Calcium-binding protein 39 (CAB39)
The protein contains 341 amino acids for an estimated molecular weight of 39869 Da.
Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1. (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.
- 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.
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Biological Process
Activation of protein kinase activity
Cell cycle arrest
Cellular hypotonic response
Insulin receptor signaling pathway
Intracellular signal transduction
Negative regulation of potassium ion transmembrane transport
Negative regulation of potassium ion transmembrane transporter activity
Neutrophil degranulation
Obsolete negative regulation of rubidium ion transmembrane transporter activity
Obsolete negative regulation of rubidium ion transport
Peptidyl-serine phosphorylation
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of peptidyl-threonine phosphorylation
Positive regulation of protein serine/threonine kinase activity
Protein heterooligomerization
Response to activity
Response to thyroid hormone
Signal transduction
Signal transduction by protein phosphorylation
The reference OMIM entry for this protein is 612174
Calcium-binding protein 39; cab39
Mo25-alpha
CLONING
By searching databases using peptide fragments of proteins that interacted with the serine/threonine protein kinase LKB1 (STK11; 602216) in HeLa cells, Boudeau et al. (2003) identified CAB39, which they designated MO25-alpha. The deduced 341-amino acid protein shares a high degree of conservation with its C. elegans and Drosophila orthologs. Northern blot analysis detected a 4.2-kb MO25-alpha transcript in all tissues examined, with highest expression in skeletal muscle. Western blot analysis detected MO25-alpha in most tissues and cell lines examined. Endogenous MO25-alpha in HeLa cells had an apparent molecular mass of 40 kD by SDS-PAGE.GENE FUNCTION
By immunoprecipitation analysis of human and rat cells, Boudeau et al. (2003) showed that MO25-alpha associated with STRAD-alpha (608626) and LKB1. Cotransfection and mutation analysis revealed that MO25-alpha interacted directly with STRAD-alpha rather than with LKB1, and the interaction required the last 3 residues of STRAD-alpha. MO25-alpha also interacted with STRAD-beta (ALS2CR2; 607333) in a complex with LKB1. MO25-alpha and STRAD-alpha anchored LKB1 in the cytoplasm, excluding it from the nucleus. Moreover, MO25-alpha enhanced formation of LKB1-STRAD-alpha complexes in vivo and stimulated LKB1 catalytic activity about 10-fold. Boudeau et al. (2003) concluded that MO25-alpha may function as a scaffolding component of the LKB1-STRAD complex and regulate LKB1 activity and cellular localization. Using mutagenesis, Boudeau et al. (2004) identified 2 binding sites on opposite surfaces of MO25-alpha that were required for assembly of the MO25-alpha-STRAD-alpha-LKB1 complex. Denning et al. (2012) identified a mechanism of cell extrusion that is caspase-independent and that can eliminate a subset of the C. elegans cells programmed to die during embryonic development. In wildtype animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all 4 C. elegans caspase genes, these cells were eliminated by being extruded from the developing embryo into the extraembryonic space of the egg. The shed cells showed apoptosis-like cytologic and morphologic characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. Denning et al. (2012) described a kinase pathway required for cell extrusion involving Par4, Strd1, and Mop25.1/25.2, the C. elegans homologs of the mammalian tumor suppressor kinase LKB1 (602216) and its binding partners STRAD-alpha (608626) and MO25-alpha. The AMPK-related kinase Pig1, a possible target of the Par4-Strd1-Mop25 kinase complex, is also required for cell shedding. Pig1 promotes shed cell detachment by preventing the cell surface expression of cell adhesion molecules. Denning et al. (2012) concluded that their findings revealed a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death.BIOCHEMICAL FEATURES
- Crystal Structure Zeqiraj et al. (2009) described the structure of the core heterotrimeric LKB1-STRAD-alpha-MO25-alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRAD-alpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRAD-alpha and MO25-alpha promote the active conformation of LKB1, which is stabilized by MO25-alpha interacting with the LKB1 activation loop. Zeqiraj et al. (2009) suggested that thi ... 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 612174 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed