CD46

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CD46
Available structures
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_010778

RefSeq (protein)

NP_034908

Location (UCSC)Chr 1: 207.75 – 207.8 MbChr 1: 194.72 – 194.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Gene

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]

Function

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

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]

Clinical significance

Measles infection

The encoded protein can act as a receptor for the Edmonston strain of

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]

Medulloblastoma

Established

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]

Prostate cancer

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]

Inflammatory diseases

CD46 deficiency contributes to inflammation disorders.[19]

Interactions

CD46 has been shown to

CD29.[20]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000117335Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016493Ensembl, 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. PMID 7929741
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  7. ^ "Entrez Gene: CD46 CD46 molecule, complement regulatory protein".
  8. PMID 15324743
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External links

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