CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the CD46 gene. [5] CD46 is an inhibitory complement receptor. [6]
CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the CD46 gene. [5] CD46 is an inhibitory complement receptor. [6]
This gene is found in a cluster on chromosome 1q32 with other genes encoding structural components of the complement system. At least fourteen different transcript variants encoding fourteen different isoforms have been found for this gene. [7]
The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system.
The encoded protein has cofactor activity for inactivation (through cleavage) of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. [8]
The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. [9]
The encoded protein can act as a receptor for the Edmonston strain of measles virus, [10] human herpesvirus-6 (HHV-6), group B adenoviruses, [11] and type IV pili of pathogenic Neisseria . [12]
The extracellular region of CD46 contains four short consensus repeats (SCR) of about 60 amino acids that fold into a compact beta-barrel domain surrounded by flexible loops. [13] As has been demonstrated for CD46 with other ligands, the CD46 protein structure is believed to linearize upon binding HHV-6. While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated to be required for HHV-6 receptor binding and cellular entry. The heterotetramer gH/gL/gQ1/gQ2 complex of HHV-6 has been identified as a CD46 ligand. [14]
Established medulloblastoma (a malignant brain tumor common in childhood) specimens express CD46, and that medulloblastoma specimens removed from patients had a high level of CD46 expression. Therefore, a vaccine made of the Edmonston strain of measles virus could treat the medulloblastoma. Such a vaccine has already been tested in a number of trials involving other tumor types which have a high expression of CD46, including one type of adult brain tumor. [15]
Recently, CD46 has emerged as a promising target for the treatment of both adenocarcinoma and neuroendocrine types of metastatic castration-resistant prostate cancer (mCRPC). [16] [17] YS5, a human full-length IgG1 with high specificity for CD46, was identified to have high binding affinity for prostate cancer tissue. [16] YS5 has been developed into an antibody-drug conjugate, FOR46, which is currently in a phase I clinical trial (NCT03575819) for the treatment of mCRPC. Since then, a companion molecular imaging agent for CD46-targeted therapy has been developed. [18]
CD46 deficiency contributes to inflammation disorders. [19]
CD46 has been shown to interact with CD9, [20] CD151 [20] and CD29. [20]
Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 is a protein that in humans is encoded by the CR1 gene.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses. Even after many years since the discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.
Human herpesvirus 6 (HHV-6) is the common collective name for human betaherpesvirus 6A (HHV-6A) and human betaherpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host.
HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus (HHV) infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA. LAT regulates the viral genome and interferes with the normal activities of the infected host cell.
Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.
Complement component 5 is a protein that in humans is encoded by the C5 gene.
Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.
Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21, is a protein that in humans is encoded by the CR2 gene.
Chemokine ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.
Complement control protein are proteins that interact with components of the complement system.
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.
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.
Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release. It is a member of the tumor necrosis factor receptor superfamily.
Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.
Poliovirus receptor-related 2 (PVRL2), also known as nectin-2 and CD112, is a human plasma membrane glycoprotein.
Chemokine-binding protein 2 is a protein that in humans is encoded by the CCBP2 gene.
Poliovirus receptor-related 1 (PVRL1), also known as nectin-1 and CD111 (formerly herpesvirus entry mediator C, HVEC) is a human protein of the immunoglobulin superfamily (IgSF), also considered a member of the nectins. It is a membrane protein with three extracellular immunoglobulin domains, a single transmembrane helix and a cytoplasmic tail. The protein can mediate Ca2+-independent cellular adhesion further characterizing it as IgSF cell adhesion molecule (IgSF CAM).
OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.
Eukaryotic translation initiation factor 3, subunit M (eIF3m) also known as PCI domain containing 1 (herpesvirus entry mediator) (PCID1), is a protein that in humans is encoded by the EIF3M gene.
Measles virus encoding the human thyroidal sodium iodide symporter or MV-NIS is an attenuated oncolytic Edmonston (Ed) strain of measles virus.