Ragulator complex protein LAMTOR3 (LAMTOR3)
The protein contains 124 amino acids for an estimated molecular weight of 13623 Da.
As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- 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.
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Biological Process
Activation of MAPKK activity
Cell cycle arrest
Cellular protein localization
Cellular response to amino acid starvation
Cellular response to amino acid stimulus
MAPK cascade
Neutrophil degranulation
Positive regulation of TOR signaling
Protein localization to cell junction
Regulation of macroautophagy
The reference OMIM entry for this protein is 603296
Late endosomal/lysosomal adaptor, mitogen-activated protein kinase and mammalian target of rapamycin activator 3; lamtor3
Late endosomal/lysosomal adaptor, mapk and mtor activator 3
Mek partner 1; mp1
Mapbp
Mitogen-activated protein kinase ki
CLONING
Schaeffer et al. (1998) used a 2-hybrid screen with MEK1 (176872) as bait to identify nonenzymatic components of the extracellular signal-regulated kinase (ERK) cascade that might be important in regulating its activity. The ERK cascade is one of several evolutionarily conserved mitogen-activated protein (MAP) kinase cascades important in the regulation of growth, apoptosis, and differentiation. The MAP kinases ERK1 (601795) and ERK2 (176948) are activated by the MAP kinase kinases MEK1 or MEK2 (601263). MEKs, in turn, are activated by members of the Raf family, e.g., RAF1 (164760). Schaeffer et al. (1998) identified a 13.5-kD protein, which they called MP1 (MEK partner-1). RNA blot analysis of various mouse tissues showed similar amounts of 1.4- to 1.5-kb MP1 transcript in heart, brain, lung, liver, muscle, and kidney, and smaller amounts in spleen and testis. Immunoblot analysis detected MP1 protein in various cell lines.GENE FUNCTION
Schaeffer et al. (1998) found that MP1 bound specifically to MEK1 and ERK1 and facilitated their activation. When overexpressed in cultured cells, MP1 enhanced activation of ERK1 and activation of a reporter driven by the transcription factor ELK1 (311040). Expression of MP1 in cells increased binding of ERK1 to MEK1. MP1 apparently functions as an adaptor to enhance the efficiency of the MAP kinase cascade.MAPPING
Gross (2012) mapped the LAMTOR3 gene to chromosome 4q23 based on an alignment of the LAMTOR3 sequence (GenBank GENBANK AF130115) with the genomic sequence (GRCh37). ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 603296 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).