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 27-MAR-2024, entry version 174. 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=MAIA {ECO:0000303|PubMed:36070373}; 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}, IFGP3 GN {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 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] RP FUNCTION, INTERACTION WITH IZUMO1R/JUNO AND IZUMO1, SUBCELLULAR LOCATION, RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=36070373; DOI=10.1126/sciadv.abn0047; RA Vondrakova J., Frolikova M., Ded L., Cerny J., Postlerova P., RA Palenikova V., Simonik O., Nahacka Z., Basus K., Valaskova E., Machan R., RA Pacey A., Holubcova Z., Koubek P., Ezrova Z., Park S., Liu R., Partha R., RA Clark N., Neuzil J., Ikawa M., Erickson K., Lam K.S., Moore H., RA Komrskova K.; RT "MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human RT fertilization."; RL Sci. Adv. 8:eabn0047-eabn0047(2022). RN [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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). Acts as a human-specific CC epitope on the cell surface of oocytes (oolemma) and plays a role CC during sperm-egg adhesion and fusion (PubMed:36070373). Interacts with CC the IZUMO1-IZUMO1R/JUNO sperm-egg complex and replaces IZUMO1R/JUNO as CC IZUMO1 receptor during fertilization, thereby permitting species- CC specific gamete fusion (PubMed:36070373). {ECO:0000269|PubMed:19494275, CC ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:20190142, CC ECO:0000269|PubMed:23857366, ECO:0000269|PubMed:36070373}. CC -!- SUBUNIT: Interacts (via phosphorylated ITIM motifs) with phosphatases CC INPP5D, PTPN6 and PTPN11. Interacts (via ITIM motifs) SYK and ZAP70. CC Interacts with IZUMO1R/JUNO (PubMed:36070373). Interacts (via CC extracellular domain) with IZUMO1; the interaction replaces CC IZUMO1R/JUNO as IZUMO1 receptor after adhesion between sperm and egg CC (PubMed:36070373). {ECO:0000269|PubMed:12051764, CC ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:36070373}. 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, ECO:0000269|PubMed:36070373}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:16849395}. Cell projection, CC microvillus membrane {ECO:0000269|PubMed:36070373}. Note=Localized CC along the oolemma microvilli of unfertilized oocytes. CC {ECO:0000269|PubMed:36070373}. 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) (PubMed:20190142). Expressed CC in unfertilized oocytes (at protein level) (PubMed:36070373). Expressed CC in a population of thymically derived naturally occurring regulatory T- CC cells that exhibits a memory phenotype, specialized in suppressing CC immune response to self-antigens (PubMed:20190142). Detected in spleen, CC lymph node, peripheral blood lymphocytes, thymus, bone marrow, kidney, CC salivary gland, adrenal 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 ECO:0000269|PubMed:36070373}. CC -!- DEVELOPMENTAL STAGE: Expressed in mature metaphase II (MII) stage CC oocytes (at protein level) (PubMed:36070373). In B-cells, expression CC increases as a function of differentiation and peaks on memory B-cells. CC {ECO:0000269|PubMed:23857366, ECO:0000269|PubMed:36070373}. 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.ENSP00000357169; -. DR GlyCosmos; Q96P31; 1 site, No reported glycans. DR GlyGen; Q96P31; 1 site. DR iPTMnet; Q96P31; -. DR PhosphoSitePlus; Q96P31; -. DR BioMuta; FCRL3; -. DR DMDM; 74761021; -. DR MassIVE; Q96P31; -. DR PaxDb; 9606-ENSP00000357167; -. DR PeptideAtlas; Q96P31; -. DR ProteomicsDB; 77608; -. [Q96P31-1] DR ProteomicsDB; 77609; -. [Q96P31-2] DR ProteomicsDB; 77610; -. [Q96P31-3] DR ProteomicsDB; 77613; -. [Q96P31-6] DR ProteomicsDB; 77614; -. [Q96P31-7] DR Antibodypedia; 2552; 201 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 AGR; HGNC:18506; -. 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; HEKVYYK; -. DR OrthoDB; 3026247at2759; -. DR PhylomeDB; Q96P31; -. DR TreeFam; TF351107; -. DR PathwayCommons; Q96P31; -. DR SignaLink; Q96P31; -. DR BioGRID-ORCS; 115352; 7 hits in 1138 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 122 other cell types or tissues. DR ExpressionAtlas; Q96P31; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell. 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 GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW. DR CDD; cd00096; Ig; 2. DR Gene3D; 2.60.40.10; Immunoglobulins; 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 PANTHER; PTHR11481:SF112; FC RECEPTOR LIKE 1; 1. DR PANTHER; PTHR11481; IMMUNOGLOBULIN FC RECEPTOR; 1. DR Pfam; PF00047; ig; 2. DR Pfam; PF13895; Ig_2; 2. DR Pfam; PF13927; Ig_3; 1. DR SMART; SM00409; IG; 6. DR SMART; SM00408; IGc2; 5. DR SUPFAM; SSF48726; Immunoglobulin; 6. DR PROSITE; PS50835; IG_LIKE; 6. DR Genevisible; Q96P31; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cell projection; Disulfide bond; KW Fertilization; Glycoprotein; Immunoglobulin domain; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; KW 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 //