C-C chemokine receptor-like 2 (CCRL2)
The protein contains 344 amino acids for an estimated molecular weight of 39513 Da.
Receptor for CCL19 and chemerin/RARRES2. Does not appear to be a signaling receptor, but may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a functional signaling receptors. Plays a critical role for the development of Th2 responses. (updated: Jan. 7, 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.
- 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, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs11574443 | |
| dbSNP:rs3204849 | |
| dbSNP:rs6441977 | |
| dbSNP:rs3204850 |
Biological Process
Calcium-mediated signaling
Cell chemotaxis
Chemokine-mediated signaling pathway
Chemotaxis
G protein-coupled receptor signaling pathway
Immune response
Inflammatory response
Positive regulation of cytosolic calcium ion concentration
The reference OMIM entry for this protein is 608379
Chemokine, cc motif, receptor-like protein 2; ccrl2
Hcr
Cram
DESCRIPTION
CCRL2 is an atypical chemokine receptor that may have a role in modulating chemokine-triggered immune responses (Hartmann et al., 2008).CLONING
By searching an EST database for significant homology to chemokine receptors, followed by library screening, Fan et al. (1998) obtained a genomic clone of CCRL2, which they designated HCR. The deduced 345-amino acid protein has a calculated molecular mass of 39.5 kD. CCRL2 contains a 7-transmembrane topography and 2 potential N-glycosylation sites. It shares 43.1% amino acid identity with CKR1 (601159) and 40.5 to 42.7% identity with several other cytokine receptors. Northern blot analysis detected a 1.7-kb transcript expressed predominantly in spleen, fetal liver, lymph node, bone marrow, lung, and heart. Expression was lower in thymus and placenta, marginal in skeletal muscle, and was not detected in several other tissues. Hartmann et al. (2008) noted that 2 CCLR2 splice variants exist, one encoding a 345-amino acid protein referred to as CCRL2B, CRAMB, CKRX, or HCR, and the other encoding a 357-amino acid protein referred to as CCRL2A or CRAMA.GENE FUNCTION
Using RT-PCR and flow cytometry, Hartmann et al. (2008) showed that CCL5 (187011) induced ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948) phosphorylation and expression of CRAMA and CRAMB, but not other CCL5-binding molecules, in a pre-B cell line. CCL5 did not induce calcium mobilization or migratory responses in the cell lines. Hartmann et al. (2008) suggested that CCRL2 may be involved in immunomodulatory functions together with CCL5. Zabel et al. (2008) identified chemerin (RARRES2; 601973) as a protein that interacted with, but was not internalized by, mouse and human CCRL2. They proposed that CCRL2 focuses chemerin localization and thereby contributes to inflammatory processes mediated by the chemerin receptor, CMKLR1 (602351). By screening for proteins that could bind human CCRL2, Leick et al. (2009) identified the homeostatic chemokine CCL19 (602227) as a CCRL2 ligand. CCL19 bound to CCRL2-expressing cells with an affinity comparable to its binding of CCR7 (600242), but binding to CCRL2 did not result in cellular activation for calcium mobilization or migration. Confocal microscopy showed that CCRL2 was constitutively recycled via clathrin-coated pits and could internalize CCL19, as well as anti-CCRL2 antibodies. Leick et al. (2009) concluded that CCRL2 is a nonclassical chemokine receptor that may be involved in modulating CCL19-mediated lymphocyte and dendritic cell trafficking.ANIMAL MODEL
Zabel et al. (2008) found that Ccrl2-knockout mice displayed no overt phenotype and had normal numbers of mast cells in all tissues analyzed. Analysis of Ccrl2-knockout mice showed that Ccrl2 was not required for expression of IgE-mediated mast cell-dependent passive cutaneous anaphylaxis. However, Ccrl2 was required for development of optimal cutaneous tissue swelling and leukocyte infiltrates after sensitization with low doses of antigen-specific IgE.MAPPING
By FISH, Fan et al. (1998) mapped the CCRL2 gene to chromosome X. However, Hartz (2004) mapped the CCRL2 gene to chromosome 3p21 based on an alignment of the CCRL2 sequence (GenBank GENBANK U97123) with the genomic sequence. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: comparative model for a membrane protein was added.
May 12, 2019: Protein entry updated
Automatic update: model status changed
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 608379 was added.