Cytokine receptor-like factor 3 (CRLF3)
The protein contains 442 amino acids for an estimated molecular weight of 49766 Da.
May play a role in the negative regulation of cell cycle progression. (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.
- 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.
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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| Variant | Description |
|---|---|
| dbSNP:rs3764418 | |
| dbSNP:rs11867457 |
Biological Process
G1/S transition of mitotic cell cycle
Negative regulation of cell growth
Positive regulation of cell cycle arrest
Positive regulation of receptor signaling pathway via JAK-STAT
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription, DNA-templated
The reference OMIM entry for this protein is 614853
Cytokine receptor-like factor 3; crlf3
Cytokine receptor-related protein 4; cytor4
Cytokine receptor-like molecule 9; crlm9
Creme9
CLONING
Yang et al. (2009) cloned 2 CRLF3 splice variants from a K562 cDNA library. The deduced 438- and 442-amino acid proteins, which the authors called p48.2 and p48.6, respectively, differ only by the absence or presence of 4 N-terminal amino acids. CRLF3 contains a fibronectin (135600) type III domain, which includes an palindromic RGD repeat, a WSPWS motif, and a tyrosine sulfation site, as well as an N-glycosylation site. Database analysis revealed CRLF3 orthologs in several vertebrate species, with highest conservation in the fibronectin type III domain, tyrosine sulfation site, and RGDGR motif. Mouse and human CRLF3 share 92% amino acid identity. RT-PCR detected variable CRLF3 expression in most human embryonic and adult tissues and cell lines examined. Fluorescence- or epitope-tagged CRLF3 was expressed in the cytoplasm of transfected cells.GENE FUNCTION
Yang et al. (2009) found that overexpression of CRLF3 in synchronized HEK293T cells induced cell cycle arrest at G0/G1 phase. Conversely, knockdown of CRLF3 via small interfering RNA decreased the G0/G1-phase cell population and increased the S-phase cell population. RT-PCR and Western blot analysis revealed that CRLF3 significantly upregulated cyclin D1 (CCND1; 168461), cyclin D3 (CCND3; 123834), and p27 (CDKN1B; 600778) expression. CRLF3-mediated cyclin D1 upregulation appeared to involve phosphorylated STAT3 (102582).GENE STRUCTURE
Yang et al. (2009) determined that the CRLF3 gene contains 13 exons and spans 73 kb. Exons 1 and 5 contain translational start sites. The promoter region contains a TATA box.MAPPING
By genomic sequence analysis, Jenne et al. (2001) identified the CRLF3 gene, which they called CYTOR4, on chromosome 17q11.2, near the NF1 gene (613113). ... 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 614853 was added.