Complement factor H-related protein 1 (CFHR1)
The protein contains 330 amino acids for an estimated molecular weight of 37651 Da.
Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with lipoproteins and may play a role in lipid metabolism. (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:rs425757 | |
| dbSNP:rs410232 | |
| dbSNP:rs388862 | |
| dbSNP:rs16840561 |
Biological Process
Complement activation
Cytolysis by host of symbiont cells
Negative regulation of protein binding
Positive regulation of cytolysis
Regulation of complement activation
Cellular Component
Blood microparticle
Extracellular region
Extracellular space
Protein-containing complex
The reference OMIM entry for this protein is 134371
Complement factor h-related 1; cfhr1
Factor h-related gene 1; fhr1
H factor-like 1; hfl1
CLONING
Timmann et al. (1991) isolated 2 differently glycosylated forms of a human serum protein antigenically related to complement factor H (CFH; 134370). Skerka et al. (1991) isolated a cDNA clone for this protein that predicted a protein sequence of 327 amino acids with a leader sequence. The secreted part of the protein comprised 5 tandem repeating units, termed short consensus repeats (SCRs). The 3-prime end showed sequence homology to the 3-prime end of human complement factor H. Skerka et al. (1991) also isolated a cDNA clone that appeared to represent a transcribed pseudogene, since it contained a stop codon (TAA) within SCR 1. See also Zipfel and Skerka (1994).MAPPING
Gross (2014) mapped the CFHR1 gene to chromosome 1q31.3 based on an alignment of the CFHR1 sequence (GenBank GENBANK BC107771) with the genomic sequence (GRCh37).GENE FUNCTION
By immunoprecipitation and immunoblot analyses, Kunert et al. (2007) found that factor H, via SCR domains 6 to 7 and 19 to 20, and FHR1, via SCR domains 3 to 5, bound to surface-expressed Pseudomonas aeruginosa elongation factor Tuf and also to recombinant Tuf. Factor H and plasminogen (PLG; 173350) bound simultaneously to Tuf, and PLG was proteolytically activated. Plasma without factor H did not support P. aeruginosa survival, and survival increased in a factor H dose-dependent manner. Kunert et al. (2007) proposed that Tuf acts as a virulence factor by acquiring host proteins to the pathogen surface, controlling complement, and possibly facilitating tissue invasion.MOLECULAR GENETICS
Feifel et al. (1992) and Meyer et al. (1995) described polymorphisms of the factor H-related gene. Hughes et al. (2006) found that a haplotype carrying an 84-kb deletion of the CFHR1 and CFHR3 (605336) genes (134371.0001) was associated with a decreased risk of age-related macular degeneration (see ARMD1, 603075). The authors did not assess the relative importance of the deletion of CFHR1 and CFHR3 in contributing to the protective nature of the haplotype; however, they noted that the products of both genes are present in the circulation, where they have the potential to compete with CFH for C3 (120700) binding. Hughes et al. (2006) hypothesized that CFH produced from full-length transcript is beneficial and that other CFH-related proteins interfere with regulation of complement activity. Extending their previous work (see Hughes et al., 2006), Zipfel et al. (2007) found that the 84-kb CFHR1/CFHR3 deletion was associated with an increased risk of atypical hemolytic-uremic syndrome (aHUS; 235400) in 2 independent European cohorts. Zipfel et al. (2007) noted that the present study showed an opposite effect for the variant from that of Hughes et al. (2006), which may be due to a disease-modifying action of the deletion or linkage disequilibrium between the deletion and other susceptibility alleles. Of 147 patients with aHUS, 121 of whom had previously been reported by Zipfel et al. (2007), Jozsi et al. (2008) identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. In 711 individuals with ARMD and 1,041 controls, Raychaudhuri et al. (2010) reproduced associations at the Y402H allele (134370.0008), using dbSNP rs10801555 as a proxy, and dbSNP rs1410996 (134370.0016), using dbSNP rs1073 ... More on the omim web site
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 134371 was added.