IgG receptor FcRn large subunit p51 (FCGRT)

The protein contains 365 amino acids for an estimated molecular weight of 39743 Da.

 

Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk (PubMed:7964511, PubMed:10933786). IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation (PubMed:10998088). In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin/ALB (PubMed:24469444, PubMed:28330995).', '(Microbial infection) Acts as an uncoating receptor for a panel of echoviruses including Echovirus 5, 6, 7, 9, 11, 13, 25 and 29. (updated: July 31, 2019)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 75%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 601437

Fc fragment of igg, receptor transporter, alpha; fcgrt
Immunoglobulin receptor, intestinal, heavy chain

CLONING

The intestinal epithelium of neonatal mice and rats expresses an Fc receptor (FcRn) that mediates the selective uptake of immunoglobulin G (IgG) in mothers' milk, thereby helping newborn animals to acquire passive immunity. Kandil et al. (1996) noted that the IgG in the milk is bound to FcRn at the apical surface of the intestinal epithelium, and the resultant FcRn-IgG complexes are transcytosed across the epithelium. At the basolateral surface of intestinal epithelial cells, IgG is released from FcRn into blood or tissue fluids. FcRn is structurally similar to the major histocompatibility complex class I molecule, which presents antigenic peptides to T cells. Like the MHC class I molecule, FcRn is made up of a heavy chain (approximately 48 kD) and beta-2-microglobulin (109700; approximately 12 kD). Its heavy chain shows approximately 35% amino acid sequence identity to that of a typical MHC class I molecule. Furthermore, the genomic organizations of the MHC class I and mouse FcRn heavy chain genes are similar in that the signal peptide, the 3 extracellular domains, the transmembrane region, and the cytoplasmic region are all encoded by separate exons. Story et al. (1994) cloned a cDNA encoding the human gene and symbolized it FcRn. Kandil et al. (1996) isolated human genomic clones for the gene (symbolized FCGRT by them) using 2 murine Fcgrt probes. The exonic sequences of the genomic clones are identical to the cDNA sequence described by Story et al. (1994).

GENE FUNCTION

Plasma protein catabolism occurs in vascular endothelium by endocytotic processing of plasma contents. Vascular endothelium is the most active endocytic tissue in the body and the principal site for plasma protein catabolism. Plasma proteins diffusing or transported into extravascular sites are isolated from catabolism while extravascular. The receptor encoded by the FCGRT gene, alternatively called the Brambell receptor, the protection receptor, or the neonatal receptor, is located in endosomes of vascular endothelial cells and selectively recycles IgG to the cell surface, thus protecting IgG from lysosomal catabolism that is the fate of other, nonprotected plasma proteins. In mice with knockout of this receptor, the fractional catabolic rate for IgG may be accelerated up to 10-fold relative to wildtype animals in which protection is intact (Junghans and Anderson, 1996). This protection mechanism is directly responsible for making IgG the longest lived of all plasma proteins (Waldmann and Strober, 1969). Junghans et al. (2001) postulated that long-range cis inactivation of the FCGRT gene is responsible for hypercatabolism of IgG in myotonic dystrophy (DM; 160900). The FCGRT gene is closely situated to the DMPK gene (605377), which is mutant in DM.

MAPPING

Ahouse et al. (1993) found that the mouse FcRn heavy chain gene, designated Fcgrt, maps to chromosome 7 and thus is not encoded by the MHC. Kandil et al. (1996) showed by fluorescence in situ hybridization that the human gene, FCGRT, maps to 19q13.3. Thus, like its mouse counterpart, FCGRT is not encoded by the MHC.

ANIMAL MODEL

Akilesh et al. (2004) showed that mice lacking FcRn were resistant to transient inflammatory arthritis induced in wildtype mice upon transfer of serum from arthritic K/BxN mice, which are universally susceptible to autoimmune arthritis due to pathogenic anti-GPI (172400) IgG antibodies. K/BxN mice deficient in FcRn had significantly delaye ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601437 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).