FCGR2B

FCGR2B
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2FCB, 3WJJ,%%s3WJL
Identifikatori
Aliasi	FCGR2B
Vanjski ID-jevi	OMIM: 604590 MGI: 95499 HomoloGene: 2974 GeneCards: FCGR2B
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	161,678,654 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	170,804,116 bp
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • IgG binding; • amyloid-beta binding; • low-affinity IgG receptor activity; • GO:0032403 protein-containing complex binding; • transmembrane signaling receptor activity;
Ćelijska komponenta	• integral component of membrane; • ćelijska membrana; • membrana; • integral component of plasma membrane; • external side of plasma membrane; • dendritična kičma; • cell body; • citoplazma;
Biološki proces	• GO:0022415 viral process; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor; • GO:0072468 Transdukcija signala; • regulation of immune response; • negative regulation of type I hypersensitivity; • negative regulation of antibody-dependent cellular cytotoxicity; • follicular dendritic cell activation; • mature B cell differentiation involved in immune response; • follicular B cell differentiation; • immune complex clearance by monocytes and macrophages; • negative regulation of dendritic cell antigen processing and presentation; • regulation of B cell antigen processing and presentation; • negative regulation of immunoglobulin production; • regulation of adaptive immune response; • negative regulation of acute inflammatory response to antigenic stimulus; • positive regulation of humoral immune response; • negative regulation of humoral immune response mediated by circulating immunoglobulin; • receptor-mediated endocytosis; • phagocytosis, engulfment; • defense response; • inflammatory response; • response to bacterium; • regulation of signaling receptor activity; • immunoglobulin mediated immune response; • antigen processing and presentation of exogenous peptide antigen via MHC class II; • cerebellum development; • negative regulation of B cell proliferation; • negative regulation of interleukin-10 production; • Fc-gamma receptor signaling pathway involved in phagocytosis; • negative regulation of macrophage activation; • negative regulation of cytotoxic T cell degranulation; • regulation of innate immune response; • mast cell activation; • positive regulation of JNK cascade; • negative regulation of phagocytosis; • positive regulation of phagocytosis; • negative regulation of immune response; • negative regulation of B cell receptor signaling pathway; • negative regulation of B cell activation; • cellular response to molecule of bacterial origin; • regulation of immune complex clearance by monocytes and macrophages; • positive regulation of neuron death; • negative regulation of neutrophil activation; • regulation of dendritic spine maintenance; • cellular response to amyloid-beta; • positive regulation of response to endoplasmic reticulum stress; • negative regulation of dendritic cell differentiation;
	Izvori:Amigo / QuickGO
Ortolozi
	2213
	14130
	ENSG00000072694
	ENSMUSG00000026656
	P31994; P31995
	P08101
	NM_001002273; NM_001002274; NM_001002275; NM_001190828; NM_004001
	NM_001077189; NM_010187
NP_001002273; NP_001002274; NP_001002275; NP_001177757; NP_003992;
	NP_963857
	NP_001070657; NP_034317
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Fc-fragment IgG receptora IIb jest protein koji je kod ljudi kodiran genom FCGR2B sa hromosoma 1. Za Fc-regiju imunoglobulina gama (IgG) niski su afiniteti inhibitornih receptora. FCGR2B učestvuje u fagocitozi imunskih kompleksa i u regulaciji proizvodnje antitijela putem B-limfocita.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 310 aminokiselina, a molekulska težina 34.044 Da.^[6]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MGILSFLPVL	ATESDWADCK	SPQPWGHMLL	WTAVLFLAPV	AGTPAAPPKA
VLKLEPQWIN	VLQEDSVTLT	CRGTHSPESD	SIQWFHNGNL	IPTHTQPSYR
FKANNNDSGE	YTCQTGQTSL	SDPVHLTVLS	EWLVLQTPHL	EFQEGETIVL
RCHSWKDKPL	VKVTFFQNGK	SKKFSRSDPN	FSIPQANHSH	SGDYHCTGNI
GYTLYSSKPV	TITVQAPSSS	PMGIIVAVVT	GIAVAAIVAA	VVALIYCRKK
RISALPGYPE	CREMGETLPE	KPANPTNPDE	ADKVGAENTI	TYSLLMHPDA
LEEPDDQNRI

Struktura

Postoje dva glavna oblika FCGR2B (FCGR2B1 i FCGR2B2) i oni su stvoreni mehanizmom prerade iRNK, što rezultira uključivanjem (FCGR2B1) ili isključenjem (FCGR2B2) sekvence egzona C1. Prisustvo sekvence egzona C1 (u FCGR2B1) dovodi do vezivanja za membranu B-ćelija, dok njeno odsustvo (u FCGR2B2) omogućava brzu internalizaciju receptora u mijeloidnim ćelijama. Oba oblika sadrže Inhibitorni motiv zasnovan na imunoreceptoru tirozina (ITIM) u svojim citoplazmatskim regijama. Vanćelijski domeni su 95% identični domenima FCGR2A i skoro potpuno identični FCGR2C (ostali članovi porodice CD32).^[7]

Ekaspresija

FCGR2B1 je visoko eksprimiran u B-ćelijama, a njegova iRNK je također identificirana na nižim nivoima na monocitiima. FCGR2B2 je visoko izražen na bazofilima i na niskim nivoima na monocitima. Regulacija ekspresije citokina je pozitivna u slučaju IL-10 i IL-6, a negativna u slučaju TNF-α , C5a i IFN-γ.^[7]

Funkcija

Receptor inhibira funkcije aktiviranja FcγR, kao što je fagocitoza i proupalno oslobađanje citokina, uglavnom grupiranjem FCGR2B s različitim aktivirajućim FCGR receptorima ili sa BCR pomoću imunskih kompleksa.^[7]^[8]

Fosforilizirani ITIM FcγRIIB regrutuje inozitol-fosfataze SHIP1 i SHIP2, koje inhibiraju aktivaciju Ras, smanjujući aktivnost MAPK i smanjujući funkciju PLCγ i dovode do smanjene aktivacije PKC. Inhibicija puta MAP-kinaze, zajedno sa antiapoptotskom kinazom Akt, može negativno uticati na proliferaciju i preživljavanje ćelija.^[7]

FCGR2B regulira aktivaciju B-ćelija povećanjem praga aktivacije BCR i potiskivanjem prezentacije antigena posredovane B– i T-ćelijama preko ITIM-ovisnog inhibitornog mehanizma.^[8] Ligacija FCGR2B na B-ćelijama smanjuje regulaciju antitijela, sprečavajući membransku organizaciju BCR i CD19 i promovira apoptozu. Koligacija FCGR2B na dendritskim ćelijama inhibira sazrijevanje i blokira aktivaciju ćelija.^[7] Negativna regulatorna uloga FCGRIIB molekula nije ograničena na BCR-indukovanu aktivaciju B-ćelija, već je također funkcionalna na drugim putevima aktivacije B-ćelija posredovane putem CD40 i IL-4.^[9]

Ekspresija FCGR2B na folikulskim dendritskim ćelijama (FDCs) je važna za hvatanje imunskih kompleksa koji sadrže antigen koji su neophodni za odgovor germinalnog centra.^[8]

FCGR2B je prisutan na neleukocitnim ćelijama, uključujući glatke mišiće disajnih puteva i sinusoidne endotelne ćelije jetre, gdje su mali imunski kompleksi internalizovani i inhibiraju proupalnu signalizaciju.^[7]

Autoimunost

FCGR2B je jedan od gena za koje se smatra da utiču na osjetljivost na nekoliko autoimunskih bolesti kod ljudi. Njegova smanjena funkcija povezana je sa sistemskim eritemskim lupusom, reumatoidnim artritisom, Goodpastureovom bolešću, multiplom sklerozom i drugim.^[8]

FCGR2B može biti meta za terapiju monoklonskim antitijelima za autoimunske i maligne bolesti.^[8]^[10]^[11]

Također pogledajte

CD32

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000072694 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026656 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "FCGR2B Fc fragment of IgG receptor IIb [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 14. 6. 2019.
^ "UniProt, P31994" (jezik: en.). Pristupljeno 10. 12. 2021.CS1 održavanje: nepoznati jezik (link)
^ ^a ^b ^c ^d ^e ^f Anania JC, Chenoweth AM, Wines BD, Hogarth PM (19. 3. 2019). "The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease". Frontiers in Immunology. 10: 464. doi:10.3389/fimmu.2019.00464. PMC 6433993. PMID 30941127.
^ ^a ^b ^c ^d ^e Smith, Kenneth G. C.; Clatworthy, Menna R. (6. 8. 2010). "Erratum: FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications". Nature Reviews Immunology. 10 (9): 674. doi:10.1038/nri2821. ISSN 1474-1733.
^ Horejs-Hoeck J, Hren A, Mudde GC, Woisetschläger M (juli 2005). "Inhibition of immunoglobulin E synthesis through Fc gammaRII (CD32) by a mechanism independent of B-cell receptor co-cross-linking". Immunology. 115 (3): 407–15. doi:10.1111/j.1365-2567.2005.02162.x. PMC 1782155. PMID 15946258.
^ Rankin CT, Veri MC, Gorlatov S, Tuaillon N, Burke S, Huang L, et al. (oktobar 2006). "CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma". Blood. 108 (7): 2384–91. doi:10.1182/blood-2006-05-020602. PMID 16757681.
^ Zhou P, Comenzo RL, Olshen AB, Bonvini E, Koenig S, Maslak PG, et al. (april 2008). "CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy". Blood. 111 (7): 3403–6. doi:10.1182/blood-2007-11-125526. PMC 2275009. PMID 18216299.

Dopunska literatura

Tsuchiya N, Kyogoku C (august 2005). "Role of Fc gamma receptor IIb polymorphism in the genetic background of systemic lupus erythematosus: insights from Asia". Autoimmunity. 38 (5): 347–52. doi:10.1080/08916930500123926. PMID 16227149. S2CID 37295376.
Engelhardt W, Geerds C, Frey J (juni 1990). "Distribution, inducibility and biological function of the cloned and expressed human beta Fc receptor II". European Journal of Immunology. 20 (6): 1367–77. doi:10.1002/eji.1830200624. PMID 2142460. S2CID 13498051.
Seki T (1989). "Identification of multiple isoforms of the low-affinity human IgG Fc receptor". Immunogenetics. 30 (1): 5–12. doi:10.1007/BF02421463. PMID 2526077. S2CID 23208039.
Brooks DG, Qiu WQ, Luster AD, Ravetch JV (oktobar 1989). "Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes". The Journal of Experimental Medicine. 170 (4): 1369–85. doi:10.1084/jem.170.4.1369. PMC 2189488. PMID 2529342.
Stuart SG, Simister NE, Clarkson SB, Kacinski BM, Shapiro M, Mellman I (decembar 1989). "Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium". The EMBO Journal. 8 (12): 3657–66. doi:10.1002/j.1460-2075.1989.tb08540.x. PMC 402048. PMID 2531080.
Stengelin S, Stamenkovic I, Seed B (april 1988). "Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning". The EMBO Journal. 7 (4): 1053–9. doi:10.1002/j.1460-2075.1988.tb02913.x. PMC 454434. PMID 3402431.
Engelhardt W, Matzke J, Schmidt RE (april 1995). "Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes". Immunobiology. 192 (5): 297–320. doi:10.1016/s0171-2985(11)80172-5. PMID 7649565.
D'Ambrosio D, Hippen KL, Minskoff SA, Mellman I, Pani G, Siminovitch KA, Cambier JC (april 1995). "Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1". Science. 268 (5208): 293–7. Bibcode:1995Sci...268..293D. doi:10.1126/science.7716523. PMID 7716523.
Warmerdam PA, van den Herik-Oudijk IE, Parren PW, Westerdaal NA, van de Winkel JG, Capel PJ (mart 1993). "Interaction of a human Fc gamma RIIb1 (CD32) isoform with murine and human IgG subclasses". International Immunology. 5 (3): 239–47. doi:10.1093/intimm/5.3.239. PMID 8466861.
Bewarder N, Weinrich V, Budde P, Hartmann D, Flaswinkel H, Reth M, Frey J (septembar 1996). "In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation". Molecular and Cellular Biology. 16 (9): 4735–43. doi:10.1128/MCB.16.9.4735. PMC 231474. PMID 8756631.
Sandilands GP, MacPherson SA, Burnett ER, Russell AJ, Downie I, MacSween RN (juni 1997). "Differential expression of CD32 isoforms following alloactivation of human T cells". Immunology. 91 (2): 204–11. doi:10.1046/j.1365-2567.1997.00241.x. PMC 1363848. PMID 9227318.
De SK, Venkateshan CN, Seth P, Gajdusek DC, Gibbs CJ (mart 1998). "Adenovirus-mediated human immunodeficiency virus-1 Nef expression in human monocytes/macrophages and effect of Nef on downmodulation of Fcgamma receptors and expression of monokines". Blood. 91 (6): 2108–17. doi:10.1182/blood.V91.6.2108. PMID 9490697.
Metes D, Ernst LK, Chambers WH, Sulica A, Herberman RB, Morel PA (april 1998). "Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene". Blood. 91 (7): 2369–80. doi:10.1182/blood.V91.7.2369. PMID 9516136.
Sondermann P, Huber R, Jacob U (mart 1999). "Crystal structure of the soluble form of the human fcgamma-receptor IIb: a new member of the immunoglobulin superfamily at 1.7 A resolution". The EMBO Journal. 18 (5): 1095–103. doi:10.1093/emboj/18.5.1095. PMC 1171201. PMID 10064577.
Muraille E, Bruhns P, Pesesse X, Daëron M, Erneux C (april 2000). "The SH2 domain containing inositol 5-phosphatase SHIP2 associates to the immunoreceptor tyrosine-based inhibition motif of Fc gammaRIIB in B cells under negative signaling". Immunology Letters. 72 (1): 7–15. doi:10.1016/S0165-2478(00)00162-0. PMID 10789675.
Pricop L, Redecha P, Teillaud JL, Frey J, Fridman WH, Sautès-Fridman C, Salmon JE (januar 2001). "Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines". Journal of Immunology. 166 (1): 531–7. doi:10.4049/jimmunol.166.1.531. PMID 11123333.
Lyden TW, Robinson JM, Tridandapani S, Teillaud JL, Garber SA, Osborne JM, et al. (mart 2001). "The Fc receptor for IgG expressed in the villus endothelium of human placenta is Fc gamma RIIb2". Journal of Immunology. 166 (6): 3882–9. doi:10.4049/jimmunol.166.6.3882. PMID 11238632.
Bharadwaj D, Mold C, Markham E, Du Clos TW (juni 2001). "Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis". Journal of Immunology. 166 (11): 6735–41. doi:10.4049/jimmunol.166.11.6735. PMID 11359830.
Jessup CF, Ridings J, Ho A, Nobbs S, Roberton DM, Macardle P, Zola H (juli 2001). "The Fc receptor for IgG (Fc gamma RII; CD32) on human neonatal B lymphocytes". Human Immunology. 62 (7): 679–85. doi:10.1016/S0198-8859(01)00257-9. PMID 11423173.

Vanjski linkovi

FCGR2B protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000072694 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026656 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] "FCGR2B Fc fragment of IgG receptor IIb [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 14. 6. 2019.

[UniProt-6] "UniProt, P31994" (jezik: en.). Pristupljeno 10. 12. 2021.CS1 održavanje: nepoznati jezik (link)

[:0-7] ^ ^a ^b ^c ^d ^e ^f Anania JC, Chenoweth AM, Wines BD, Hogarth PM (19. 3. 2019). "The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease". Frontiers in Immunology. 10: 464. doi:10.3389/fimmu.2019.00464. PMC 6433993. PMID 30941127.

[:1-8] Smith, Kenneth G. C.; Clatworthy, Menna R. (6. 8. 2010). "Erratum: FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications". Nature Reviews Immunology. 10 (9): 674. doi:10.1038/nri2821. ISSN 1474-1733.

[9] Horejs-Hoeck J, Hren A, Mudde GC, Woisetschläger M (juli 2005). "Inhibition of immunoglobulin E synthesis through Fc gammaRII (CD32) by a mechanism independent of B-cell receptor co-cross-linking". Immunology. 115 (3): 407–15. doi:10.1111/j.1365-2567.2005.02162.x. PMC 1782155. PMID 15946258.

[10] Rankin CT, Veri MC, Gorlatov S, Tuaillon N, Burke S, Huang L, et al. (oktobar 2006). "CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma". Blood. 108 (7): 2384–91. doi:10.1182/blood-2006-05-020602. PMID 16757681.

[11] Zhou P, Comenzo RL, Olshen AB, Bonvini E, Koenig S, Maslak PG, et al. (april 2008). "CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy". Blood. 111 (7): 3403–6. doi:10.1182/blood-2007-11-125526. PMC 2275009. PMID 18216299.

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