FCRL3_HUMAN
ID FCRL3_HUMAN Reviewed; 734 AA.
AC Q96P31; A0N0M4; A8MTH7; D3DVD2; Q5VXZ8; Q8N6S2; Q96LA4; Q96P27; Q96P28;
AC Q96P29; Q96P30;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Fc receptor-like protein 3 {ECO:0000305};
DE Short=FcR-like protein 3 {ECO:0000305};
DE Short=FcRL3 {ECO:0000305};
DE AltName: Full=Fc receptor homolog 3 {ECO:0000305};
DE Short=FcRH3 {ECO:0000305};
DE AltName: Full=IFGP family protein 3;
DE Short=hIFGP3;
DE AltName: Full=Immune receptor translocation-associated protein 3;
DE AltName: Full=SH2 domain-containing phosphatase anchor protein 2;
DE AltName: CD_antigen=CD307c;
DE Flags: Precursor;
GN Name=FCRL3 {ECO:0000312|HGNC:HGNC:18506};
GN Synonyms=FCRH3 {ECO:0000312|HGNC:HGNC:18506},
GN IFGP3 {ECO:0000312|HGNC:HGNC:18506}, IRTA3 {ECO:0000312|HGNC:HGNC:18506},
GN SPAP2 {ECO:0000312|HGNC:HGNC:18506};
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 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lymph node;
RX PubMed=11493702; DOI=10.1073/pnas.171308498;
RA Davis R.S., Wang Y.-H., Kubagawa H., Cooper M.D.;
RT "Identification of a family of Fc receptor homologs with preferential B
RT cell expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9772-9777(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), PHOSPHORYLATION,
RP INTERACTION WITH PTPN6; PTPN11; SYK AND ZAP70, MUTAGENESIS OF TYR-650;
RP TYR-662; TYR-692 AND TYR-722, AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow;
RX PubMed=12051764; DOI=10.1016/s0006-291x(02)00332-7;
RA Xu M.-J., Zhao R., Cao H., Zhao Z.J.;
RT "SPAP2, an Ig family receptor containing both ITIMs and ITAMs.";
RL Biochem. Biophys. Res. Commun. 293:1037-1046(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ASP-28.
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-28.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CHARACTERIZATION, AND TISSUE SPECIFICITY.
RX PubMed=11929751; DOI=10.1182/blood.v99.8.2662;
RA Miller I., Hatzivassiliou G., Cattoretti G., Mendelsohn C.,
RA Dalla-Favera R.;
RT "IRTAs: a new family of immunoglobulin-like receptors differentially
RT expressed in B cells.";
RL Blood 99:2662-2669(2002).
RN [9]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS AND GRAVES DISEASE, AND TISSUE
RP SPECIFICITY.
RX PubMed=15838509; DOI=10.1038/ng1540;
RA Kochi Y., Yamada R., Suzuki A., Harley J.B., Shirasawa S., Sawada T.,
RA Bae S.-C., Tokuhiro S., Chang X., Sekine A., Takahashi A., Tsunoda T.,
RA Ohnishi Y., Kaufman K.M., Kang C.P., Kang C., Otsubo S., Yumura W.,
RA Mimori A., Koike T., Nakamura Y., Sasazuki T., Yamamoto K.;
RT "A functional variant in FCRL3, encoding Fc receptor-like 3, is associated
RT with rheumatoid arthritis and several autoimmunities.";
RL Nat. Genet. 37:478-485(2005).
RN [10]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=16176992; DOI=10.1136/ard.2005.043489;
RA Ikari K., Momohara S., Nakamura T., Hara M., Yamanaka H., Tomatsu T.,
RA Kamatani N.;
RT "Supportive evidence for a genetic association of the FCRL3 promoter
RT polymorphism with rheumatoid arthritis.";
RL Ann. Rheum. Dis. 65:671-673(2006).
RN [11]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=16476711; DOI=10.1136/ard.2005.048454;
RA Martinez A., Sanchez E., Valdivia A., Orozco G., Lopez-Nevot M.A.,
RA Pascual-Salcedo D., Balsa A., Fernandez-Gutierrez B., de la Concha E.G.,
RA Garcia-Sanchez A., Koeleman B.P.C., Urcelay E., Martin J.;
RT "Epistatic interaction between FCRL3 and NFkappaB1 genes in Spanish
RT patients with rheumatoid arthritis.";
RL Ann. Rheum. Dis. 65:1188-1191(2006).
RN [12]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=16859508; DOI=10.1186/ar2006;
RA Eyre S., Bowes J., Potter C., Worthington J., Barton A.;
RT "Association of the FCRL3 gene with rheumatoid arthritis: a further example
RT of population specificity?";
RL Arthritis Res. Ther. 8:R117-R117(2006).
RN [13]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=17133579; DOI=10.1002/art.22270;
RA Newman W.G., Zhang Q., Liu X., Walker E., Ternan H., Owen J., Johnson B.,
RA Greer W., Mosher D.P., Maksymowych W.P., Bykerk V.P., Keystone E.C.,
RA Amos C.I., Siminovitch K.A.;
RT "Rheumatoid arthritis association with the FCRL3 -169C polymorphism is
RT restricted to PTPN22 1858T-homozygous individuals in a Canadian
RT population.";
RL Arthritis Rheum. 54:3820-3827(2006).
RN [14]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16849395; DOI=10.1093/intimm/dxl069;
RA Polson A.G., Zheng B., Elkins K., Chang W., Du C., Dowd P., Yen L., Tan C.,
RA Hongo J.-A., Koeppen H., Ebens A.;
RT "Expression pattern of the human FcRH/IRTA receptors in normal tissue and
RT in B-chronic lymphocytic leukemia.";
RL Int. Immunol. 18:1363-1373(2006).
RN [15]
RP INVOLVEMENT IN GRAVES DISEASE.
RX PubMed=16384851; DOI=10.1210/jc.2005-1634;
RA Simmonds M.J., Heward J.M., Carr-Smith J., Foxall H., Franklyn J.A.,
RA Gough S.C.L.;
RT "Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2
RT to the pathogenesis of Graves' disease.";
RL J. Clin. Endocrinol. Metab. 91:1056-1061(2006).
RN [16]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=17179172; DOI=10.1136/ard.2006.064949;
RA Thabet M.M., Wesoly J., Slagboom P.E., Toes R.E.M., Huizinga T.W.J.;
RT "FCRL3 promoter 169 CC homozygosity is associated with susceptibility to
RT rheumatoid arthritis in Dutch Caucasians.";
RL Ann. Rheum. Dis. 66:803-806(2007).
RN [17]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=17763442; DOI=10.1002/art.22857;
RA Begovich A.B., Chang M., Schrodi S.J.;
RT "Meta-analysis evidence of a differential risk of the FCRL3 -169T-->C
RT polymorphism in white and East Asian rheumatoid arthritis patients.";
RL Arthritis Rheum. 56:3168-3171(2007).
RN [18]
RP INVOLVEMENT IN GRAVES DISEASE.
RX PubMed=17952073; DOI=10.1038/ng.2007.17;
RG The Wellcome Trust case control consortium;
RG The Australo-Anglo-American spondylitis consortium;
RT "Association scan of 14,500 nonsynonymous SNPs in four diseases identifies
RT autoimmunity variants.";
RL Nat. Genet. 39:1329-1337(2007).
RN [19]
RP FUNCTION, INTERACTION WITH INPP5D; PTPN6; PTPN11; SYK AND ZAP70,
RP PHOSPHORYLATION AT TYR-650; TYR-662; TYR-692 AND TYR-722, AND MUTAGENESIS
RP OF TYR-650; TYR-662; TYR-692 AND TYR-722.
RX PubMed=19843936; DOI=10.4049/jimmunol.0901982;
RA Kochi Y., Myouzen K., Yamada R., Suzuki A., Kurosaki T., Nakamura Y.,
RA Yamamoto K.;
RT "FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-
RT cell receptor-mediated signaling.";
RL J. Immunol. 183:5502-5510(2009).
RN [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19494275; DOI=10.4049/jimmunol.0802230;
RA Nagata S., Ise T., Pastan I.;
RT "Fc receptor-like 3 protein expressed on IL-2 nonresponsive subset of human
RT regulatory T cells.";
RL J. Immunol. 182:7518-7526(2009).
RN [21]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20190142; DOI=10.4049/jimmunol.0903943;
RA Swainson L.A., Mold J.E., Bajpai U.D., McCune J.M.;
RT "Expression of the autoimmune susceptibility gene FcRL3 on human regulatory
RT T cells is associated with dysfunction and high levels of programmed cell
RT death-1.";
RL J. Immunol. 184:3639-3647(2010).
RN [22]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=22392608; DOI=10.1002/art.34457;
RA Bajpai U.D., Swainson L.A., Mold J.E., Graf J.D., Imboden J.B.,
RA McCune J.M.;
RT "A functional variant in FCRL3 is associated with higher Fc receptor-like 3
RT expression on T cell subsets and rheumatoid arthritis disease activity.";
RL Arthritis Rheum. 64:2451-2459(2012).
RN [23]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=23857366; DOI=10.1002/eji.201243068;
RA Li F.J., Schreeder D.M., Li R., Wu J., Davis R.S.;
RT "FCRL3 promotes TLR9-induced B-cell activation and suppresses plasma cell
RT differentiation.";
RL Eur. J. Immunol. 43:2980-2992(2013).
RN [24]
RP INVOLVEMENT IN GRAVES DISEASE.
RX PubMed=26629249;
RA Wu S., Cai T., Chen F., He X., Cui Z.;
RT "Genetic associations of FCRL3 polymorphisms with the susceptibility of
RT Graves ophthalmopathy in a Chinese population.";
RL Int. J. Clin. Exp. Med. 8:16948-16954(2015).
RN [25]
RP INVOLVEMENT IN RHEUMATOID ARTHRITIS.
RX PubMed=26746625; DOI=10.1016/j.humimm.2015.12.007;
RA Lin X., Zhang Y., Chen Q.;
RT "FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis.";
RL Hum. Immunol. 77:223-229(2016).
RN [26]
RP INVOLVEMENT IN MULTIPLE SCLEROSIS.
RX PubMed=25862376; DOI=10.1007/s12035-015-9149-7;
RA Yuan M., Wei L., Zhou R., Bai Q., Wei Y., Zhang W., Huang Y.;
RT "Four FCRL3 Gene Polymorphisms (FCRL3_3, _5, _6, _8) Confer Susceptibility
RT to Multiple Sclerosis: Results from a Case-Control Study.";
RL Mol. Neurobiol. 53:2029-2035(2016).
RN [27]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-445.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Promotes TLR9-induced B-cell proliferation, activation and
CC survival but inhibits antibody production and suppresses plasma cell
CC differentiation. Enhances activation of NF-kappa-B and MAPK signaling
CC pathways in TLR9 stimulated B-cells (PubMed:23857366). Has inhibitory
CC potentional on B-cell receptor (BCR)-mediated signaling, possibly
CC through association with SH2 domain-containing phosphatases. Inhibits
CC cell tyrosine phosphorylation, calcium mobilization and activation-
CC induced cell death induced through BCR signaling (PubMed:19843936).
CC Regulatory T-cells expressing FCRL3 exhibit a memory phenotype, are
CC relatively nonresponsive to antigenic stimulation in presence of IL2
CC and have reduced capacity to suppress the proliferation of effector T-
CC cells (PubMed:20190142, PubMed:19494275). {ECO:0000269|PubMed:19494275,
CC ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:20190142,
CC ECO:0000269|PubMed:23857366}.
CC -!- SUBUNIT: Interacts (via phosphorylated ITIM motifs) with phosphatases
CC INPP5D, PTPN6 and PTPN11. Interacts (via ITIM motifs) SYK and ZAP70.
CC {ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:19843936}.
CC -!- INTERACTION:
CC Q96P31-6; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-17443171, EBI-1754287;
CC Q96P31-6; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-17443171, EBI-11522780;
CC Q96P31-6; P24593: IGFBP5; NbExp=3; IntAct=EBI-17443171, EBI-720480;
CC Q96P31-6; P11836: MS4A1; NbExp=3; IntAct=EBI-17443171, EBI-2808234;
CC Q96P31-6; P22732: SLC2A5; NbExp=3; IntAct=EBI-17443171, EBI-2825135;
CC Q96P31-6; Q99726: SLC30A3; NbExp=3; IntAct=EBI-17443171, EBI-10294651;
CC Q96P31-6; P02808: STATH; NbExp=3; IntAct=EBI-17443171, EBI-738687;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16849395,
CC ECO:0000269|PubMed:20190142}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:16849395}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=Spap2a;
CC IsoId=Q96P31-1; Sequence=Displayed;
CC Name=2; Synonyms=Spap2b;
CC IsoId=Q96P31-2; Sequence=VSP_033300;
CC Name=3; Synonyms=Spap2c;
CC IsoId=Q96P31-3; Sequence=VSP_033305;
CC Name=4; Synonyms=Spap2d;
CC IsoId=Q96P31-4; Sequence=VSP_033301, VSP_033303;
CC Name=5;
CC IsoId=Q96P31-5; Sequence=VSP_033302, VSP_033304;
CC Name=6;
CC IsoId=Q96P31-6; Sequence=VSP_033308;
CC Name=7;
CC IsoId=Q96P31-7; Sequence=VSP_033306, VSP_033307;
CC -!- TISSUE SPECIFICITY: Primarily expressed in secondary lymphoid tissues
CC by mature subsets of B-cells. Low expression on transitional B cells
CC which increases to higher surface expression on mature and memory B-
CC cells with innate-like features (at protein level) (PubMed:23857366).
CC Expressed a low levels in naive and germinal center B-cells but also
CC expressed in NK cells (at protein level). Expressed in a population of
CC thymically derived natrurally ocurring regulatory T-cells that exhibits
CC a memory phenotype, specialized in suppressing immune response to self-
CC antigens (PubMed:20190142). Detected in spleen, lymph node, peripheral
CC blood lymphocytes, thymus, bone marrow, kidney, salivary gland, adrenal
CC gland and uterus. {ECO:0000269|PubMed:11493702,
CC ECO:0000269|PubMed:11929751, ECO:0000269|PubMed:12051764,
CC ECO:0000269|PubMed:15838509, ECO:0000269|PubMed:16849395,
CC ECO:0000269|PubMed:20190142, ECO:0000269|PubMed:23857366}.
CC -!- DEVELOPMENTAL STAGE: In B-cells, expression increases as a function of
CC differentiation and peaks on memory B-cells.
CC {ECO:0000269|PubMed:23857366}.
CC -!- PTM: Phosphorylated on cytoplasmic tyrosines; required for interaction
CC with protein tyrosine phosphatases and protein tyrosine kinases.
CC {ECO:0000269|PubMed:12051764}.
CC -!- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory
CC disease with autoimmune features and a complex genetic component. It
CC primarily affects the joints and is characterized by inflammatory
CC changes in the synovial membranes and articular structures, widespread
CC fibrinoid degeneration of the collagen fibers in mesenchymal tissues,
CC and by atrophy and rarefaction of bony structures.
CC {ECO:0000269|PubMed:15838509, ECO:0000269|PubMed:16176992,
CC ECO:0000269|PubMed:16476711, ECO:0000269|PubMed:16859508,
CC ECO:0000269|PubMed:17133579, ECO:0000269|PubMed:17179172,
CC ECO:0000269|PubMed:17763442, ECO:0000269|PubMed:22392608,
CC ECO:0000269|PubMed:26746625}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Genetic variation in FCRL3 may influence susceptibility
CC to autoimmune disorders, including Graves disease or multiple
CC sclerosis. Graves disease is an autoimmune disorder associated with
CC overactivity of the thyroid gland and hyperthyroidism. Multiple
CC sclerosis is an autoimmune/inflammatory neurodegenerative disease which
CC mainly affects young adults and is characterized by destruction of
CC myelin in the central nervous system. {ECO:0000269|PubMed:15838509,
CC ECO:0000269|PubMed:16384851, ECO:0000269|PubMed:17952073,
CC ECO:0000269|PubMed:25862376, ECO:0000269|PubMed:26629249}.
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; AY043466; AAK91779.1; -; mRNA.
DR EMBL; AF416901; AAL13290.1; -; mRNA.
DR EMBL; AF416902; AAL13291.1; -; mRNA.
DR EMBL; AF416903; AAL13292.1; -; mRNA.
DR EMBL; AF416904; AAL13293.1; -; mRNA.
DR EMBL; AF416905; AAL13294.1; -; mRNA.
DR EMBL; EF064732; ABK41915.1; -; Genomic_DNA.
DR EMBL; AK098122; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL356276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52872.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52876.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52877.1; -; Genomic_DNA.
DR EMBL; BC028933; AAH28933.1; -; mRNA.
DR CCDS; CCDS1167.1; -. [Q96P31-1]
DR CCDS; CCDS81385.1; -. [Q96P31-6]
DR RefSeq; NP_001307262.1; NM_001320333.1. [Q96P31-6]
DR RefSeq; NP_443171.2; NM_052939.3. [Q96P31-1]
DR RefSeq; XP_006711208.1; XM_006711145.1. [Q96P31-1]
DR AlphaFoldDB; Q96P31; -.
DR BioGRID; 125428; 43.
DR IntAct; Q96P31; 8.
DR STRING; 9606.ENSP00000357167; -.
DR GlyGen; Q96P31; 1 site.
DR iPTMnet; Q96P31; -.
DR PhosphoSitePlus; Q96P31; -.
DR BioMuta; FCRL3; -.
DR DMDM; 74761021; -.
DR MassIVE; Q96P31; -.
DR PaxDb; Q96P31; -.
DR PeptideAtlas; Q96P31; -.
DR PRIDE; Q96P31; -.
DR ProteomicsDB; 77608; -. [Q96P31-1]
DR ProteomicsDB; 77609; -. [Q96P31-2]
DR ProteomicsDB; 77610; -. [Q96P31-3]
DR ProteomicsDB; 77611; -. [Q96P31-4]
DR ProteomicsDB; 77612; -. [Q96P31-5]
DR ProteomicsDB; 77613; -. [Q96P31-6]
DR ProteomicsDB; 77614; -. [Q96P31-7]
DR Antibodypedia; 2552; 168 antibodies from 24 providers.
DR DNASU; 115352; -.
DR Ensembl; ENST00000368184.8; ENSP00000357167.3; ENSG00000160856.21. [Q96P31-1]
DR Ensembl; ENST00000368186.9; ENSP00000357169.5; ENSG00000160856.21. [Q96P31-6]
DR Ensembl; ENST00000477837.5; ENSP00000433430.1; ENSG00000160856.21. [Q96P31-2]
DR Ensembl; ENST00000485028.5; ENSP00000434331.1; ENSG00000160856.21. [Q96P31-1]
DR Ensembl; ENST00000492769.5; ENSP00000435487.1; ENSG00000160856.21. [Q96P31-3]
DR GeneID; 115352; -.
DR KEGG; hsa:115352; -.
DR MANE-Select; ENST00000368184.8; ENSP00000357167.3; NM_052939.4; NP_443171.2.
DR UCSC; uc001fqz.5; human. [Q96P31-1]
DR CTD; 115352; -.
DR DisGeNET; 115352; -.
DR GeneCards; FCRL3; -.
DR HGNC; HGNC:18506; FCRL3.
DR HPA; ENSG00000160856; Tissue enriched (lymphoid).
DR MIM; 180300; phenotype.
DR MIM; 606510; gene.
DR neXtProt; NX_Q96P31; -.
DR OpenTargets; ENSG00000160856; -.
DR PharmGKB; PA142671767; -.
DR VEuPathDB; HostDB:ENSG00000160856; -.
DR eggNOG; ENOG502S65W; Eukaryota.
DR GeneTree; ENSGT01050000244808; -.
DR HOGENOM; CLU_023383_6_1_1; -.
DR InParanoid; Q96P31; -.
DR OMA; VYSQIWS; -.
DR OrthoDB; 53940at2759; -.
DR PhylomeDB; Q96P31; -.
DR TreeFam; TF351107; -.
DR PathwayCommons; Q96P31; -.
DR SignaLink; Q96P31; -.
DR BioGRID-ORCS; 115352; 6 hits in 1058 CRISPR screens.
DR GeneWiki; FCRL3; -.
DR GenomeRNAi; 115352; -.
DR Pharos; Q96P31; Tbio.
DR PRO; PR:Q96P31; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96P31; protein.
DR Bgee; ENSG00000160856; Expressed in ileal mucosa and 121 other tissues.
DR ExpressionAtlas; Q96P31; baseline and differential.
DR Genevisible; Q96P31; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB.
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:0050859; P:negative regulation of B cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0002638; P:negative regulation of immunoglobulin production; IDA:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:1905184; P:positive regulation of protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0050864; P:regulation of B cell activation; IDA:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; IDA:UniProtKB.
DR GO; GO:0090279; P:regulation of calcium ion import; IDA:UniProtKB.
DR GO; GO:0034163; P:regulation of toll-like receptor 9 signaling pathway; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 6.
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 InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 4.
DR SMART; SM00409; IG; 6.
DR SMART; SM00408; IGc2; 5.
DR SUPFAM; SSF48726; SSF48726; 6.
DR PROSITE; PS50835; IG_LIKE; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..734
FT /note="Fc receptor-like protein 3"
FT /id="PRO_0000331640"
FT TOPO_DOM 18..573
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 574..594
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 595..734
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..98
FT /note="Ig-like C2-type 1"
FT DOMAIN 99..182
FT /note="Ig-like C2-type 2"
FT DOMAIN 192..270
FT /note="Ig-like C2-type 3"
FT DOMAIN 284..369
FT /note="Ig-like C2-type 4"
FT DOMAIN 383..470
FT /note="Ig-like C2-type 5"
FT DOMAIN 476..563
FT /note="Ig-like C2-type 6"
FT REGION 603..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 695..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 648..653
FT /note="ITIM motif 1"
FT MOTIF 660..665
FT /note="ITIM motif 2"
FT MOTIF 690..695
FT /note="ITIM motif 3"
FT MOTIF 720..725
FT /note="ITIM motif 4"
FT COMPBIAS 606..631
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..724
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 650
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:19843936"
FT MOD_RES 662
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:19843936"
FT MOD_RES 692
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:19843936"
FT MOD_RES 722
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:19843936"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 120..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 211..260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 309..358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 404..451
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 497..544
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 187..282
FT /note="ELFLHPVLRASSSTPIEGSPMTLTCETQLSPQRPDVQLQFSLFRDSQTLGLG
FT WSRSPRLQIPAMWTEDSGSYWCEVETVTHSIKKRSLRSQIRVQR -> G (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033300"
FT VAR_SEQ 187..189
FT /note="ELF -> GNG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033301"
FT VAR_SEQ 188..199
FT /note="LFLHPVLRASSS -> ARCPAAILPLQR (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033302"
FT VAR_SEQ 190..734
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033303"
FT VAR_SEQ 200..734
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033304"
FT VAR_SEQ 378
FT /note="I -> TLLSPSV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12051764"
FT /id="VSP_033305"
FT VAR_SEQ 698..707
FT /note="THPDDSAGEA -> EQSSRFSMSL (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033306"
FT VAR_SEQ 708..734
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033307"
FT VAR_SEQ 725..734
FT /note="VPRVLLASDH -> ILNPRKNKVQDFPCLCNT (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033308"
FT VARIANT 28
FT /note="N -> D (in dbSNP:rs7522061)"
FT /evidence="ECO:0000269|Ref.3, ECO:0000269|Ref.6"
FT /id="VAR_042924"
FT VARIANT 307
FT /note="L -> F (in dbSNP:rs12041673)"
FT /id="VAR_042925"
FT VARIANT 445
FT /note="H -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_042926"
FT VARIANT 660
FT /note="P -> L (in dbSNP:rs944627)"
FT /id="VAR_042927"
FT VARIANT 721
FT /note="N -> S (in dbSNP:rs2282284)"
FT /id="VAR_042928"
FT MUTAGEN 650
FT /note="Y->F: No effect on inhibition of cell death. No
FT effect on interaction with INPP5D, PTPN6 and PTPN11. Loss
FT of phosphorylation, calcium influx inhibition and
FT interaction with INPP5D, PTPN6 and PTPN11; when associated
FT with F-662; F-692 and F-722. Alters binding with SYK and
FT ZAP70; when associated with F-662. Decreases calcium influx
FT inhibition; when associated with F-662 and F-722. Decreases
FT calcium influx inhibition; when associated with F-692 and
FT F-722."
FT /evidence="ECO:0000269|PubMed:12051764,
FT ECO:0000269|PubMed:19843936"
FT MUTAGEN 662
FT /note="Y->F: Reduces inhibition of cell death. Decreases
FT interaction with INPP5D and PTPN6. No effect on interaction
FT with PTPN11. Loss of phosphorylation, calcium influx
FT inhibition and interaction with INPP5D, PTPN6 and PTPN11;
FT when associated with F-650; F-692 and F-722. Alters binding
FT with SYK and ZAP70; when associated with F-650. Decreases
FT calcium influx inhibition; when associated with F-650 and
FT F-722. Increases calcium influx inhibition; when associated
FT with F-650 and F-722."
FT /evidence="ECO:0000269|PubMed:12051764,
FT ECO:0000269|PubMed:19843936"
FT MUTAGEN 692
FT /note="Y->F: Partially reduces inhibition of cell death.
FT Decreases interaction with INPP5D and PTPN11. No effect on
FT interaction with PTPN6. Loss of phosphorylation, calcium
FT influx inhibition and interaction with INPP5D, PTPN6 and
FT PTPN11; when associated with F-650; F-662 and F-722. Alters
FT binding with PTPN6 and PTPN11; when associated with F-772.
FT Decreases calcium influx inhibition; when associated with
FT F-650 and F-722. Increases calcium influx inhibition; when
FT associated with F-650 and F-662. Decreases calcium influx
FT inhibition; when associated with F-722."
FT /evidence="ECO:0000269|PubMed:12051764,
FT ECO:0000269|PubMed:19843936"
FT MUTAGEN 722
FT /note="Y->F: No effect on inhibition of cell death. No
FT effect on interaction with INPP5D, PTPN6 and PTPN11. Loss
FT of phosphorylation, calcium influx inhibition and
FT interaction with INPP5D, PTPN6 and PTPN11; when associated
FT with F-650; F-662 and F-692. Alters binding with PTPN6 and
FT PTPN11; when associated with F-692. Decreases calcium
FT influx inhibition; when associated with F-650 and F-662.
FT Decreases calcium influx inhibition; when associated with
FT F-650 and F-692. Decreases calcium influx inhibition; when
FT associated with F-692."
FT /evidence="ECO:0000269|PubMed:12051764,
FT ECO:0000269|PubMed:19843936"
FT CONFLICT 244
FT /note="R -> K (in Ref. 4; AK098122)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="V -> A (in Ref. 1; AAK91779)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 734 AA; 80856 MW; B3411B73A35EC668 CRC64;
MLLWLLLLIL TPGREQSGVA PKAVLLLNPP WSTAFKGEKV ALICSSISHS LAQGDTYWYH
DEKLLKIKHD KIQITEPGNY QCKTRGSSLS DAVHVEFSPD WLILQALHPV FEGDNVILRC
QGKDNKNTHQ KVYYKDGKQL PNSYNLEKIT VNSVSRDNSK YHCTAYRKFY ILDIEVTSKP
LNIQVQELFL HPVLRASSST PIEGSPMTLT CETQLSPQRP DVQLQFSLFR DSQTLGLGWS
RSPRLQIPAM WTEDSGSYWC EVETVTHSIK KRSLRSQIRV QRVPVSNVNL EIRPTGGQLI
EGENMVLICS VAQGSGTVTF SWHKEGRVRS LGRKTQRSLL AELHVLTVKE SDAGRYYCAA
DNVHSPILST WIRVTVRIPV SHPVLTFRAP RAHTVVGDLL ELHCESLRGS PPILYRFYHE
DVTLGNSSAP SGGGASFNLS LTAEHSGNYS CDADNGLGAQ HSHGVSLRVT VPVSRPVLTL
RAPGAQAVVG DLLELHCESL RGSFPILYWF YHEDDTLGNI SAHSGGGASF NLSLTTEHSG
NYSCEADNGL GAQHSKVVTL NVTGTSRNRT GLTAAGITGL VLSILVLAAA AALLHYARAR
RKPGGLSATG TSSHSPSECQ EPSSSRPSRI DPQEPTHSKP LAPMELEPMY SNVNPGDSNP
IYSQIWSIQH TKENSANCPM MHQEHEELTV LYSELKKTHP DDSAGEASSR GRAHEEDDEE
NYENVPRVLL ASDH
