Complement component 9

Last updated

C9
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases C9 , ARMD15, C9D, complement component 9, complement C9
External IDs OMIM: 120940; MGI: 1098282; HomoloGene: 74406; GeneCards: C9; OMA:C9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

735

12279

Ensembl

ENSG00000113600

ENSMUSG00000022149

UniProt

P02748

P06683

RefSeq (mRNA)

NM_001737

NM_013485
NM_001368420
NM_001368421

RefSeq (protein)

NP_001728

NP_038513
NP_001355349
NP_001355350

Location (UCSC) Chr 5: 39.28 – 39.37 Mb Chr 15: 6.47 – 6.53 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Complement component 9 (C9) is a MACPF protein involved in the complement system, which is part of the innate immune system. [5] Once activated, about 12-18 molecules of C9 polymerize to form pores in target cell membranes, causing lysis and cell death. [6] C9 is one member of the complement membrane attack complex (MAC), which also includes complement components C5b, C6, C7 and C8. [7] [8] [9]   The formation of the MAC occurs through three distinct pathways: the classical, alternative, and lectin pathways. [7] Pore formation by C9 is an important way that bacterial cells are killed during an infection, and the target cell is often covered in multiple MACs. The clinical impact of a deficiency in C9 is an infection with the gram-negative bacterium Neisseria meningitidis. [10]

Contents

Structure

C9 genes include 11 exons and 10 introns when found in fish. [11] In fish, the liver is the site where the majority of complement components are produced and expressed, but C9 can also be found in other tissues. [11] It is a single-chain glycoprotein with a four domain structure arranged in a globular bundle. [10] [11]

Pore formation

MAC formation starts with the assembly of a tetrameric complex with the complement components C6, C7, C8, and C5b. [12] The final step of MAC on target cell surfaces involves the polymerization of C9 molecules bound to C5b8 forming C5b-9. [8] [10] [11] C9 molecules allow cylindrical, asymmetrical transmembrane pores to form. The overall complex belongs to MAC/perforin-like (MACPF)/CDC superfamily. [6] Pore formation involves binding the C9 molecules to the target membrane, membrane molecules forming a pre-pore shape, and conformational change in the TMH1, the first transmembrane region, and TMH2, the second transmembrane region. [8] The formations of pores leads to the killing of foreign pathogens and infected host cells.

Relation to aging process

C9 was found to be the most strongly under expressed serum protein in men who achieved longevity, compared to men who did not. [13]

Related Research Articles

<span class="mw-page-title-main">Complement system</span> Part of the immune system that enhances the ability of antibodies and phagocytic cells

The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. Despite being part of the innate immune system, the complement system can be recruited and brought into action by antibodies generated by the adaptive immune system.

<span class="mw-page-title-main">Perforin-1</span> Mammalian protein found in Homo sapiens

Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs).

<span class="mw-page-title-main">Classical complement pathway</span> Aspect of the immune system

The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM.

<span class="mw-page-title-main">Alternative complement pathway</span> Type of cascade reaction of the complement system

The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections.

<span class="mw-page-title-main">Complement membrane attack complex</span> Protein complex

The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells. Assembly of the MAC leads to pores that disrupt the cell membrane of target cells, leading to cell lysis and death.

<span class="mw-page-title-main">C5-convertase</span> Serine protease that plays key role in innate immunity.

C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity. It participates in the complement system ending with cell death.

<span class="mw-page-title-main">Complement component 5a</span> Protein fragment

C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b fragments. C5b is important in late events of the complement cascade, an orderly series of reactions which coordinates several basic defense mechanisms, including formation of the membrane attack complex (MAC), one of the most basic weapons of the innate immune system, formed as an automatic response to intrusions from foreign particles and microbial invaders. It essentially pokes microscopic pinholes in these foreign objects, causing loss of water and sometimes death. C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of the MAC, attraction of innate immune cells, and histamine release involved in allergic responses. The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of C5a. C5a is a chemotactic agent and an anaphylatoxin; it is essential in the innate immunity but it is also linked with the adaptive immunity. The increased production of C5a is connected with a number of inflammatory diseases.

<span class="mw-page-title-main">Integrin alpha X</span> Mammalian protein found in Homo sapiens

CD11c, also known as Integrin, alpha X (ITGAX), is a gene that encodes for CD11c.

<span class="mw-page-title-main">Complement component 5</span> Protein found in humans

Complement component 5 is a protein that in humans is encoded by the C5 gene.

<span class="mw-page-title-main">Pore-forming toxin</span> Protein-produced toxins that create pores in cell membrane

Pore-forming proteins are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthworms, who produce lysenin. They are frequently cytotoxic, as they create unregulated pores in the membrane of targeted cells.

<span class="mw-page-title-main">Hemolysin</span> Molecule destroying the membrane of red blood cells

Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acquisition, many hemolysins produced by pathogens do not cause significant destruction of red blood cells during infection. However, hemolysins are often capable of lysing red blood cells in vitro.

<span class="mw-page-title-main">C3b</span>

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.

<span class="mw-page-title-main">CD59</span> Mammalian protein found in humans

CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the CD59 gene. It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxin protein family.

<span class="mw-page-title-main">CD9</span> Human protein-encoding gene

CD9 is a gene encoding a protein that is a member of the transmembrane 4 superfamily also known as the tetraspanin family. It is a cell surface glycoprotein that consists of four transmembrane regions and has two extracellular loops that contain disulfide bonds which are conserved throughout the tetraspanin family. Also containing distinct palmitoylation sites that allows CD9 to interact with lipids and other proteins.

The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system and perforin (PF). Members of this protein family are pore-forming toxins (PFTs). In eukaryotes, MACPF proteins play a role in immunity and development.

<span class="mw-page-title-main">CD97</span> Mammalian protein found in humans

Cluster of differentiation 97 is a protein also known as BL-Ac[F2] encoded by the ADGRE5 gene. CD97 is a member of the adhesion G protein-coupled receptor (GPCR) family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

<span class="mw-page-title-main">SLAMF1</span> Protein-coding gene in humans

Signaling lymphocytic activation molecule 1 is a protein that in humans is encoded by the SLAMF1 gene. Recently SLAMF1 has also been designated CD150.

<span class="mw-page-title-main">CD276</span> Protein found in humans

Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.

<span class="mw-page-title-main">Tetherin</span> Mammalian protein found in Homo sapiens

Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene. In addition, tetherin has been designated as CD317. This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.

<span class="mw-page-title-main">PIEZO1</span> Protein-coding gene in the species Homo sapiens

Piezo-type mechanosensitive ion channel component 1 is a protein that in humans is encoded by the PIEZO1 gene. PIEZO1 is a large mechanosensitive ion channel protein that forms a homotrimeric complex with a distinctive three-bladed, propeller-shaped architecture. Each subunit of PIEZO1 contains between 30 and 40 transmembrane domains. The protein consists of a central pore module and peripheral mechanotransduction modules. The pore module is composed of the last two transmembrane helices, an extracellular cap domain, and an intracellular C-terminal domain.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000113600 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022149 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Lint TF, Zeitz HJ, Gewurz H (November 1980). "Inherited deficiency of the ninth component of complement in man". Journal of Immunology. 125 (5): 2252–7. doi: 10.4049/jimmunol.125.5.2252 . PMID   7430628.
  6. 1 2 Dudkina NV, Spicer BA, Reboul CF, Conroy PJ, Lukoyanova N, Elmlund H, et al. (February 2016). "Structure of the poly-C9 component of the complement membrane attack complex". Nature Communications. 7 (1): 10588. Bibcode:2016NatCo...710588D. doi:10.1038/ncomms10588. PMC   4742998 . PMID   26841934.
  7. 1 2 Mohapatra A, Das S, Dey S, Sahoo PK (April 2020). "Molecular characterization and induced expression analysis of the terminal complement component C9 in rohu, Labeo rohita". Aquaculture Research. 51 (4): 1415–1427. doi: 10.1111/are.14487 . ISSN   1355-557X. S2CID   213565293.
  8. 1 2 3 Spicer BA, Law RH, Caradoc-Davies TT, Ekkel SM, Bayly-Jones C, Pang SS, et al. (August 2018). "The first transmembrane region of complement component-9 acts as a brake on its self-assembly". Nature Communications. 9 (1): 3266. Bibcode:2018NatCo...9.3266S. doi:10.1038/s41467-018-05717-0. PMC   6093860 . PMID   30111885.
  9. ↑ Wickramaarachchi WD, Wan Q, Lee Y, Lim BS, De Zoysa M, Oh MJ, et al. (October 2012). "Genomic characterization and expression analysis of complement component 9 in rock bream (Oplegnathus fasciatus)". Fish & Shellfish Immunology. 33 (4): 707–17. doi:10.1016/j.fsi.2012.06.019. PMID   22796422.
  10. 1 2 3 Fu X, Ju J, Lin Z, Xiao W, Li X, Zhuang B, et al. (July 2016). "Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)-induced acute shock in mice". Scientific Reports. 6 (1): 30239. Bibcode:2016NatSR...630239F. doi:10.1038/srep30239. PMC   4957234 . PMID   27444648.
  11. 1 2 3 4 Li L, Chang MX, Nie P (August 2007). "Molecular cloning, promoter analysis and induced expression of the complement component C9 gene in the grass carp Ctenopharyngodon idella". Veterinary Immunology and Immunopathology. 118 (3–4): 270–82. doi:10.1016/j.vetimm.2007.05.005. PMID   17604124.
  12. ↑ Fu YW, Zhu CK, Zhang QZ (May 2019). "Molecular characterization and expression analysis of complement components C3 and C9 in largemouth bronze gudgeon (Coreius guichenoti) in response to Ichthyophthirius multifiliis infection". Aquaculture. 506: 270–279. Bibcode:2019Aquac.506..270F. doi:10.1016/j.aquaculture.2019.03.046. S2CID   133378035.
  13. ↑ Orwoll E, Wiedrick J, Nielson C, et al. (2020). "Proteomic assessment of serum biomarkers of longevity in older men". Aging Cell. 19 (11): e13253. doi: 10.1111/acel.13253 . PMC   7681066 . PMID   33078901.
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