FCG2C_HUMAN
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 25-MAY-2022, entry version 183.
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;
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};
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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 RefSeq; XP_011507594.1; XM_011509292.2.
DR PDB; 3WJL; X-ray; 2.86 A; C=45-217.
DR PDB; 6YAX; X-ray; 2.80 A; AAA/BBB=43-217.
DR PDBsum; 3WJL; -.
DR PDBsum; 6YAX; -.
DR AlphaFoldDB; P31995; -.
DR SMR; P31995; -.
DR BioGRID; 114556; 2.
DR IntAct; P31995; 8.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00028; Human immunoglobulin G.
DR GlyGen; P31995; 4 sites.
DR iPTMnet; P31995; -.
DR PhosphoSitePlus; P31995; -.
DR BioMuta; FCGR2C; -.
DR DMDM; 399478; -.
DR jPOST; P31995; -.
DR MassIVE; P31995; -.
DR MaxQB; P31995; -.
DR PeptideAtlas; P31995; -.
DR PRIDE; P31995; -.
DR ProteomicsDB; 54825; -. [P31995-1]
DR ProteomicsDB; 54826; -. [P31995-2]
DR ProteomicsDB; 54827; -. [P31995-3]
DR ProteomicsDB; 54828; -. [P31995-4]
DR TopDownProteomics; P31995-4; -. [P31995-4]
DR DNASU; 9103; -.
DR GeneID; 9103; -.
DR KEGG; hsa:9103; -.
DR CTD; 9103; -.
DR DisGeNET; 9103; -.
DR GeneCards; FCGR2C; -.
DR HGNC; HGNC:15626; FCGR2C.
DR MalaCards; FCGR2C; -.
DR MIM; 612169; gene.
DR neXtProt; NX_P31995; -.
DR Orphanet; 3002; Immune thrombocytopenia.
DR InParanoid; P31995; -.
DR PhylomeDB; P31995; -.
DR PathwayCommons; P31995; -.
DR SignaLink; P31995; -.
DR SIGNOR; P31995; -.
DR BioGRID-ORCS; 2213; 13 hits in 1062 CRISPR screens.
DR BioGRID-ORCS; 9103; 1 hit in 109 CRISPR screens.
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:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; NAS:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 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 InterPro; IPR003598; Ig_sub2.
DR Pfam; PF13895; Ig_2; 2.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
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; Receptor; Reference proteome; Repeat; Signal;
KW 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 51..53
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:3WJL"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:3WJL"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 170..177
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:3WJL"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 192..200
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:3WJL"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:3WJL"
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
