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Gene Review

FCGR1A  -  Fc fragment of IgG, high affinity Ia,...

Homo sapiens

Synonyms: CD64, CD64A, FCG1, FCGR1, FCRI, ...
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Disease relevance of FCGR1A


High impact information on FCGR1A

  • The high affinity receptor that binds the Fc domain of immunoglobulin G (IgG) subclasses 1 and 3 (Fc gamma RI) mediates important immune defense functions by inducing cell surface changes on human leukocytes [6].
  • In this article, we document direct high affinity binding of Fc gamma RI to the actin filament cross-linking protein, actin-binding protein (ABP) [6].
  • The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis [7].
  • Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fc gamma receptor gene (Fc gamma RI) [8].
  • Neutralization of interleukin 6, a cytokine present in SFs which is known to activate Stat3, abolished the activation of Stat-SF and inhibited the induction of Fc gamma RI expression by SFs [9].

Chemical compound and disease context of FCGR1A


Biological context of FCGR1A


Anatomical context of FCGR1A


Associations of FCGR1A with chemical compounds

  • Treatment with dexamethasone decreased Fc gamma RI expression by 39%, and also inhibited by 40% the increase induced by interferon-gamma [19].
  • In the present report we demonstrate that replacement of contact residues for galactose on the alpha(1-6) arm does not affect Fc gamma RI and Fc gamma RII recognition while replacement of Asp 265, a contact for a 'core' N-acetylglucosamine residue, results in a loss of Fc gamma RI and Fc gamma RII recognition [25].
  • Such rapid modulation of the high-affinity Fc gamma RI receptor by integrin cross-linking may reflect the requirement for rapid up-regulation of PMN effector functions, after interaction with endothelial cells, platelets or bacteria [26].
  • Macrophages were exposed to green fluorescent 1-micron polystyrene beads before labeling for Fc gamma RI, Fc gamma R-II, and Fc gamma R-III, respectively, with 32.2, 2E1, and 3G8 monoclonal antibodies (MoAbs) and a phycoerythrin (PE)-conjugated secondary Ab to permit dual-channel analysis of fluorescence intensity by FACS [27].
  • The results shown here demonstrate a distinct, indirect mechanism of cross-modulation between cytokine and steroid receptor signaling that integrates Stat1 and GR pathways with cell type-specific PU.1 transcription factor in the regulation of Fc gamma RI gene transcription [28].

Physical interactions of FCGR1A


Enzymatic interactions of FCGR1A


Regulatory relationships of FCGR1A

  • MHC class II Ag, and Fc gamma RI are both upregulated in the presence of IFN-gamma [35].
  • The potential of CD33 to function as an inhibitory receptor was demonstrated by its ability to down-regulate CD64-induced calcium mobilization in U937 [36].
  • Assays of STAT1 function in M. tuberculosis-treated cells also revealed no defect in activation of a minimal gamma-activated sequence construct or STAT1 recruitment to and binding at the endogenous CD64 promoter [37].
  • Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fc gamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells [38].
  • GR activated the natural Fc gamma RI promoter construct, and this response required both Stat1 and the Ets family transcription factor PU [28].

Other interactions of FCGR1A

  • Northern analysis of CD64 and p47 phox mRNAs confirmed the findings with the PCR method [39].
  • For example, the Fc gamma receptors Fc gamma RI and Fc gamma RIIIA induce signaling largely by association with a gamma subunit containing a conserved cytoplasmic motif (ITAM) whose tyrosines are phosphorylated following receptor stimulation [40].
  • Although Fc gamma RIIA utilizes tyrosines within its own cytoplasmic domain for signaling while Fc gamma RI utilizes the cytoplasmic tyrosines of its associated gamma subunit, our results indicate sharing of several proteins for signaling in monocytes by these Fc receptors [41].
  • In contrast to U937 cells, TNF-alpha did not enhance significantly Fc gamma RI expression on human monocytes [42].
  • FCGR1B was found at 1p12, whereas both FCGR1A and FCGR1C were localized to 1q21 [43].

Analytical, diagnostic and therapeutic context of FCGR1A


  1. Involvement of the high-affinity receptor for IgG (Fc gamma RI; CD64) in enhanced tumor cell cytotoxicity of neutrophils during granulocyte colony-stimulating factor therapy. Valerius, T., Repp, R., de Wit, T.P., Berthold, S., Platzer, E., Kalden, J.R., Gramatzki, M., van de Winkel, J.G. Blood (1993) [Pubmed]
  2. Influence of glutamine on the phenotype and function of human monocytes. Spittler, A., Winkler, S., Götzinger, P., Oehler, R., Willheim, M., Tempfer, C., Weigel, G., Függer, R., Boltz-Nitulescu, G., Roth, E. Blood (1995) [Pubmed]
  3. Isolation and expression of functional high-affinity Fc receptor complementary DNAs. Allen, J.M., Seed, B. Science (1989) [Pubmed]
  4. Involvement of Fc gamma RI (CD64) in the mechanism of HIV-1 inhibition by polyclonal IgG purified from infected patients in cultured monocyte-derived macrophages. Holl, V., Hemmerter, S., Burrer, R., Schmidt, S., Bohbot, A., Aubertin, A.M., Moog, C. J. Immunol. (2004) [Pubmed]
  5. Differential Enhancement of Dengue Virus Immune Complex Infectivity Mediated by Signaling-Competent and Signaling-Incompetent Human Fc{gamma}RIA (CD64) or Fc{gamma}RIIA (CD32). Rodrigo, W.W., Jin, X., Blackley, S.D., Rose, R.C., Schlesinger, J.J. J. Virol. (2006) [Pubmed]
  6. Ligand-sensitive binding of actin-binding protein to immunoglobulin G Fc receptor I (Fc gamma RI). Ohta, Y., Stossel, T.P., Hartwig, J.H. Cell (1991) [Pubmed]
  7. Impaired function of macrophage Fc gamma receptors in end-stage renal disease. Ruiz, P., Gomez, F., Schreiber, A.D. N. Engl. J. Med. (1990) [Pubmed]
  8. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Larner, A.C., David, M., Feldman, G.M., Igarashi, K., Hackett, R.H., Webb, D.S., Sweitzer, S.M., Petricoin, E.F., Finbloom, D.S. Science (1993) [Pubmed]
  9. Activation of monocyte effector genes and STAT family transcription factors by inflammatory synovial fluid is independent of interferon gamma. Sengupta, T.K., Chen, A., Zhong, Z., Darnell, J.E., Ivashkiv, L.B. J. Exp. Med. (1995) [Pubmed]
  10. Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells. Wagner, C., Deppisch, R., Denefleh, B., Hug, F., Andrassy, K., Hänsch, G.M. Shock (2003) [Pubmed]
  11. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility. Zhang, X., Yee, D. Cancer Res. (2002) [Pubmed]
  12. Heterodimerization of Insulin-like Growth Factor Receptor/Epidermal Growth Factor Receptor and Induction of Survivin Expression Counteract the Antitumor Action of Erlotinib. Morgillo, F., Woo, J.K., Kim, E.S., Hong, W.K., Lee, H.Y. Cancer Res. (2006) [Pubmed]
  13. Insulin-like growth factor-I-mediated neurite outgrowth in vitro requires mitogen-activated protein kinase activation. Kim, B., Leventhal, P.S., Saltiel, A.R., Feldman, E.L. J. Biol. Chem. (1997) [Pubmed]
  14. Insulin-like growth factor receptor levels are regulated by cell density and by long term estrogen deprivation in MCF7 human breast cancer cells. Stephen, R.L., Shaw, L.E., Larsen, C., Corcoran, D., Darbre, P.D. J. Biol. Chem. (2001) [Pubmed]
  15. Localization of FCGR1 encoding Fcgamma receptor class I in primates: molecular evidence for two pericentric inversions during the evolution of human chromosome 1. Maresco, D.L., Blue, L.E., Culley, L.L., Kimberly, R.P., Anderson, C.L., Theil, K.S. Cytogenet. Cell Genet. (1998) [Pubmed]
  16. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. Shields, R.L., Namenuk, A.K., Hong, K., Meng, Y.G., Rae, J., Briggs, J., Xie, D., Lai, J., Stadlen, A., Li, B., Fox, J.A., Presta, L.G. J. Biol. Chem. (2001) [Pubmed]
  17. IFN-gamma induces expression of Fc gamma RIII (CD16) on human eosinophils. Hartnell, A., Kay, A.B., Wardlaw, A.J. J. Immunol. (1992) [Pubmed]
  18. The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes. Fanger, N.A., Cosman, D., Peterson, L., Braddy, S.C., Maliszewski, C.R., Borges, L. Eur. J. Immunol. (1998) [Pubmed]
  19. Modulation of human mononuclear phagocyte Fc gamma RII mRNA and protein. Comber, P.G., Rossman, M.D., Rappaport, E.F., Chien, P., Hogarth, P.M., Schreiber, A.D. Cell. Immunol. (1989) [Pubmed]
  20. Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor. Repp, R., Valerius, T., Sendler, A., Gramatzki, M., Iro, H., Kalden, J.R., Platzer, E. Blood (1991) [Pubmed]
  21. Human basophils selectively express the Fc gamma RII (CDw32) subtype of IgG receptor. Anselmino, L.M., Perussia, B., Thomas, L.L. J. Allergy Clin. Immunol. (1989) [Pubmed]
  22. Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines. Boltz-Nitulescu, G., Willheim, M., Spittler, A., Leutmezer, F., Tempfer, C., Winkler, S. J. Leukoc. Biol. (1995) [Pubmed]
  23. CRP promotes monocyte-endothelial cell adhesion via Fcgamma receptors in human aortic endothelial cells under static and shear flow conditions. Devaraj, S., Davis, B., Simon, S.I., Jialal, I. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  24. The uptake of LDL-IC by human macrophages: predominant involvement of the Fc gamma RI receptor. Lopes-Virella, M.F., Binzafar, N., Rackley, S., Takei, A., La Via, M., Virella, G. Atherosclerosis (1997) [Pubmed]
  25. Recognition sites on human IgG for Fc gamma receptors: the role of glycosylation. Jefferis, R., Lund, J., Goodall, M. Immunol. Lett. (1995) [Pubmed]
  26. Rapid and prominent up-regulation of high-affinity receptor for immunoglobulin G (Fc gamma RI) by cross-linking of beta 2 integrins on polymorphonuclear leukocytes. Takano, K., Kaganoi, J., Yamamoto, K., Takahashi, A., Kido, T., Sasada, M. Int. J. Hematol. (2000) [Pubmed]
  27. Paracrine downregulation of Fc gamma RIII in human monocyte-derived macrophages induced by phagocytosis of nonopsonized particles. Liao, G., Simone, J., Simon, S.R. Blood (1994) [Pubmed]
  28. Cooperation among Stat1, glucocorticoid receptor, and PU.1 in transcriptional activation of the high-affinity Fc gamma receptor I in monocytes. Aittomäki, S., Pesu, M., Groner, B., Jänne, O.A., Palvimo, J.J., Silvennoinen, O. J. Immunol. (2000) [Pubmed]
  29. Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn. Wang, A.V., Scholl, P.R., Geha, R.S. J. Exp. Med. (1994) [Pubmed]
  30. Protein tyrosine phosphatase inhibitors in Fc gamma RI-induced myeloid oxidant signaling. Erdreich-Epstein, A., Liu, M., Liu, Y., Durden, D.L. Exp. Cell Res. (1997) [Pubmed]
  31. Histidine-rich glycoprotein binds to DNA and Fc gamma RI and potentiates the ingestion of apoptotic cells by macrophages. Gorgani, N.N., Smith, B.A., Kono, D.H., Theofilopoulos, A.N. J. Immunol. (2002) [Pubmed]
  32. Fc receptors and immunoglobulin binding factors. Fridman, W.H. FASEB J. (1991) [Pubmed]
  33. C-reactive protein binds to Fc gamma RI in transfected COS cells. Marnell, L.L., Mold, C., Volzer, M.A., Burlingame, R.W., Du Clos, T.W. J. Immunol. (1995) [Pubmed]
  34. Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. Liao, F., Shin, H.S., Rhee, S.G. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  35. IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10. te Velde, A.A., de Waal Malefijt, R., Huijbens, R.J., de Vries, J.E., Figdor, C.G. J. Immunol. (1992) [Pubmed]
  36. Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. Paul, S.P., Taylor, L.S., Stansbury, E.K., McVicar, D.W. Blood (2000) [Pubmed]
  37. Mycobacterium tuberculosis exerts gene-selective inhibition of transcriptional responses to IFN-gamma without inhibiting STAT1 function. Kincaid, E.Z., Ernst, J.D. J. Immunol. (2003) [Pubmed]
  38. Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fc gamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells. Notter, M., Ludwig, W.D., Bremer, S., Thiel, E. Blood (1993) [Pubmed]
  39. Effects of gamma-interferon on human neutrophils: protection from deterioration on storage. Klebanoff, S.J., Olszowski, S., Van Voorhis, W.C., Ledbetter, J.A., Waltersdorph, A.M., Schlechte, K.G. Blood (1992) [Pubmed]
  40. Fc gamma receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of signaling for phagocytosis. Kim, M.K., Pan, X.Q., Huang, Z.Y., Hunter, S., Hwang, P.H., Indik, Z.K., Schreiber, A.D. Clin. Immunol. (2001) [Pubmed]
  41. Activation of three classes of nonreceptor tyrosine kinases following Fc gamma receptor crosslinking in human monocytes. Pan, X.Q., Darby, C., Indik, Z.K., Schreiber, A.D. Clin. Immunol. (1999) [Pubmed]
  42. Influence of tumour necrosis factor-alpha on the expression of Fc IgG and IgA receptors, and other markers by cultured human blood monocytes and U937 cells. Gessl, A., Willheim, M., Spittler, A., Agis, H., Krugluger, W., Boltz-Nitulescu, G. Scand. J. Immunol. (1994) [Pubmed]
  43. The three genes of the human FCGR1 gene family encoding Fc gamma RI flank the centromere of chromosome 1 at 1p12 and 1q21. Maresco, D.L., Chang, E., Theil, K.S., Francke, U., Anderson, C.L. Cytogenet. Cell Genet. (1996) [Pubmed]
  44. Human high-affinity Fc gamma RI (CD64) gene mapped to chromosome 1q21.2-q21.3 by fluorescence in situ hybridization. Takai, S., Kasama, M., Yamada, K., Kai, N., Hirayama, N., Namiki, H., Taniyama, T. Hum. Genet. (1994) [Pubmed]
  45. FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. Cheung, N.K., Sowers, R., Vickers, A.J., Cheung, I.Y., Kushner, B.H., Gorlick, R. J. Clin. Oncol. (2006) [Pubmed]
  46. Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma. Okayama, Y., Kirshenbaum, A.S., Metcalfe, D.D. J. Immunol. (2000) [Pubmed]
  47. Mature polymorphonuclear leukocytes express high-affinity receptors for IgG (Fc gamma RI) after stimulation with granulocyte colony-stimulating factor (G-CSF). Gericke, G.H., Ericson, S.G., Pan, L., Mills, L.E., Guyre, P.M., Ely, P. J. Leukoc. Biol. (1995) [Pubmed]
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