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   27-MAR-2024, entry version 176.
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   GlyCosmos; Q96PJ5; 1 site, No reported glycans.
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; 9606-ENSP00000271532; -.
DR   PeptideAtlas; Q96PJ5; -.
DR   Antibodypedia; 34231; 228 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   AGR; HGNC:18507; -.
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; 3026247at2759; -.
DR   PhylomeDB; Q96PJ5; -.
DR   TreeFam; TF351107; -.
DR   PathwayCommons; Q96PJ5; -.
DR   SignaLink; Q96PJ5; -.
DR   BioGRID-ORCS; 83417; 9 hits in 1146 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 35 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; Immunoglobulins; 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   PANTHER; PTHR11481:SF108; FC RECEPTOR-LIKE PROTEIN 4; 1.
DR   PANTHER; PTHR11481; IMMUNOGLOBULIN FC RECEPTOR; 1.
DR   Pfam; PF00047; ig; 1.
DR   Pfam; PF13895; Ig_2; 1.
DR   SMART; SM00409; IG; 4.
DR   SMART; SM00408; IGc2; 4.
DR   SUPFAM; SSF48726; Immunoglobulin; 4.
DR   PROSITE; PS50835; IG_LIKE; 4.
DR   Genevisible; Q96PJ5; HS.
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
//