ID FCG3B_HUMAN Reviewed; 233 AA. AC O75015; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2024, sequence version 3. DT 27-MAR-2024, entry version 204. DE RecName: Full=Low affinity immunoglobulin gamma Fc region receptor III-B; DE AltName: Full=Fc-gamma RIII-beta; DE Short=CD16-I {ECO:0000303|PubMed:1825220}; DE Short=Fc-gamma RIII; DE Short=Fc-gamma RIIIb; DE Short=FcRIII; DE Short=FcRIIIb; DE AltName: Full=FcR-10; DE AltName: Full=IgG Fc receptor III-1; DE AltName: CD_antigen=CD16b; DE Flags: Precursor; GN Name=FCGR3B; Synonyms=CD16B, FCG3, FCGR3, IGFR3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE FCGR3B*02), AND POLYMORPHISM. RX PubMed=2526846; DOI=10.1084/jem.170.2.481; RA Ravetch J.V., Perussia B.; RT "Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer RT cells and neutrophils. Cell type-specific expression of two genes that RT differ in single nucleotide substitutions."; RL J. Exp. Med. 170:481-497(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE FCGR3B*02), AND POLYMORPHISM. RC TISSUE=Placenta; RX PubMed=2967436; DOI=10.1038/333568a0; RA Simmons D., Seed B.; RT "The Fc gamma receptor of natural killer cells is a phospholipid-linked RT membrane protein."; RL Nature 333:568-570(1988). RN [3] RP ERRATUM OF PUBMED:2967436. RA Simmons D., Seed B.; RL Nature 340:662-662(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE FCGR3B*01), AND POLYMORPHISM. RC TISSUE=Leukocyte; RX PubMed=2521732; DOI=10.1073/pnas.86.3.1013; RA Peltz G.A., Grundy H.O., Lebo R.V., Yssel H., Barsh G.S., Moore K.W.; RT "Human Fc-gamma-RIII: cloning, expression, and identification of the RT chromosomal locus of two Fc receptors for IgG."; RL Proc. Natl. Acad. Sci. U.S.A. 86:1013-1017(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-65. RX PubMed=2525780; DOI=10.1073/pnas.86.13.5079; RA Scallon B.J., Scigliano E., Freedman V.H., Miedel M.C., Pan Y.C., RA Unkeless J.C., Kochan J.P.; RT "A human immunoglobulin G receptor exists in both polypeptide-anchored and RT phosphatidylinositol-glycan-anchored forms."; RL Proc. Natl. Acad. Sci. U.S.A. 86:5079-5083(1989). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE FCGR3B*02), AND POLYMORPHISM. RC TISSUE=Peripheral blood; RX PubMed=15245367; DOI=10.1111/j.1399-0039.2004.00259.x; RA Bertrand G., Duprat E., Lefranc M.-P., Marti J., Coste J.; RT "Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT RT standardized description of FCGR3B alleles."; RL Tissue Antigens 64:119-131(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 (ALLELE FCGR3B*02), AND RP POLYMORPHISM. RC TISSUE=Placenta; RX PubMed=7836402; DOI=10.1074/jbc.270.3.1350; RA Gessner J.E., Grussenmeyer T., Kolanus W., Schmidt R.E.; RT "The human low affinity immunoglobulin G Fc receptor III-A and III-B genes. RT Molecular characterization of the promoter regions."; RL J. Biol. Chem. 270:1350-1361(1995). RN [9] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-203. RX PubMed=1825220; RA Lanier L.L., Yu G., Phillips J.H.; RT "Analysis of Fc gamma RIII (CD16) membrane expression and association with RT CD3 zeta and Fc epsilon RI-gamma by site-directed mutation."; RL J. Immunol. 146:1571-1576(1991). RN [10] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH IGG1 FC, AND RP DISULFIDE BOND. RX PubMed=10917521; DOI=10.1038/35018508; RA Sondermann P., Huber R., Oosthuizen V., Jacob U.; RT "The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII RT complex."; RL Nature 406:267-273(2000). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 19-192, AND DISULFIDE BONDS. RX PubMed=11021536; DOI=10.1016/s1074-7613(00)00038-8; RA Zhang Y., Boesen C.C., Radaev S., Brooks A.G., Fridman W.H., RA Sautes-Fridman C., Sun P.D.; RT "Crystal structure of the extracellular domain of a human Fc gamma RIII."; RL Immunity 13:387-395(2000). RN [12] RP POLYMORPHISM, AND VARIANT FCGR3B*03 ASP-78. RX PubMed=9028335; RA Bux J., Stein E.L., Bierling P., Fromont P., Clay M., Stroncek D., RA Santoso S.; RT "Characterization of a new alloantigen (SH) on the human neutrophil Fc RT gamma receptor IIIb."; RL Blood 89:1027-1034(1997). CC -!- FUNCTION: Receptor for the Fc region of immunoglobulins gamma. Low CC affinity receptor. Binds complexed or aggregated IgG and also monomeric CC IgG. Contrary to III-A, is not capable to mediate antibody-dependent CC cytotoxicity and phagocytosis. May serve as a trap for immune complexes CC in the peripheral circulation which does not activate neutrophils. CC -!- SUBUNIT: Monomer. Interacts with INPP5D/SHIP1 (By similarity). CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1825220}; CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:1825220}. Secreted. CC Note=Secreted after cleavage. CC -!- TISSUE SPECIFICITY: Expressed specifically by polymorphonuclear CC leukocytes (neutrophils). Also expressed by stimulated eosinophils. CC -!- PTM: Glycosylated. Glycosylation plays an inhibitory role in the CC interaction with IgG3. CC -!- PTM: The soluble form is produced by a proteolytic cleavage. CC -!- POLYMORPHISM: There are three allelic forms of FCGR3B: FCGR3B*01 (HNA- CC 1a, NA-1), FCGR3B*02 (HNA-1b, NA-2) and FCGR3B*03 (HNA-1c, SH). CC FCGR3B*01 and FCGR3B*02 are detectable with antibodies against the CC biallelic neutrophil-specific antigen system NA. The more active CC FCGR3B*01 allele has been associated with severe renal disease in CC certain forms of systemic vasculitides. {ECO:0000269|PubMed:15245367, CC ECO:0000269|PubMed:2521732, ECO:0000269|PubMed:2526846, CC ECO:0000269|PubMed:2967436, ECO:0000269|PubMed:7836402, CC ECO:0000269|PubMed:9028335}. CC -!- MISCELLANEOUS: Encoded by one of two nearly identical genes: FCGR3A and CC FCGR3B (Shown here) which are expressed in a tissue-specific manner. CC The 'Phe-203' in FCGR3A determines the transmembrane domains whereas CC the Ser-203 in FCGR3B determines the GPI-anchoring. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X16863; CAA34753.1; -; mRNA. DR EMBL; X07934; CAA30758.1; -; mRNA. DR EMBL; J04162; AAA35881.1; -; mRNA. DR EMBL; M24854; AAA53507.1; -; mRNA. DR EMBL; AJ581669; CAE46408.1; -; mRNA. DR EMBL; AL451067; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z46223; CAA86296.1; -; Genomic_DNA. DR CCDS; CCDS41433.1; -. DR PIR; JU0284; JU0284. DR RefSeq; NP_000561.3; NM_000570.4. DR RefSeq; NP_001231682.1; NM_001244753.1. DR RefSeq; NP_001257964.1; NM_001271035.1. DR RefSeq; NP_001257965.1; NM_001271036.1. DR RefSeq; NP_001257966.1; NM_001271037.1. DR PDB; 1E4J; X-ray; 2.50 A; A=18-193. DR PDB; 1E4K; X-ray; 3.20 A; C=18-193. DR PDB; 1FNL; X-ray; 1.80 A; A=19-192. DR PDB; 1T83; X-ray; 3.00 A; C=19-194. DR PDB; 1T89; X-ray; 3.50 A; C=19-194. DR PDB; 6EAQ; X-ray; 2.22 A; C=19-193. DR PDBsum; 1E4J; -. DR PDBsum; 1E4K; -. DR PDBsum; 1FNL; -. DR PDBsum; 1T83; -. DR PDBsum; 1T89; -. DR PDBsum; 6EAQ; -. DR AlphaFoldDB; O75015; -. DR SMR; O75015; -. DR BioGRID; 108509; 49. DR IntAct; O75015; 1. DR STRING; 9606.ENSP00000433642; -. DR BindingDB; O75015; -. DR ChEMBL; CHEMBL5842; -. DR DrugBank; DB00092; Alefacept. DR DrugBank; DB00087; Alemtuzumab. DR DrugBank; DB06607; Catumaxomab. DR DrugBank; DB00002; Cetuximab. DR DrugBank; DB00111; Daclizumab. DR DrugBank; DB00005; Etanercept. DR DrugBank; DB00056; Gemtuzumab ozogamicin. DR DrugBank; DB00028; Human immunoglobulin G. DR DrugBank; DB00075; Muromonab. DR DrugBank; DB00108; Natalizumab. DR DrugBank; DB00110; Palivizumab. DR DrugBank; DB11767; Sarilumab. DR TCDB; 8.A.23.2.7; the basigin (basigin) family. DR GlyConnect; 1463; 2 N-Linked glycans (1 site). DR GlyConnect; 3001; 29 N-Linked glycans. DR GlyCosmos; O75015; 6 sites, 2 glycans. DR GlyGen; O75015; 6 sites, 2 N-linked glycans (1 site). DR iPTMnet; O75015; -. DR PhosphoSitePlus; O75015; -. DR BioMuta; FCGR3B; -. DR jPOST; O75015; -. DR MassIVE; O75015; -. DR PaxDb; 9606-ENSP00000433642; -. DR PeptideAtlas; O75015; -. DR ProteomicsDB; 49693; -. DR ABCD; O75015; 15 sequenced antibodies. DR Antibodypedia; 10871; 818 antibodies from 26 providers. DR DNASU; 2215; -. DR Ensembl; ENST00000367964.6; ENSP00000356941.2; ENSG00000162747.13. DR Ensembl; ENST00000650385.1; ENSP00000497461.1; ENSG00000162747.13. DR GeneID; 2215; -. DR KEGG; hsa:2215; -. DR MANE-Select; ENST00000650385.1; ENSP00000497461.1; NM_001244753.2; NP_001231682.2. DR UCSC; uc021pdo.2; human. DR AGR; HGNC:3620; -. DR CTD; 2215; -. DR DisGeNET; 2215; -. DR GeneCards; FCGR3B; -. DR HGNC; HGNC:3620; FCGR3B. DR HPA; ENSG00000162747; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; FCGR3B; -. DR MIM; 610665; gene. DR neXtProt; NX_O75015; -. DR OpenTargets; ENSG00000162747; -. DR Orphanet; 464370; Neonatal alloimmune neutropenia. DR Orphanet; 536; Systemic lupus erythematosus. DR PharmGKB; PA28066; -. DR VEuPathDB; HostDB:ENSG00000162747; -. DR eggNOG; ENOG502RU1M; Eukaryota. DR GeneTree; ENSGT01050000244808; -. DR HOGENOM; CLU_023383_1_0_1; -. DR InParanoid; O75015; -. DR OrthoDB; 5261894at2759; -. DR PhylomeDB; O75015; -. DR TreeFam; TF335097; -. DR PathwayCommons; O75015; -. DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; O75015; -. DR SIGNOR; O75015; -. DR BioGRID-ORCS; 2215; 8 hits in 1064 CRISPR screens. DR EvolutionaryTrace; O75015; -. DR GeneWiki; FCGR3B; -. DR GenomeRNAi; 2215; -. DR Pharos; O75015; Tbio. DR PRO; PR:O75015; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O75015; Protein. DR Bgee; ENSG00000162747; Expressed in blood and 146 other cell types or tissues. DR ExpressionAtlas; O75015; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome. DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW. DR GO; GO:0034235; F:GPI anchor binding; IDA:UniProtKB. DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central. DR CDD; cd05752; Ig1_FcgammaR_like; 1. DR CDD; cd05753; Ig2_FcgammaR_like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR PANTHER; PTHR11481; IMMUNOGLOBULIN FC RECEPTOR; 1. DR PANTHER; PTHR11481:SF97; LOW AFFINITY IMMUNOGLOBULIN GAMMA FC REGION RECEPTOR II-A-RELATED; 1. DR Pfam; PF13895; Ig_2; 2. DR SMART; SM00409; IG; 2. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 1. DR Genevisible; O75015; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; KW IgG-binding protein; Immunoglobulin domain; Lipoprotein; Membrane; KW Receptor; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT CHAIN 17..200 FT /note="Low affinity immunoglobulin gamma Fc region receptor FT III-B" FT /id="PRO_0000015151" FT PROPEP 201..233 FT /note="Removed in mature form" FT /evidence="ECO:0000255" FT /id="PRO_0000015152" FT DOMAIN 40..96 FT /note="Ig-like C2-type 1" FT DOMAIN 121..179 FT /note="Ig-like C2-type 2" FT LIPID 200 FT /note="GPI-anchor amidated serine" FT /evidence="ECO:0000255" FT CARBOHYD 56 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 82 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 92 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 180 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 187 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 47..89 FT /evidence="ECO:0000269|PubMed:10917521, FT ECO:0000269|PubMed:11021536, ECO:0007744|PDB:1FNL" FT DISULFID 128..172 FT /evidence="ECO:0000269|PubMed:10917521, FT ECO:0000269|PubMed:11021536, ECO:0007744|PDB:1FNL" FT VARIANT 36 FT /note="S -> R (in allele FCGR3B*01; dbSNP:rs200688856)" FT /id="VAR_003956" FT VARIANT 65 FT /note="N -> S (in allele FCGR3B*02 and allele FCGR3B*03; FT dbSNP:rs448740)" FT /evidence="ECO:0000269|PubMed:16710414" FT /id="VAR_003963" FT VARIANT 78 FT /note="A -> D (in allele FCGR3B*03; dbSNP:rs5030738)" FT /evidence="ECO:0000269|PubMed:9028335" FT /id="VAR_008802" FT VARIANT 82 FT /note="N -> D (in allele FCGR3B*01; dbSNP:rs147574249)" FT /id="VAR_003957" FT VARIANT 106 FT /note="I -> V (in allele FCGR3B*01; dbSNP:rs2290834)" FT /id="VAR_003964" FT MUTAGEN 203 FT /note="S->P: Abolishes membrane anchoring via FT glycosylphosphatidylinositol." FT /evidence="ECO:0000269|PubMed:1825220" FT MUTAGEN 203 FT /note="S->T,Y,A,D,K: Has no effect on membrane anchoring FT via glycosylphosphatidylinositol." FT /evidence="ECO:0000269|PubMed:1825220" FT STRAND 27..32 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 35..38 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 43..48 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 59..62 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 72..78 FT /evidence="ECO:0007829|PDB:1FNL" FT HELIX 81..83 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 85..90 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:1T89" FT STRAND 124..130 FT /evidence="ECO:0007829|PDB:1FNL" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:6EAQ" FT STRAND 137..143 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 157..161 FT /evidence="ECO:0007829|PDB:1FNL" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 168..176 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 179..182 FT /evidence="ECO:0007829|PDB:1FNL" FT STRAND 186..191 FT /evidence="ECO:0007829|PDB:1FNL" SQ SEQUENCE 233 AA; 26243 MW; 4EC0CDDE2ACF0CAC CRC64; MWQLLLPTAL LLLVSAGMRT EDLPKAVVFL EPQWYSVLEK DSVTLKCQGA YSPEDNSTQW FHNENLISSQ ASSYFIDAAT VNDSGEYRCQ TNLSTLSDPV QLEVHIGWLL LQAPRWVFKE EDPIHLRCHS WKNTALHKVT YLQNGKDRKY FHHNSDFHIP KATLKDSGSY FCRGLVGSKN VSSETVNITI TQGLAVSTIS SFSPPGYQVS FCLVMVLLFA VDTGLYFSVK TNI //