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Fc fragment of IgG receptor and transporter

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2985

Nomenclature: Fc fragment of IgG receptor and transporter

Abbreviated Name: FcRn

Family: Immunoglobulin C1-set domain-containing proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 365 19q13.33 FCGRT Fc gamma receptor and transporter
Mouse 1 365 7 29.12 cM Fcgrt Fc fragment of IgG receptor and transporter
Rat 1 366 1q22 Fcgrt Fc gamma receptor and transporter
Previous and Unofficial Names Click here for help
Fc receptor, IgG, alpha chain transporter | Fc receptor | Fc fragment of IgG, receptor, transporter, alpha | heavy chain of the major histocompatibility complex class I-like Fc receptor | IgG receptor FcRn large subunit p51 | neonatal Fc receptor
Database Links Click here for help
Alphafold P55899 (Hs), Q61559 (Mm), P13599 (Rn)
ChEMBL Target CHEMBL5966 (Hs)
Ensembl Gene ENSG00000104870 (Hs), ENSMUSG00000003420 (Mm), ENSRNOG00000020583 (Rn)
Entrez Gene 2217 (Hs), 14132 (Mm), 29558 (Rn)
Human Protein Atlas ENSG00000104870 (Hs)
KEGG Gene hsa:2217 (Hs), mmu:14132 (Mm), rno:29558 (Rn)
OMIM 601437 (Hs)
Pharos P55899 (Hs)
RefSeq Nucleotide NM_004107 (Hs), NM_010189 (Mm), NM_033351 (Rn)
RefSeq Protein NP_004098 (Hs), NP_034319 (Mm), NP_203502 (Rn)
UniProtKB P55899 (Hs), Q61559 (Mm), P13599 (Rn)
Wikipedia FCGRT (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M.
PDB Id:  5WHK
Ligand:  DX-2507
Resolution:  2.5Å
Species:  Human
References:  4

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
DX-2507 Peptide Primary target of this compound Immunopharmacology Ligand Hs Antagonist 8.7 pKd 7
⤷ pKd 8.7 (Kd 1.8x10-9 M) [7]
Description: Binding affinity at acidic pH (6.0).
rozanolixizumab Peptide Approved drug Immunopharmacology Ligand Hs Binding ~8.2 – 8.7 pKd 2
⤷ pKd ~8.2 – 8.7 (Kd ~6x10-9 – 2x10-9 M) [2]
Description: In a cell- based in vitro assay using neutral buffer. Note this affinity range is for the 01519.g57 Fab or PEGylated Fab fragment, not the intact IgG4P antibody.
ziltivekimab Peptide Hs Binding 6.7 pKd 1
⤷ pKd 6.7 (Kd 2.26x10-7 M) [1]
ziltivekimab Peptide Monkey Binding 6.4 pKd 1
⤷ pKd 6.4 (Kd 3.65x10-7 M) [1]
Description: Binding affinity for cynomolgus monkey FcRn
efgartigimod alfa Peptide Approved drug Immunopharmacology Ligand Hs Binding - - 8
⤷ [8]
Antibody Comments
The FcRn binding affinity (Kd) of DX-2507 at neutral pH is 2 nM [7].
Immunopharmacology Comments
FcRn is important for developing immunity in the fetus and neonate (transporting IgG from mother to fetus and neonate for passive immunity) [3], for the development of adaptive immunity, and for regulating IgG levels (protecting IgG catabolism) in the mature immune system [5]. FcRn expression is upregulated by TNF-α (a proinflammatory cytokine) and downregulated by IFN-γ (an anti-inflammatory cytokine) [6]. In some autoimmune diseases levels of pathogenic IgG autoantibodies are elevated, and their long half-lives and prolonged action are a result of FcRn-mediated protection from degradation. For this reason inhibition of FcRn is viewed as an attractive clinical intervention for IgG-mediated autoimmune diseases [5-6]. FcRn antagonism may also be a strategy applicable to the management of neutralising anti-drug antibodies that can develop in patients receiving biologic/enzyme replacement therapies. Examples of anti-FcRn therapeutics in development pipelines include rozanolixizumab (Phase 2; UCB Pharma), efgartigimod alfa (Phase 2; Argenx), M281 (nipocalimab; Phase 2; Momenta Pharmaceuticals), SYNT001 (Phase 1; Syntimmune) and DX-2507 (preclinical; Shire).
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Antigen presentation
Immuno Process:  Cellular signalling

References

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1. Finch DK, Sleeman MA, Moisan J, Ferraro F, Botterell S, Campbell J, Cochrane D, Cruwys S, England E, Lane S et al.. (2011) Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics. J Mol Biol, 411 (4): 791-807. [PMID:21723291]

2. Finney HM, Lawson ADG, Shaw SG, Smith BJ, Tyson KL, Kevorkian L. (2014) Anti-fcrn antibodies. Patent number: WO2014019727. Assignee: Ucb Pharma S.A.. Priority date: 14/05/2012. Publication date: 06/02/2014.

3. Jones EA, Waldmann TA. (1972) The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest, 51 (11): 2916-27. [PMID:5080417]

4. Kenniston JA, Taylor BM, Conley GP, Cosic J, Kopacz KJ, Lindberg AP, Comeau SR, Atkins K, Bullen J, TenHoor C et al.. (2017) Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody. J Biol Chem, 292 (42): 17449-17460. [PMID:28878017]

5. Kuo TT, Aveson VG. (2011) Neonatal Fc receptor and IgG-based therapeutics. MAbs, 3 (5): 422-30. [PMID:22048693]

6. Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer WI, Blumberg RS. (2010) Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol, 30 (6): 777-89. [PMID:20886282]

7. Nixon AE, Chen J, Sexton DJ, Muruganandam A, Bitonti AJ, Dumont J, Viswanathan M, Martik D, Wassaf D, Mezo A et al.. (2015) Fully human monoclonal antibody inhibitors of the neonatal fc receptor reduce circulating IgG in non-human primates. Front Immunol, 6: 176. [PMID:25954273]

8. Ulrichts P, Cousin T, Dreier T, de Haard H, Leupin N. (2016) Argx-113, a Novel Fc-Based Approach for Antibody-Induced Pathologies Such As Primary Immune Thrombocytopenia. Blood, 128: 4919.

How to cite this page

Immunoglobulin C1-set domain-containing proteins: Fc fragment of IgG receptor and transporter. Last modified on 02/06/2021. Accessed on 06/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2985.