Complement component C9 (C9)
The protein contains 559 amino acids for an estimated molecular weight of 63173 Da.
Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells (PubMed:9634479, PubMed:9212048, PubMed:26841934). C9 is the pore-forming subunit of the MAC (PubMed:4055801, PubMed:26841934, PubMed:30111885). (updated: Jan. 16, 2019)
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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs700233 | |
| C9D | |
| dbSNP:rs696763 | |
| ARMD15 | |
| dbSNP:rs13361416 | |
| dbSNP:rs34625111 | |
| dbSNP:rs34421659 |
Biological Process
Cell killing
Complement activation
Complement activation, alternative pathway
Complement activation, classical pathway
Cytolysis
Hemolysis by symbiont of host erythrocytes
Innate immune response
Protein homooligomerization
Regulation of complement activation
Cellular Component
Blood microparticle
Cytoplasm
Cytosol
Extracellular exosome
Extracellular region
Extracellular space
Integral component of plasma membrane
Membrane attack complex
Other organism cell membrane
Plasma membrane
Molecular Function
The reference OMIM entry for this protein is 120940
Complement component 9; c9
DESCRIPTION
Activation of the complement system results in formation of the membrane attack complex (MAC) on the membranes of target cells. The complex is assembled by sequential addition of 1 molecule each of C5b (120900), C6 (217050), C7 (217070), and C8 (see 120950) and 6 to 16 molecules of the ninth component, C9. MAC assembly results in membrane disruption, leading to death of the target cell (summary by DiScipio et al., 1984).CLONING
DiScipio et al. (1984) screened a human liver cDNA library by the colony-hybridization technique using 2 radiolabelled oligonucleotide probes corresponding to regions of the C9 amino acid sequence. The cDNA coding for C9 was sequenced. The derived protein consists of 537 amino acids in a single polypeptide chain. The N-terminal half of C9 is predominantly hydrophilic, whereas the C-terminal half is more hydrophobic. The amphipathic organization of the primary structure is consistent with the potential of polymerized C9 to penetrate lipid bilayers and cause the formation of transmembrane channels as part of the lytic action of MAC. Marazziti et al. (1988) compared the protein structure of C9 with that of low density lipoprotein receptor (LDLR; 606945).GENE STRUCTURE
Marazziti et al. (1988) compared the gene structure of C9 with that of LDLR (606945). The C9 gene contains 11 exons with lengths of 100 to 250 bp, except for exon 11, which includes the 3-prime UTR and extends over more than 1 kb. Witzel-Schlomp et al. (1997) gave revised information on the structure of the C9 gene, especially the exon-intron boundaries.MAPPING
By hybridizing a cloned cDNA coding for human complement factor C9 to hybrid cells containing subsets of human chromosomes on a rodent background, Rogne et al. (1989) localized the gene for C9 to chromosome 5. Abbott et al. (1989) used a novel application of PCR to amplify specifically the human C9 gene on a background of rodent DNA in somatic cell hybrids. The assignment of the gene to 5p13 was confirmed and regionalized by in situ hybridization. Coto et al. (1991) identified RFLPs for the C6, C7, and C9 loci and showed that these 3 loci are tightly linked. When examining the haplotypes of unrelated parents in their family study, they found significant linkage disequilibrium between C6 and C7 and between C7 and C9. Thus, the so-called terminal complement components are encoded by a cluster of genes. Coto et al. (1991) suggested that this cluster be referred to as MACII, MACI being the C8A (120950) and C8B (120960) cluster. Rogne et al. (1991) used DNA polymorphism of C9 and protein variants of C6 to show that the 2 genes are closely linked (maximum lod = 9.28 at theta = 0.00). They found no indication of allelic association. Setien et al. (1993) found that although the C6 and C7 genes are contained in the same NotI fragment of 500 kb, no evidence of physical linkage between C9 and C6 or C7 could be found in a range 50 kb to 2.5 Mb.MOLECULAR GENETICS
- C9 Deficiency In members of a Swiss family with C9 deficiency (613825), originally reported by Zoppi et al. (1990), Witzel-Schlomp et al. (1997) identified compound heterozygous mutations in the C9 gene (C33X, 120940.0002 and R133X, 120940.0007). Horiuchi et al. (1998) reported the molecular basis for C9 deficiency in 10 unrelated Japanese individuals. By use of exon-specific PCR/single-strand conformation polymorphism analysis, they demonstrated aberrantly migrating DNA bands ... More on the omim web site
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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 25, 2017: Additional information
No protein expression data in P. Mayeux work for C9
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 120940 was added.