FCGR2B (Fc fragment of IgG, low affinity IIb, receptor (CD32))

2002-02-01   Mary Callanan , Dominique Leroux 

Lymphoma Research Group - Groupe de Recherche sur les Lymphomes - EMI0353, Institut Albert Bonniot, Université Joseph Fourier Grenoble 1, La Tronche 38706, France

Identity

HGNC
LOCATION
1q23.3
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CD32,CD32B,FCG2,FCGR2,FCGR2C,FcRII-c,IGFR2
FUSION GENES

DNA/RNA

Description

The FCGR2B gene spans a 15kb genomic region; Gene orientation : centromere - 3 FCGR2B 5 - telomere; 8 exons (denoted S1, S2, EC1, EC2, TM, IC1, IC2, IC3). S1 and S2 encode the signal peptide domain, EC1 and EC2 encode the extracellular domain, TM encodes the transmembrane domain and IC1, IC2, IC3 encode the intracytoplasmic region.

Transcription

1.7kb mRNA. Two alternately spliced mRNA exist in humans; FcgRIIb1 and FcgRIIb2 (a 19 aa insertion encoded by IC1 is present in b1 but not in b2).

Proteins

Note

called Fc gamma RIIB

Description

40kD transmembrane glycoprotein that possesses an intracytoplasmic Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) (encoded by IC3).

Expression

B, myeloid and mast cells.

Localisation

Transmembrane.

Function

Low affinity IgG Fc receptor. Founding member ITIM family of immune inhibitory receptors. Fc gamma RIIB functions to down-regulate activatory responses mediated by Immunoreceptor Tyrosine-based Inhibition Motif (ITAM) bearing receptors such as the B-cell receptor on B cells. For example, on B-cells, negative regulation of B-cell receptor activatory signalling is initiated through co-recruitment of BCR and Fc gamma RIIB to IgG/ immune complexes. This leads to tyrosyl phosphorylation of the Fc gamma RIIB ITIM motif / recruitment of the inositol phosphatase SHIP and activation of the adaptor protein Dok - these events ultimately lead to the inhibition of ITAM-dependant Ca++ mobilisation and cellular proliferation (reduced MAPK signalling), respectively.
A proapoptotic signal through the Fc gamma RIIB transmembrane sequence has been described in conditions of homo-aggregation of Fc gamma RII on murine B cells.

Homology

Contains two immunoglobulin-like C2 domains.

Implicated in

Entity name
1q21-23 rearrangements in NHL (Nnon-Hodgkins Lymphoma)
Disease
NHL (< 5% of cases with 1q21-23 breaks)
Prognosis
It is now known that cytogenetically determined 1q21-23 breaks can target a diversity of 1q21-23 genes. Early data has suggested a poor prognosis for 1q21 rearrangements in diffuse large cell lymphoma.
Cytogenetics
Deregulation of the FCGR2B gene by chromosomal translocation was first demonstrated in 3 NHL patients that showed a t(1;22)(q22;q22) in association with a t(14;18)(q32;q21). Two further cases of NHL with rearrangements affecting the FCGR2B region have since been identified. Both cases also showed t(14;18)(see below for description). This suggests a role for this deregulation in lymphoma progression.
Hybrid gene
Dysregulation of the FCGR2B gene has been identified as a consequence of a t(1;22)(q22;q11) (3 patients) and t(1;14)(q21;q32) (1 patient). The FCGR2B coding sequence and promoter region appear to remain intact in these translocations. The principal consequence is overexpression of the Fc gamma RIIb2 isoform of Fc gamma RIIB. Deregulation of FCGR2B most likely occurs as a consequence of Ig gene transcriptional enhancer activity. Other mechanisms may exist ; an NHL patient with dup(1)(q21q25) and rearrangement in the FCGR2B region has also been identified.
Fusion protein
None
Oncogenesis
Contribution of FCGR2B deregulation to lymphoma development or progression is currently not known.

Bibliography

Pubmed IDLast YearTitleAuthors
106184142000The IgG Fc receptor, FcgammaRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma.Callanan MB et al
117536462001Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas.Chen W et al
91436871997Fc receptor biology.Daëron M et al
110218042000Immune inhibitory receptors.Ravetch JV et al

Other Information

Locus ID:

NCBI: 2213
MIM: 604590
HGNC: 3618
Ensembl: ENSG00000072694

Variants:

dbSNP: 2213
ClinVar: 2213
TCGA: ENSG00000072694
COSMIC: FCGR2B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000072694ENST00000236937P31994
ENSG00000072694ENST00000358671P31994
ENSG00000072694ENST00000367961P31994

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Pathways

PathwaySourceExternal ID
B cell receptor signaling pathwayKEGGko04662
B cell receptor signaling pathwayKEGGhsa04662
Fc gamma R-mediated phagocytosisKEGGko04666
Fc gamma R-mediated phagocytosisKEGGhsa04666
PhagosomeKEGGko04145
PhagosomeKEGGhsa04145
Staphylococcus aureus infectionKEGGko05150
Staphylococcus aureus infectionKEGGhsa05150
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
MeaslesKEGGko05162
MeaslesKEGGhsa05162
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cellREACTOMER-HSA-198933

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA451743trastuzumabChemicalLiterature, MultilinkAnnotationnot associated18347005

References

Pubmed IDYearTitleCitations
183470052008Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer.303
161703232005Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts.105
161158112005FcgammaRIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling.78
169238492006Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE.76
174351652007Systemic lupus erythematosus-associated defects in the inhibitory receptor FcgammaRIIb reduce susceptibility to malaria.69
121152302002Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility.66
121152302002Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility.66
217468972011Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.62
175026662007Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human dendritic cells and monocytes induces a type I interferon response program.58
193096902009Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B.58

Citation

Mary Callanan ; Dominique Leroux

FCGR2B (Fc fragment of IgG, low affinity IIb, receptor (CD32))

Atlas Genet Cytogenet Oncol Haematol. 2002-02-01

Online version: http://atlasgeneticsoncology.org/gene/397/fcgr2b