UniProt functional annotation for P02748



	UniProt functional annotation for P02748

UniProt code: P02748.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}.

Subunit: Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9 (PubMed:22832194). About 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes (PubMed:26841934, PubMed:30111885). {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885}.

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:9212048}; Multi-pass membrane protein {ECO:0000269|PubMed:26841934}. Note=Secreted as soluble monomer. Oligomerizes at target membranes, forming a pre-pore. A conformation change then leads to the formation of a 100 Angstrom diameter pore. {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885, ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9634479}.

Tissue specificity: Plasma (at protein level). {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:8603752, ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}.

Ptm: Thrombin cleaves factor C9 to produce C9a and C9b. {ECO:0000269|PubMed:4055801}.

Ptm: Phosphorylation sites are present in the extracellular medium.

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}.

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.

Similarity: Belongs to the complement C6/C7/C8/C9 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000269\|PubMed:26841934, ECO:0000269\|PubMed:30111885, ECO:0000269\|PubMed:4055801, ECO:0000269\|PubMed:9212048, ECO:0000269\|PubMed:9634479}.


Subunit:		Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9 (PubMed:22832194). About 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes (PubMed:26841934, PubMed:30111885). {ECO:0000269\|PubMed:22832194, ECO:0000269\|PubMed:26841934, ECO:0000269\|PubMed:30111885}.
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:9212048}; Multi-pass membrane protein {ECO:0000269\|PubMed:26841934}. Note=Secreted as soluble monomer. Oligomerizes at target membranes, forming a pre-pore. A conformation change then leads to the formation of a 100 Angstrom diameter pore. {ECO:0000269\|PubMed:26841934, ECO:0000269\|PubMed:30111885, ECO:0000269\|PubMed:4055801, ECO:0000269\|PubMed:9634479}.
Tissue specificity:		Plasma (at protein level). {ECO:0000269\|PubMed:22832194, ECO:0000269\|PubMed:26841934, ECO:0000269\|PubMed:8603752, ECO:0000269\|PubMed:9212048, ECO:0000269\|PubMed:9634479}.
Ptm:		Thrombin cleaves factor C9 to produce C9a and C9b. {ECO:0000269\|PubMed:4055801}.
Ptm:		Phosphorylation sites are present in the extracellular medium.
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}.
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.
Similarity:		Belongs to the complement C6/C7/C8/C9 family. {ECO:0000305}.