ID FCG2C_HUMAN Reviewed; 323 AA. AC P31995; O00523; O00524; O00525; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 02-SEP-2026, entry version 198. DE RecName: Full=Low affinity immunoglobulin gamma Fc region receptor II-c; DE Short=IgG Fc receptor II-c; DE AltName: Full=CDw32; DE AltName: Full=Fc-gamma RII-c; DE Short=Fc-gamma-RIIc; DE Short=FcRII-c; DE AltName: CD_antigen=CD32; DE Flags: Precursor; GN Name=FCGR2C; Synonyms=CD32, FCG2, IGFR2; 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] (ISOFORM IIC1). RC TISSUE=Placenta; RX PubMed=2531080; DOI=10.1002/j.1460-2075.1989.tb08540.x; RA Stuart S.G., Simister N.E., Clarkson S.B., Kacinski B.M., Shapiro M., RA Mellman I.; RT "Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in RT macrophages, lymphocytes and IgG-transporting placental epithelium."; RL EMBO J. 8:3657-3666(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS IIC1; IIC2; IIC3 AND IIC4). RC TISSUE=Natural killer cell; RX PubMed=9516136; DOI=10.1182/blood.v91.7.2369; RA Metes D., Ernst L.K., Chambers W.H., Sulica A., Herberman R.B., Morel P.A.; RT "Expression of functional CD32 molecules on human NK cells is determined by RT an allelic polymorphism of the FcgammaRIIC gene."; RL Blood 91:2369-2380(1998). RN [3] RP PHOSPHORYLATION AT TYR-294 AND TYR-310. RX PubMed=8756631; DOI=10.1128/mcb.16.9.4735; RA Bewarder N., Weinrich V., Budde P., Hartmann D., Flaswinkel H., Reth M., RA Frey J.; RT "In vivo and in vitro specificity of protein tyrosine kinases for RT immunoglobulin G receptor (FcgammaRII) phosphorylation."; RL Mol. Cell. Biol. 16:4735-4743(1996). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 45-217, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-187. RX PubMed=23744091; DOI=10.1093/protein/gzt022; RA Mimoto F., Katada H., Kadono S., Igawa T., Kuramochi T., Muraoka M., RA Wada Y., Haraya K., Miyazaki T., Hattori K.; RT "Engineered antibody Fc variant with selectively enhanced FcgammaRIIb RT binding over both FcgammaRIIa(R131) and FcgammaRIIa(H131)."; RL Protein Eng. Des. Sel. 26:589-598(2013). CC -!- FUNCTION: Receptor for the Fc region of complexed immunoglobulins CC gamma. Low affinity receptor. Involved in a variety of effector and CC regulatory functions such as phagocytosis of immune complexes and CC modulation of antibody production by B-cells. CC -!- INTERACTION: CC P31995; P02741: CRP; NbExp=2; IntAct=EBI-1396036, EBI-1395983; CC P31995; P16333: NCK1; NbExp=2; IntAct=EBI-1396036, EBI-389883; CC -!- SUBCELLULAR LOCATION: [Isoform IIC4]: Cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform IIC3]: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform IIC2]: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform IIC1]: Cell membrane; Single-pass type I CC membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=IIC1; Synonyms=C1; CC IsoId=P31995-1; Sequence=Displayed; CC Name=IIC2; CC IsoId=P31995-2; Sequence=VSP_002646; CC Name=IIC3; CC IsoId=P31995-3; Sequence=VSP_002645; CC Name=IIC4; CC IsoId=P31995-4; Sequence=VSP_002644; CC -!- TISSUE SPECIFICITY: Isoform IIC1 is detected in monocytes, macrophages, CC polymorphonuclear cells and natural killer cells. CC -!- DOMAIN: Contains an intracytoplasmic twice repeated motif referred as CC immunoreceptor tyrosine-based activator motif (ITAM). These motifs are CC involved in triggering cell activation upon receptors aggregation. CC -!- PTM: Phosphorylated by SRC-type Tyr-kinases such as LYN, BLK, FYN and CC SYK. {ECO:0000269|PubMed:8756631}. CC -!- CAUTION: Has sometimes been attributed to correspond to FcR-IIB. CC {ECO:0000305}. CC -!- CAUTION: FCGR2C is both a gene and a pseudogene in the human CC population, the reference genome corresponding currently to the non- CC functional allele with a stop codon at position 57. The sequence shown CC here with a Gln at that position is the one of the functional protein. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA35643.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; X17652; CAA35642.1; -; mRNA. DR EMBL; X17652; CAA35643.1; ALT_INIT; mRNA. DR EMBL; U90938; AAC12807.1; -; mRNA. DR EMBL; U90939; AAC12808.1; -; mRNA. DR EMBL; U90940; AAC12809.1; -; mRNA. DR EMBL; U90941; AAC12810.1; -; mRNA. DR PIR; S06946; S06946. DR RefSeq; NP_963857.3; NM_201563.5. DR PDB; 3WJL; X-ray; 2.86 A; C=45-217. DR PDB; 6YAX; X-ray; 2.80 A; AAA/BBB=43-217. DR AlphaFoldDB; P31995; -. DR SMR; P31995; -. DR BioGRID; 114556; 2. DR FunCoup; P31995; 216. DR IntAct; P31995; 8. DR NDEx; IQUERY-CP-FCGR2C; 1 NDEx IQuery Curated Pathway. DR DrugBank; DB00087; Alemtuzumab. DR DrugBank; DB00112; Bevacizumab. DR DrugBank; DB00111; Daclizumab. DR DrugBank; DB00005; Etanercept. DR DrugBank; DB00028; Human immunoglobulin G. DR GlyCosmos; P31995; 3 sites, No reported glycans. DR GlyGen; P31995; 5 sites. DR iPTMnet; P31995; -. DR PhosphoSitePlus; P31995; -. DR BioMuta; FCGR2C; -. DR DMDM; 399478; -. DR MassIVE; P31995; -. DR PeptideAtlas; P31995; -. DR ProteomicsDB; 54825; -. [P31995-1] DR ProteomicsDB; 54826; -. [P31995-2] DR ProteomicsDB; 54827; -. [P31995-3] DR ProteomicsDB; 54828; -. [P31995-4] DR Pumba; P31995; -. DR TopDownProteomics; P31995-4; -. [P31995-4] DR ABCD; P31995; 1 sequenced antibody. DR DNASU; 9103; -. DR GeneID; 9103; -. DR KEGG; hsa:9103; -. DR AGR; HGNC:15626; -. DR CTD; 9103; -. DR DisGeNET; 9103; -. DR GeneCards; FCGR2C; -. DR HGNC; HGNC:15626; FCGR2C. DR MalaCards; FCGR2C; -. DR MIM; 612169; gene. DR Orphanet; 3002; Immune thrombocytopenia. DR InParanoid; P31995; -. DR OrthoDB; 6151406at2759; -. DR PAN-GO; P31995; 7 GO annotations based on evolutionary models. DR PhylomeDB; P31995; -. DR PathwayCommons; P31995; -. DR SignaLink; P31995; -. DR SIGNOR; P31995; -. DR BioGRID-ORCS; 2213; 14 hits in 1145 CRISPR screens. DR BioGRID-ORCS; 9103; 1 hit in 128 CRISPR screens. DR EvolutionaryTrace; P31995; -. DR Pharos; P31995; Tdark. DR PRO; PR:P31995; -. DR Proteomes; UP000005640; Unplaced. DR RNAct; P31995; protein. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0019864; F:IgG binding; IBA:GO_Central. DR GO; GO:0019770; F:IgG receptor activity; IBA:GO_Central. DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB. DR GO; GO:0001788; P:antibody-dependent cellular cytotoxicity; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:0050766; P:positive regulation of phagocytosis; IBA:GO_Central. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IBA:GO_Central. DR CDD; cd05752; Ig1_FcgammaR_like; 1. DR CDD; cd05753; Ig2_FcgammaR_like; 1. DR FunFam; 2.60.40.10:FF:000217; High affinity immunoglobulin gamma Fc receptor I; 1. DR FunFam; 2.60.40.10:FF:000356; Low affinity immunoglobulin gamma Fc region receptor III-A; 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; IPR050488; Ig_Fc_receptor. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR PANTHER; PTHR11481; IMMUNOGLOBULIN FC RECEPTOR; 1. DR PANTHER; PTHR11481:SF97; LOW AFFINITY IMMUNOGLOBULIN GAMMA FC REGION RECEPTOR II-B-RELATED; 1. DR Pfam; PF13895; Ig_2; 2. DR SMART; SM00409; IG; 2. DR SMART; SM00408; IGc2; 2. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 2. DR PDBsum; 3WJL; -. DR PDBsum; 6YAX; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; KW Disulfide bond; Glycoprotein; IgG-binding protein; Immunoglobulin domain; KW Membrane; Phosphoprotein; Proteomics identification; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..42 FT /evidence="ECO:0000255" FT CHAIN 43..323 FT /note="Low affinity immunoglobulin gamma Fc region receptor FT II-c" FT /id="PRO_0000015148" FT TOPO_DOM 43..223 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 224..246 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 247..323 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 48..127 FT /note="Ig-like C2-type 1" FT DOMAIN 131..213 FT /note="Ig-like C2-type 2" FT REGION 277..323 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 294 FT /note="Phosphotyrosine; by SRC-type Tyr-kinases" FT /evidence="ECO:0000269|PubMed:8756631" FT MOD_RES 310 FT /note="Phosphotyrosine; by SRC-type Tyr-kinases" FT /evidence="ECO:0000269|PubMed:8756631" FT CARBOHYD 106 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:0000269|PubMed:23744091" FT DISULFID 71..113 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:23744091" FT DISULFID 152..196 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:23744091" FT VAR_SEQ 216..323 FT /note="APSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISANSTDPVKAAQFEP FT PGRQMIAIRKRQPEETNNDYETADGGYMTLNPRAPTDDDKNIYLTLPPNDHVNSNN -> FT GPRLRTAAKQSSLVGAEVP (in isoform IIC4)" FT /evidence="ECO:0000303|PubMed:9516136" FT /id="VSP_002644" FT VAR_SEQ 255..323 FT /note="NSTDPVKAAQFEPPGRQMIAIRKRQPEETNNDYETADGGYMTLNPRAPTDDD FT KNIYLTLPPNDHVNSNN -> TWTSNDCHQKETT (in isoform IIC3)" FT /evidence="ECO:0000303|PubMed:9516136" FT /id="VSP_002645" FT VAR_SEQ 267..323 FT /note="PPGRQMIAIRKRQPEETNNDYETADGGYMTLNPRAPTDDDKNIYLTLPPNDH FT VNSNN -> MLSCSHLDVK (in isoform IIC2)" FT /evidence="ECO:0000303|PubMed:9516136" FT /id="VSP_002646" FT CONFLICT 151 FT /note="R -> K (in Ref. 2; AAC12810)" FT /evidence="ECO:0000305" FT CONFLICT 164 FT /note="T -> I (in Ref. 2; AAC12809)" FT /evidence="ECO:0000305" FT STRAND 52..56 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 59..62 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 66..71 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 83..86 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:3WJL" FT STRAND 96..102 FT /evidence="ECO:0007829|PDB:6YAX" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 109..114 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:6YAX" FT HELIX 120..123 FT /evidence="ECO:0007829|PDB:3WJL" FT STRAND 124..129 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 140..143 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 148..154 FT /evidence="ECO:0007829|PDB:6YAX" FT HELIX 155..157 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 160..177 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 180..185 FT /evidence="ECO:0007829|PDB:6YAX" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 192..200 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:6YAX" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:6YAX" FT STRAND 210..215 FT /evidence="ECO:0007829|PDB:6YAX" SQ SEQUENCE 323 AA; 35578 MW; DC4C1A22A0DE4572 CRC64; 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 RISANSTDPV KAAQFEPPGR QMIAIRKRQP EETNNDYETA DGGYMTLNPR APTDDDKNIY LTLPPNDHVN SNN //