Complement C1r subcomponent-like protein (C1RL)
The protein contains 487 amino acids for an estimated molecular weight of 53498 Da.
Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
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:rs3742089 |
No binding partner found
Biological Process
Complement activation, classical pathway
Innate immune response
Zymogen activation
The reference OMIM entry for this protein is 608974
Complement component c1r-like protein; c1rl
C1r-like serine protease analog; clspa
C1r-like protein; c1rlp
CLONING
By large-scale random sequencing of a dendritic cell cDNA library, Lin et al. (2004) cloned C1RL, which they called CLSPA. The deduced 487-amino acid protein has a calculated molecular mass of about 53.5 kD. It has an N-terminal signal peptide, a conserved CUB domain, a truncated complement control protein module, and a trypsin-like serine protease domain. It also has 2 N-glycosylation sites and 3 conserved cysteines in the CUB domain, but it lacks a consensus sequence for activation by upstream trypsin-like proteases. C1RL shares sequence similarity with C1r (613785), C1s (120580), and MASPs (see 600521). PCR analysis detected C1RL expression in all tissues examined except brain. Highest expression was in placenta, liver, kidney, and pancreas. C1RL was secreted by transfected HEK293 cells.GENE FUNCTION
Lin et al. (2004) found C1RL mRNA upregulated in monocytic cells and monocyte-derived immature dendritic cells by agonistic anti-CD40 (109535) antibody, TNFA (191160), and lipopolysaccharide. Supernatant collected from C1RL-transfected HEK293 cells reduced complement-mediated cytotoxicity in antibody-sensitized erythrocytes. C1RL transfection also reduced the endogenous proteolytic activity in the lysates of transfected HEK293 cells. Haptoglobin (HP; 140100) is an unusual secretory protein in that it is proteolytically processed in the endoplasmic reticulum and not in the Golgi. Wicher and Fries (2004) found that C1RL mediates this cleavage. Coexpression of the proform of HP (proHP) and C1RL in COS-1 cells resulted in the cleavage of proHP in the endoplasmic reticulum. C1RL showed specificity for proHP, in that it did not cleave the proform of complement C1s, a protein similar to HP, particularly around the cleavage site. Suppression of C1RL expression by RNA interference reduced the cleavage of proHP by up to 45%.GENE STRUCTURE
Lin et al. (2004) determined that the C1RL gene contains 6 exons.MAPPING
By genomic sequence analysis, Lin et al. (2004) mapped the C1RL gene to chromosome 12p13.31. ... More on the omim web site
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 608974 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).