Methylosome subunit pICln (CLNS1A)
The protein contains 237 amino acids for an estimated molecular weight of 26215 Da.
Involved in both the assembly of spliceosomal snRNPs and the methylation of Sm proteins (PubMed:21081503, PubMed:18984161). Chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. May also indirectly participate in cellular volume control by activation of a swelling-induced chloride conductance pathway. (updated: May 23, 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.
- 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.
This protein is annotated as membranous in Gene Ontology.
Biological Process
Cell volume homeostasis
Chloride transport
Gene expression
NcRNA metabolic process
Spliceosomal snRNP assembly
The reference OMIM entry for this protein is 602158
Chloride channel, nucleotide sensitive, 1a; clns1a
Chloride conductance regulator, volume sensitive; icln
CLONING
Anguita et al. (1995) cloned a novel gene encoding the chloride channel I(Cln) from a human ocular ciliary epithelial cell cDNA library. The gene encodes a 237-amino acid polypeptide that is over 90% identical to rat and canine I(Cln). The predicted protein contains 4 putative transmembrane domains. By Northern blot analysis, Nagl et al. (1996) found that the gene is expressed as an approximately 1.7-kb message in a variety of human tissues. Buyse et al. (1996) independently cloned I(Cln) from a leukemic cell line cDNA library and leukocyte RNA. Although I(Cln) has a predicted molecular mass of 26.2 kD, I(Cln) protein extracted from human endothelial cell lines migrated at 40 kD on SDS-PAGE. Buyse et al. (1996) suggested that anomalous migration was due to the high number of acidic amino acids in I(Cln), which has a pI of 3.8.GENE FUNCTION
Schwartz et al. (1997) cloned I(Cln) from human reticulocyte cDNA. I(Cln) protein from red blood cell ghost membranes migrated as 2 bands, 37 and 43 kD, on SDS-PAGE. Schwartz et al. (1997) immunolocalized I(Cln) to the red blood cell membrane and, by the yeast 2-hybrid system, demonstrated that it formed stable complexes with beta-actin (102630). The authors suggested that I(Cln) is involved in chloride transport and volume regulation in red blood cells.GENE STRUCTURE
Nagl et al. (1996) cloned the genomic DNA of the CLNS1A gene and showed that the gene comprises several exons spanning 19 kb of the genome.MAPPING
Nagl et al. (1996) used fluorescence in situ hybridization to localize the I(Cln) gene to chromosome 11q13.5-q14.1. Schwartz et al. (1997) mapped the I(Cln) gene to 11q13 by fluorescence in situ hybridization, and confirmed this map position by finding homologous sequence contained within a Human Gene Map marker from that region. - PSEUDOGENE By PCR strategies, Nagl et al. (1996) mapped an intronless copy of the CLNS1A gene, which they termed CLNS1B, to chromosome 6q13. Nagl et al. (1996) stated that further testing would reveal whether CLNS1B is a pseudogene or is functionally expressed. ... More on the omim web site
May 26, 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602158 was added.