KSR1 in unstimulated cells. In response to signal activation, the phosphorylation state of ser392 is reduced, allowing the KSR1 complex to colocalize with activated RAS and RAF1 (164760) at the plasma membrane, thereby facilitating the phosphorylation reactions required for the activation of MEK and MAPK (see 176872).MAPPING
Ono et al. (1997) used fluorescence in situ hybridization to map the MARK3 gene to 14q32.3.ANIMAL MODEL
Lennerz et al. (2010) obtained Par1a -/- mice at less than mendelian ratios. Those that survived were viable and developed normally, but became hypermetabolic and showed reduced body weight, adiposity, and hypofertility compared with wildtype. Par1a -/- mice on a high-fat diet exhibited profound resistance to development of glucose intolerance, weight gain, and hepatic steatosis. Upon short-term starvation, livers of Par1a -/- mice exhibited defects in both glycogen storage and glucose mobilization, with depletion of lipid and glycogen stores, upregulation of glycogen synthase (GYS1; 138570), and activation of autophagy. This phenotype partly overlapped that displayed by Par1b -/- mice. Double knockout of Par1a and Par1b in mice was embryonic lethal. At least 1 allele of either Par1a or Par1b was necessary for viability, but mice expressing only 1 Par1 allele were not healthy, and a high proportion died shortly after birth. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
July 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: 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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602678 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed