CD46

Protein identityUniProt · HPA

UniProt accession

P15529

Gene

CD46

Ensembl

ENSG00000117335

Chromosome

1

Canonical length

392 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

OverviewNCBI Gene

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 of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

392 residues, UniProt reviewed canonical sequence.

>P15529|CD46
     1  MEPPGRRECP FPSWRFPGLL LAAMVLLLYS FSDACEEPPT FEAMELIGKP KPYYEIGERV
    61  DYKCKKGYFY IPPLATHTIC DRNHTWLPVS DDACYRETCP YIRDPLNGQA VPANGTYEFG
   121  YQMHFICNEG YYLIGEEILY CELKGSVAIW SGKPPICEKV LCTPPPKIKN GKHTFSEVEV
   181  FEYLDAVTYS CDPAPGPDPF SLIGESTIYC GDNSVWSRAA PECKVVKCRF PVVENGKQIS
   241  GFGKKFYYKA TVMFECDKGF YLDGSDTIVC DSNSTWDPPV PKCLKVLPPS STKPPALSHS
   301  VSTSSTTKSP ASSASGPRPT YKPPVSNYPG YPKPEEGILD SLDVWVIAVI VIAIVVGVAV
   361  ICVVPYRYLQ RRKKKGTYLT DETHREVKFT SL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD46 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

286 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD46.

Disease | AllUniProt

Conditions CD46 is implicated in, by any mechanism.

• Hemolytic uremic syndrome, atypical, 2 (AHUS2) MIM:612922

Disease | GeneticClinVar

73 pathogenic / likely-pathogenic of 593 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Atypical hemolytic-uremic syndrome
• Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly
• Familial Atypical Hemolytic-Uremic Syndrome
• Nonpapillary renal cell carcinoma
• Autosomal dominant and autosomal recessive CD46-related disorders

Disease | ImmuneIEDB

Conditions an epitope on CD46 was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

ReferencesPubMed · IEDB

Publications for CD46 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.9

gnomAD pLI

0

gnomAD missense Z

0.62

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• complement activation, classical pathway
• innate immune response
• negative regulation of complement activation, classical pathway
• negative regulation of gene expression
• positive regulation of gene expression
• positive regulation of interleukin-10 production
• positive regulation of memory T cell differentiation
• positive regulation of regulatory T cell differentiation
• positive regulation of T cell proliferation
• positive regulation of transforming growth factor beta production
• regulation of Notch signaling pathway
• single fertilization
• T cell mediated immunity
• sequestering of extracellular ligand from receptor

Molecular functions

• cadherin binding
• signaling receptor activity
• virus receptor activity

Cellular components

• cell surface
• extracellular exosome
• extracellular space
• focal adhesion
• inner acrosomal membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Sushi/SCR/CCP superfamily
• SEZ6/CSMD/C4BPB Neuronal & Immune Regulators
• Sushi repeat (SCR repeat)
• Membrane cofactor protein CD46

KeywordsUniProt

• Complement pathway
• Cytoplasmic vesicle
• Disulfide bond
• Fertilization
• Glycoprotein
• Hemolytic uremic syndrome
• Host cell receptor for virus entry
• Host-virus interaction
• Immunity
• Innate immunity
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Sushi
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CD46 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MSN