FCRL4_HUMAN
ID FCRL4_HUMAN Reviewed; 515 AA.
AC Q96PJ5; Q96PJ3; Q96RE0;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Fc receptor-like protein 4;
DE Short=FcR-like protein 4;
DE Short=FcRL4;
DE AltName: Full=Fc receptor homolog 4;
DE Short=FcRH4;
DE AltName: Full=IFGP family protein 2;
DE Short=hIFGP2;
DE AltName: Full=Immune receptor translocation-associated protein 1;
DE AltName: CD_antigen=CD307d;
DE Flags: Precursor;
GN Name=FCRL4; Synonyms=FCRH4, IFGP2, IRTA1;
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), TISSUE SPECIFICITY, CHROMOSOMAL
RP TRANSLOCATION WITH IGHA1, AND INVOLVEMENT IN MM.
RC TISSUE=Spleen;
RX PubMed=11290337; DOI=10.1016/s1074-7613(01)00109-1;
RA Hatzivassiliou G., Miller I., Takizawa J., Palanisamy N., Rao P.H.,
RA Iida S., Tagawa S., Taniwaki M., Russo J., Neri A., Cattoretti G.,
RA Clynes R., Mendelsohn C., Chaganti R.S.K., Dalla-Favera R.;
RT "IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B
RT cells and involved in chromosome 1q21 abnormalities in B cell malignancy.";
RL Immunity 14:277-289(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [MRNA] OF
RP 88-515 (ISOFORM 2).
RC TISSUE=Tonsil;
RX PubMed=12037601; DOI=10.1007/s00251-002-0436-x;
RA Guselnikov S.V., Ershova S.A., Mechetina L.V., Najakshin A.M.,
RA Volkova O.Y., Alabyev B.Y., Taranin A.V.;
RT "A family of highly diverse human and mouse genes structurally links
RT leukocyte FcR, gp42 and PECAM-1.";
RL Immunogenetics 54:87-95(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=12881317; DOI=10.1182/blood-2003-03-0750;
RA Falini B., Tiacci E., Pucciarini A., Bigerna B., Kurth J.,
RA Hatzivassiliou G., Droetto S., Galletti B.V., Gambacorta M., Orazi A.,
RA Pasqualucci L., Miller I., Kueppers R., Dalla-Favera R., Cattoretti G.;
RT "Expression of the IRTA1 receptor identifies intraepithelial and
RT subepithelial marginal zone B cells of the mucosa-associated lymphoid
RT tissue (MALT).";
RL Blood 102:3684-3692(2003).
RN [9]
RP CHROMOSOMAL TRANSLOCATION, AND INVOLVEMENT IN NHG.
RX PubMed=12619161; DOI=10.1002/gcc.10181;
RA Lestou V.S., Ludkovski O., Connors J.M., Gascoyne R.D., Lam W.L.,
RA Horsman D.E.;
RT "Characterization of the recurrent translocation t(1;1)(p36.3;q21.1-2) in
RT non-Hodgkin lymphoma by multicolor banding and fluorescence in situ
RT hybridization analysis.";
RL Genes Chromosomes Cancer 36:375-381(2003).
RN [10]
RP FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF TYR-451; TYR-463 AND TYR-493, AND
RP INTERACTION WITH PTPN6 AND PTPN11.
RX PubMed=14597715; DOI=10.1073/pnas.1935944100;
RA Ehrhardt G.R.A., Davis R.S., Hsu J.T., Leu C.-M., Ehrhardt A., Cooper M.D.;
RT "The inhibitory potential of Fc receptor homolog 4 on memory B cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13489-13494(2003).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=16079106;
RA Joehrens K., Shimizu Y., Anagnostopoulos I., Schiffmann S., Tiacci E.,
RA Falini B., Stein H.;
RT "T-bet-positive and IRTA1-positive monocytoid B cells differ from marginal
RT zone B cells and epithelial-associated B cells in their antigen profile and
RT topographical distribution.";
RL Haematologica 90:1070-1077(2005).
RN [12]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16157685; DOI=10.1084/jem.20050879;
RA Ehrhardt G.R.A., Hsu J.T., Gartland L., Leu C.-M., Zhang S., Davis R.S.,
RA Cooper M.D.;
RT "Expression of the immunoregulatory molecule FcRH4 defines a distinctive
RT tissue-based population of memory B cells.";
RL J. Exp. Med. 202:783-791(2005).
RN [13]
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).
CC -!- FUNCTION: May function as an inhibitor of the B-cell receptor
CC signaling. May function in the B-cell-mediated immune response.
CC {ECO:0000269|PubMed:14597715}.
CC -!- SUBUNIT: Interacts with PTPN6 and PTPN11.
CC {ECO:0000269|PubMed:14597715}.
CC -!- INTERACTION:
CC Q96PJ5; O95393: BMP10; NbExp=3; IntAct=EBI-4314687, EBI-3922513;
CC Q96PJ5; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-4314687, EBI-398977;
CC Q96PJ5; Q86UW9: DTX2; NbExp=3; IntAct=EBI-4314687, EBI-740376;
CC Q96PJ5; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-4314687, EBI-10266796;
CC Q96PJ5; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-4314687, EBI-10317425;
CC Q96PJ5; P04155: TFF1; NbExp=3; IntAct=EBI-4314687, EBI-743871;
CC Q96PJ5; Q03403: TFF2; NbExp=3; IntAct=EBI-4314687, EBI-4314702;
CC Q96PJ5; P36508: ZNF76; NbExp=3; IntAct=EBI-4314687, EBI-7254550;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16157685,
CC ECO:0000269|PubMed:16849395}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:16157685, ECO:0000269|PubMed:16849395}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96PJ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PJ5-2; Sequence=VSP_033310;
CC -!- TISSUE SPECIFICITY: Specifically expressed by memory and monocytoid B-
CC cells which populate spleen and lymph nodes. Preferentially expressed
CC in memory B-cells associated with mucosal tissue (at protein level).
CC {ECO:0000269|PubMed:11290337, ECO:0000269|PubMed:11929751,
CC ECO:0000269|PubMed:12881317, ECO:0000269|PubMed:16079106,
CC ECO:0000269|PubMed:16157685, ECO:0000269|PubMed:16849395}.
CC -!- PTM: Phosphorylated on cytoplasmic tyrosines upon activation.
CC {ECO:0000269|PubMed:14597715}.
CC -!- DISEASE: Note=A chromosomal aberration involving FCRL4 is found in non-
CC Hodgkin lymphoma (NHG). Translocation t(1;1)(p36.3; q21.1-2).
CC {ECO:0000269|PubMed:12619161}.
CC -!- DISEASE: Note=A chromosomal aberration involving FCRL4 is found in
CC multiple myeloma (MM). Translocation t(1;14)(q21;q32) that forms a
CC FCRL4-IGHA1 fusion protein. {ECO:0000269|PubMed:11290337}.
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DR EMBL; AF343659; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF397452; AAK93970.1; -; mRNA.
DR EMBL; AF329490; AAL23900.1; -; mRNA.
DR EMBL; AF329492; AAL23902.1; -; mRNA.
DR EMBL; EF064731; ABK41914.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52883.1; -; Genomic_DNA.
DR EMBL; BC125173; AAI25174.1; -; mRNA.
DR EMBL; BC125174; AAI25175.1; -; mRNA.
DR CCDS; CCDS1166.1; -. [Q96PJ5-1]
DR RefSeq; NP_112572.1; NM_031282.2. [Q96PJ5-1]
DR AlphaFoldDB; Q96PJ5; -.
DR SMR; Q96PJ5; -.
DR BioGRID; 123641; 44.
DR IntAct; Q96PJ5; 11.
DR STRING; 9606.ENSP00000271532; -.
DR GlyGen; Q96PJ5; 1 site.
DR iPTMnet; Q96PJ5; -.
DR PhosphoSitePlus; Q96PJ5; -.
DR SwissPalm; Q96PJ5; -.
DR BioMuta; FCRL4; -.
DR DMDM; 74761029; -.
DR MassIVE; Q96PJ5; -.
DR PaxDb; Q96PJ5; -.
DR PeptideAtlas; Q96PJ5; -.
DR PRIDE; Q96PJ5; -.
DR Antibodypedia; 34231; 209 antibodies from 26 providers.
DR DNASU; 83417; -.
DR Ensembl; ENST00000271532.2; ENSP00000271532.1; ENSG00000163518.11. [Q96PJ5-1]
DR GeneID; 83417; -.
DR KEGG; hsa:83417; -.
DR MANE-Select; ENST00000271532.2; ENSP00000271532.1; NM_031282.3; NP_112572.1.
DR UCSC; uc001fqw.3; human. [Q96PJ5-1]
DR CTD; 83417; -.
DR DisGeNET; 83417; -.
DR GeneCards; FCRL4; -.
DR HGNC; HGNC:18507; FCRL4.
DR HPA; ENSG00000163518; Tissue enriched (lymphoid).
DR MIM; 605876; gene.
DR neXtProt; NX_Q96PJ5; -.
DR OpenTargets; ENSG00000163518; -.
DR PharmGKB; PA142671768; -.
DR VEuPathDB; HostDB:ENSG00000163518; -.
DR eggNOG; ENOG502S65W; Eukaryota.
DR GeneTree; ENSGT01050000244808; -.
DR HOGENOM; CLU_023383_7_1_1; -.
DR InParanoid; Q96PJ5; -.
DR OMA; YQHYWRE; -.
DR OrthoDB; 53940at2759; -.
DR PhylomeDB; Q96PJ5; -.
DR TreeFam; TF351107; -.
DR PathwayCommons; Q96PJ5; -.
DR SignaLink; Q96PJ5; -.
DR BioGRID-ORCS; 83417; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; FCRL4; human.
DR GeneWiki; FCRL4; -.
DR GenomeRNAi; 83417; -.
DR Pharos; Q96PJ5; Tbio.
DR PRO; PR:Q96PJ5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96PJ5; protein.
DR Bgee; ENSG00000163518; Expressed in buccal mucosa cell and 38 other tissues.
DR Genevisible; Q96PJ5; 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:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 4.
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; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 4.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 4.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane;
KW Chromosomal rearrangement; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..515
FT /note="Fc receptor-like protein 4"
FT /id="PRO_0000331642"
FT TOPO_DOM 20..387
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 388..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 23..97
FT /note="Ig-like C2-type 1"
FT DOMAIN 102..183
FT /note="Ig-like C2-type 2"
FT DOMAIN 193..271
FT /note="Ig-like C2-type 3"
FT DOMAIN 275..374
FT /note="Ig-like C2-type 4"
FT REGION 494..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 449..454
FT /note="ITIM motif 1"
FT MOTIF 461..466
FT /note="ITIM motif 2"
FT MOTIF 491..496
FT /note="ITIM motif 3"
FT SITE 17..18
FT /note="Breakpoint for insertion to form FCRL4-IGHA1 fusion
FT protein"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 123..167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 212..261
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 310..359
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 454..515
FT /note="VHPKKGDLVYSEIQTTQLGEEEEANTSRTLLEDKDVSVVYSEVKTQHPDNSA
FT GKISSKDEES -> GEDSLLGSCSWPQPWKDNALSALGNAPGLPKVSQIQIFPDIMCPR
FT RVEMMLRKRHL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12037601"
FT /id="VSP_033310"
FT VARIANT 60
FT /note="R -> Q (in dbSNP:rs11582663)"
FT /id="VAR_042929"
FT VARIANT 255
FT /note="N -> S (in dbSNP:rs4561035)"
FT /id="VAR_042930"
FT VARIANT 457
FT /note="K -> R (in dbSNP:rs2039401)"
FT /id="VAR_042931"
FT VARIANT 493
FT /note="Y -> C (in dbSNP:rs3811028)"
FT /id="VAR_042932"
FT MUTAGEN 451
FT /note="Y->F: No effect on function, phosphorylation and
FT interaction with PTPN6 and PTPN11."
FT /evidence="ECO:0000269|PubMed:14597715"
FT MUTAGEN 463
FT /note="Y->F: Loss of function, phosphorylation and
FT interaction with PTPN6 and PTPN11."
FT /evidence="ECO:0000269|PubMed:14597715"
FT MUTAGEN 493
FT /note="Y->F: Loss of interaction with PTPN6 and PTPN11 and
FT partial loss of function and phosphorylation."
FT /evidence="ECO:0000269|PubMed:14597715"
FT CONFLICT 179
FT /note="S -> L (in Ref. 2; AAK93970)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 57224 MW; F3B7AD14FB1B449A CRC64;
MLLWASLLAF APVCGQSAAA HKPVISVHPP WTTFFKGERV TLTCNGFQFY ATEKTTWYHR
HYWGEKLTLT PGNTLEVRES GLYRCQARGS PRSNPVRLLF SSDSLILQAP YSVFEGDTLV
LRCHRRRKEK LTAVKYTWNG NILSISNKSW DLLIPQASSN NNGNYRCIGY GDENDVFRSN
FKIIKIQELF PHPELKATDS QPTEGNSVNL SCETQLPPER SDTPLHFNFF RDGEVILSDW
STYPELQLPT VWRENSGSYW CGAETVRGNI HKHSPSLQIH VQRIPVSGVL LETQPSGGQA
VEGEMLVLVC SVAEGTGDTT FSWHREDMQE SLGRKTQRSL RAELELPAIR QSHAGGYYCT
ADNSYGPVQS MVLNVTVRET PGNRDGLVAA GATGGLLSAL LLAVALLFHC WRRRKSGVGF
LGDETRLPPA PGPGESSHSI CPAQVELQSL YVDVHPKKGD LVYSEIQTTQ LGEEEEANTS
RTLLEDKDVS VVYSEVKTQH PDNSAGKISS KDEES
