Exportin-2 (CSE1L)
The protein contains 971 amino acids for an estimated molecular weight of 110417 Da.
Export receptor for importin-alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates (cargos) have been released into the nucleoplasm. In the nucleus binds cooperatively to importin-alpha and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the importin-alpha from the export receptor. CSE1L/XPO2 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. (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.
- 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.
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:rs2229042 | |
| a colorectal cancer sample; somatic mutation | |
| dbSNP:rs3505 |
Biological Process
Apoptotic process
Cell population proliferation
Intracellular protein transport
Protein export from nucleus
Protein import into nucleus
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Membrane
Nuclear envelope
Nucleoplasm
Nucleus
The reference OMIM entry for this protein is 601342
Chromosome segregation 1-like; cse1l
Cellular apoptosis susceptibility; cas
Chromosome segregation gene cse1, yeast, homolog of
Cse1, yeast, homolog of
CLONING
Brinkmann et al. (1995) cloned several HeLa cell cDNAs that render MCF-7 breast cancer cells resistant to immunotoxins. Brinkmann et al. (1995) found that one of these cDNAs contains a portion of the human homolog of the yeast chromosome segregation gene CSE1. They noted that an antisense fragment of the human homolog had conferred immunotoxin resistance. They cloned the full-length cDNA for the human homolog and designated it the 'cellular apoptosis susceptibility' (CAS) gene. Northern blot analysis showed that the 3.1-kb CAS mRNA was expressed preferentially in proliferating cells. On Western blots, the predicted 971-amino acid protein migrated as an approximately 100-kD protein; its expression correlated with cell proliferation.MAPPING
By fluorescence in situ hybridization, Brinkmann et al. (1996) mapped the CAS gene to 20q13. This region had been known to harbor amplifications that correlate with aggressive breast cancer. Brinkmann et al. (1996) used Southern hybridization with a CAS cDNA fragment and fluorescence in situ hybridization with a P1 clone containing the CAS gene and found elevated copy numbers of CAS in a leukemia cell line, 3 of 4 colon cell lines, and 3 of 7 breast cancer cell lines. In 2 of these cell lines (the leukemia and a colon cancer), they attributed elevated CAS copy number to additional copies of chromosome 20.GENE FUNCTION
Brinkmann et al. (1996) noted that CAS may have a dual function in mammalian cells, 1 in apoptosis and another in cell proliferation. Brinkmann et al. (1996) observed that CAS antisense RNA can interfere with apoptosis mediated by tumor necrosis factor-alpha (191160) and beta (153440) and by ADP-ribosylating toxins, suggesting that CAS may play a role in selected pathways of apoptosis. Proteins that carry a nuclear localization signal (NLS) are transported into the nucleus by the importin-alpha/-beta heterodimer. Importin-alpha (see 600685 and 600686) binds the NLS, while importin-beta (see 602008) mediates translocation through the nuclear pore complex. After translocation, RanGTP (see RANGAP1; 602362), which has a high predicted concentration in the nucleus and a low predicted concentration in the cytoplasm, binds importin-beta and displaces importin-alpha. Importin-alpha must then be returned to the cytoplasm, leaving the NLS protein behind. Kutay et al. (1997) reported that the CAS protein mediates importin-alpha reexport. CAS binds strongly to importin-alpha only in the presence of RanGTP, forming an importin-alpha/CAS/RanGTP complex. Importin-alpha is released from this complex in the cytoplasm by the combined action of RANBP1 (601180) and RANGAP1. CAS binds preferentially to NLS-free importin-alpha, explaining why import substrates stay in the nucleus. In a 'Minireview,' Ullman et al. (1997) summarized existing research relating to nuclear export receptors. Brinkmann (1998) provided a review of the role of CAS in proliferation, apoptosis, and cancer.BIOCHEMICAL FEATURES
- Crystal Structure Matsuura and Stewart (2004) presented the 2.0-angstrom crystal structure of the nuclear export complex formed by exportin Cse1p complexed with its cargo Kap60p (importin-alpha; see 600685) and RanGTP (see 602362), thereby providing a structural framework for understanding nuclear protein export and the different functions of RanGTP in export and import. In the complex, Cse1p coils around both RanGTP and Kap60p, stabilizing the RanGTP-state an ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601342 was added.