C9
entrez
735
canonical
uniprot
P02748
canonical
ensembl
ENSG00000113600
resolver
ensp
ENSP00000263408
resolver
ensp
ENSP00000554698
resolver
enst
ENST00000263408
resolver
enst
ENST00000884639
resolver
genesymbol
C9
resolver
hgnc
HGNC:1358
resolver
uniprot_entry
CO9_HUMAN
resolver
activity_regulation
ACTIVITY REGULATION: Membrane attack complex (MAC) assembly is inhibited by CD59, thereby protecting self-cells from damage during complement activation (PubMed:36797260). CD59 acts by preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (PubMed:36797260). MAC assembly is also inhibited by clusterin (CLU) chaperones that inhibit polymerization of C9 (PubMed:34667172). Specifically inhibited by the antibody aE11, thereby inhibiting MAC assembly (PubMed:36639734). {ECO:0000269|PubMed:34667172, ECO:0000269|PubMed:36639734, ECO:0000269|PubMed:36797260}.
uniprot
proteins
amino_acid_sequence
MSACRSFAVAICILEISILTAQYTTSYDPELTESSGSASHIDCRMSPWSEWSQCDPCLRQMFRSRSIEVFGQFNGKRCTDAVGDRRQCVPTEPCEDAEDDCGNDFQCSTGRCIKMRLRCNGDNDCGDFSDEDDCESEPRPPCRDRVVEESELARTAGYGINILGMDPLSTPFDNEFYNGLCNRDRDGNTLTYYRRPWNVASLIYETKGEKNFRTEHYEEQIEAFKSIIQEKTSNFNAAISLKFTPTETNKAEQCCEETASSISLHGKGSFRFSYSKNETYQLFLSYSSKKEKMFLHVKGEIHLGRFVMRNRDVVLTTTFVDDIKALPTTYEKGEYFAFLETYGTHYSSSGSLGGLYELIYVLDKASMKRKGVELKDIKRCLGYHLDVSLAFSEISVGAEFNKDDCVKRGEGRAVNITSENLIDDVVSLIRGGTRKYAFELKEKLLRGTVIDVTDFVNWASSINDAPVLISQKLSPIYNLVPVKMKNAHLKKQNLERAIEDYINEFSVRKCHTCQNGGTVILMDGKCLCACPFKFEGIACEISKQKISEGLPALEFPNEK
uniprot
proteins
disease_involvement
DISEASE: Complement component 9 deficiency (C9D) [MIM:613825]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may develop dermatomyositis. {ECO:0000269|PubMed:9634479}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 15 (ARMD15) [MIM:615591]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:24036952}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Pore-forming component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22832194, PubMed:26841837, PubMed:26841934, PubMed:27052168, PubMed:30552328, PubMed:6177822, PubMed:9212048, PubMed:9634479). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:39914456, PubMed:39814882, PubMed:9212048, PubMed:9634479). The complement pathways consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:9212048, PubMed:9634479). Constitutes the pore-forming subunit of the MAC complex: during MAC assembly, C9 associates with the C5b8 intermediate complex, and polymerizes to complete the pore (PubMed:26841934, PubMed:30111885, PubMed:30552328, PubMed:34752492, PubMed:4055801, PubMed:6177822). {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841837, ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:27052168, ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:30552328, ECO:0000269|PubMed:34752492, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:6177822, ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}.
uniprot
proteins
mass_dalton
63173
uniprot
proteins
mutagenesis
MUTAGEN 86..93; /note="RQCVPTEP->QQCEPTEE: Abolished inhibition by the antibody aE11."; /evidence="ECO:0000269|PubMed:36639734"; MUTAGEN 86; /note="R->Q: Slightly reduced inhibition by the antibody aE11."; /evidence="ECO:0000269|PubMed:36639734"; MUTAGEN 89; /note="V->E: Reduced inhibition by the antibody aE11."; /evidence="ECO:0000269|PubMed:36639734"; MUTAGEN 93; /note="P->E: Does not affect inhibition by the antibody aE11."; /evidence="ECO:0000269|PubMed:36639734"; MUTAGEN 283; /note="F->C: Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-427."; /evidence="ECO:0000269|PubMed:30111885"; MUTAGEN 426; /note="V->C: Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-283."; /evidence="ECO:0000269|PubMed:30111885
uniprot
proteins
post_translational_modification
PTM: Thrombin cleaves factor C9 to produce C9a and C9b. {ECO:0000269|PubMed:4055801}.; PTM: Phosphorylation sites are present in the extracellular medium. {ECO:0000269|PubMed:10408378}.; PTM: Initially, positions and connectivity of disulfide bonds were based on peptide sequencing done for the human protein (PubMed:8603752). The crystal structures for the human and mouse proteins corrected the positions and connectivities of the disulfide bonds (PubMed:30111885). The distance between Cys-57 and Cys-94 in the monomeric mouse protein precludes formation of a disulfide bond, contrary to what is seen in the structure of the human polymeric form of the protein (Probable). {ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:8603752, ECO:0000305|PubMed:30111885}.
uniprot
proteins
protein_family
Complement C6/C7/C8/C9 family
uniprot
proteins
pubmed
10408378
uniprot
proteins
pubmed
10551839
uniprot
proteins
pubmed
14760718
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
22832194
uniprot
proteins
pubmed
2395434
uniprot
proteins
pubmed
24036952
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26841837
uniprot
proteins
pubmed
26841934
uniprot
proteins
pubmed
27052168
uniprot
proteins
pubmed
30111885
uniprot
proteins
pubmed
30552328
uniprot
proteins
pubmed
31061395
uniprot
proteins
pubmed
3219351
uniprot
proteins
pubmed
34667172
uniprot
proteins
pubmed
34752492
uniprot
proteins
pubmed
36639734
uniprot
proteins
pubmed
36797260
uniprot
proteins
pubmed
39814882
uniprot
proteins
pubmed
39914456
uniprot
proteins
pubmed
4018030
uniprot
proteins
pubmed
4055801
uniprot
proteins
pubmed
6095282
uniprot
proteins
pubmed
6177822
uniprot
proteins
pubmed
8603752
uniprot
proteins
pubmed
9212048
uniprot
proteins
pubmed
9634479
uniprot
proteins
sequence_length
559
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:8603752, ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}. Target cell membrane {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:30552328, ECO:0000269|PubMed:31061395, ECO:0000269|PubMed:34752492, ECO:0000269|PubMed:9212048}; Multi-pass membrane protein {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30552328}. Note=Secreted as soluble monomer (PubMed:26841934, PubMed:30111885, PubMed:4055801, PubMed:9634479). Oligomerizes at target membranes, forming a pre-pore (PubMed:26841934, PubMed:30111885, PubMed:31061395, PubMed:4055801, PubMed:9634479). A conformation change then leads to the formation of a 100 Angstrom diameter pore (PubMed:26841934, PubMed:30111885, PubMed:31061395, PubMed:4055801, PubMed:9634479). {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:31061395, ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9634479}.
uniprot
proteins
transmembrane_region
TRANSMEM 235..242; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H03, ECO:0007744|PDB:6H04"; TRANSMEM 265..272; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H03, ECO:0007744|PDB:6H04"; TRANSMEM 374..381; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H03, ECO:0007744|PDB:6H04"; TRANSMEM 382..390; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H03, ECO:0007744|PDB:6H04
uniprot
proteins