Reviewed, UniProtKB/Swiss-Prot Q96PJ5 (FCRL4_HUMAN)

Names and origin

Protein names

Recommended name:
    Fc receptor-like protein 4
      Short name=FcR-like protein 4
      Short name=FcRL4
Alternative name(s):
    Fc receptor homolog 4
      Short name=FcRH4
    IFGP family protein 2
      Short name=hIFGP2
    Immune receptor translocation-associated protein 1

Gene names

Name:	FCRL4
Synonyms:	FCRH4, IFGP2, IRTA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	515 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May function as an inhibitor of the B cell receptor signaling. May function in the B cell-mediated immune response. Ref.10
Subcellular location	Cell membrane; Single-pass type I membrane protein. Ref.12 Ref.13
Tissue specificity	Specifically expressed by memory and monocytoid B cells which populate spleen and lymph nodes. Preferentially expressed in memory B cells associated with mucosal tissue (at protein level). Ref.12 Ref.13 Ref.1 Ref.7 Ref.8 Ref.11
Post-translational modification	Phosphorylated on cytoplasmic tyrosines upon activation. Ref.10
Involvement in disease	A chromosomal aberration involving FCRL4 is found in non-Hodgkin lymphoma (NHG). Translocation t(1;1)(p36.3; q21.1-2). A chromosomal aberration involving FCRL4 is found in multiple myeloma (MM). Translocation t(1;14)(q21;q32) that forms a FCRL4-IGHA1 fusion protein.
Sequence similarities	Contains 4 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Immune response
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96PJ5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96PJ5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     454-515: VHPKKGDLVY...GKISSKDEES → GEDSLLGSCS...VEMMLRKRHL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 515	496	Fc receptor-like protein 4		PRO_0000331642
Regions
	Topological domain	20 – 387	368	Extracellular Potential
	Transmembrane	388 – 408	21	Potential
	Topological domain	409 – 515	107	Cytoplasmic Potential
	Domain	23 – 97	75	Ig-like C2-type 1
	Domain	102 – 183	82	Ig-like C2-type 2
	Domain	193 – 271	79	Ig-like C2-type 3
	Domain	275 – 374	100	Ig-like C2-type 4
	Motif	449 – 454	6	ITIM motif 1
	Motif	461 – 466	6	ITIM motif 2
	Motif	491 – 496	6	ITIM motif 3
Sites
	Site	17 – 18	2	Breakpoint for insertion to form FCRL4-IGHA1 fusion protein
Amino acid modifications
	Glycosylation	374	1	N-linked (GlcNAc...) Potential
	Disulfide bond	44 ↔ 85		By similarity
	Disulfide bond	123 ↔ 167		By similarity
	Disulfide bond	212 ↔ 261		By similarity
	Disulfide bond	310 ↔ 359		By similarity
Natural variations
	Alternative sequence	454 – 515	62	VHPKK…KDEES → GEDSLLGSCSWPQPWKDNAL SALGNAPGLPKVSQIQIFPD IMCPRRVEMMLRKRHL in isoform 2.		VSP_033310
	Natural variant	60	1	R → Q: dbSNP rs11582663.		VAR_042929
	Natural variant	255	1	N → S: dbSNP rs4561035.		VAR_042930
	Natural variant	457	1	K → R: dbSNP rs2039401.		VAR_042931
	Natural variant	493	1	Y → C: dbSNP rs3811028.		VAR_042932
Experimental info
	Mutagenesis	451	1	Y → F: No effect on function, phosphorylation and interaction with PTPN6 and PTPN11. Ref.10
	Mutagenesis	463	1	Y → F: Loss of function, phosphorylation and interaction with PTPN6 and PTPN11. Ref.10
	Mutagenesis	493	1	Y → F: Loss of interaction with PTPN6 and PTPN11 and partial loss of function and phosphorylation. Ref.10
	Sequence conflict	179	1	S → L in AAK93970. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F3B7AD14FB1B449A	FASTA	515	57,224
	10 20 30 40 50 60 MLLWASLLAF APVCGQSAAA HKPVISVHPP WTTFFKGERV TLTCNGFQFY ATEKTTWYHR 70 80 90 100 110 120 HYWGEKLTLT PGNTLEVRES GLYRCQARGS PRSNPVRLLF SSDSLILQAP YSVFEGDTLV 130 140 150 160 170 180 LRCHRRRKEK LTAVKYTWNG NILSISNKSW DLLIPQASSN NNGNYRCIGY GDENDVFRSN 190 200 210 220 230 240 FKIIKIQELF PHPELKATDS QPTEGNSVNL SCETQLPPER SDTPLHFNFF RDGEVILSDW 250 260 270 280 290 300 STYPELQLPT VWRENSGSYW CGAETVRGNI HKHSPSLQIH VQRIPVSGVL LETQPSGGQA 310 320 330 340 350 360 VEGEMLVLVC SVAEGTGDTT FSWHREDMQE SLGRKTQRSL RAELELPAIR QSHAGGYYCT 370 380 390 400 410 420 ADNSYGPVQS MVLNVTVRET PGNRDGLVAA GATGGLLSAL LLAVALLFHC WRRRKSGVGF 430 440 450 460 470 480 LGDETRLPPA PGPGESSHSI CPAQVELQSL YVDVHPKKGD LVYSEIQTTQ LGEEEEANTS 490 500 510 RTLLEDKDVS VVYSEVKTQH PDNSAGKISS KDEES
	Isoform 2. Checksum: 2810BA15A2BA5405	FASTA	509	56,636
	10 20 30 40 50 60 MLLWASLLAF APVCGQSAAA HKPVISVHPP WTTFFKGERV TLTCNGFQFY ATEKTTWYHR 70 80 90 100 110 120 HYWGEKLTLT PGNTLEVRES GLYRCQARGS PRSNPVRLLF SSDSLILQAP YSVFEGDTLV 130 140 150 160 170 180 LRCHRRRKEK LTAVKYTWNG NILSISNKSW DLLIPQASSN NNGNYRCIGY GDENDVFRSN 190 200 210 220 230 240 FKIIKIQELF PHPELKATDS QPTEGNSVNL SCETQLPPER SDTPLHFNFF RDGEVILSDW 250 260 270 280 290 300 STYPELQLPT VWRENSGSYW CGAETVRGNI HKHSPSLQIH VQRIPVSGVL LETQPSGGQA 310 320 330 340 350 360 VEGEMLVLVC SVAEGTGDTT FSWHREDMQE SLGRKTQRSL RAELELPAIR QSHAGGYYCT 370 380 390 400 410 420 ADNSYGPVQS MVLNVTVRET PGNRDGLVAA GATGGLLSAL LLAVALLFHC WRRRKSGVGF 430 440 450 460 470 480 LGDETRLPPA PGPGESSHSI CPAQVELQSL YVDGEDSLLG SCSWPQPWKD NALSALGNAP 490 500 GLPKVSQIQI FPDIMCPRRV EMMLRKRHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy." Hatzivassiliou G., Miller I., Takizawa J., Palanisamy N., Rao P.H., Iida S., Tagawa S., Taniwaki M., Russo J., Neri A., Cattoretti G., Clynes R., Mendelsohn C., Chaganti R.S.K., Dalla-Favera R. Immunity 14:277-289(2001) [PubMed: 11290337] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH IGHA1. Tissue: Spleen.
[2]	"Identification of a family of Fc receptor homologs with preferential B cell expression." Davis R.S., Wang Y.-H., Kubagawa H., Cooper M.D. Proc. Natl. Acad. Sci. U.S.A. 98:9772-9777(2001) [PubMed: 11493702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lymph node.
[3]	"A family of highly diverse human and mouse genes structurally links leukocyte FcR, gp42 and PECAM-1." Guselnikov S.V., Ershova S.A., Mechetina L.V., Najakshin A.M., Volkova O.Y., Alabyev B.Y., Taranin A.V. Immunogenetics 54:87-95(2002) [PubMed: 12037601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 88-515 (ISOFORM 2). Tissue: Tonsil.
[4]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"IRTAs: a new family of immunoglobulin-like receptors differentially expressed in B cells." Miller I., Hatzivassiliou G., Cattoretti G., Mendelsohn C., Dalla-Favera R. Blood 99:2662-2669(2002) [PubMed: 11929751] [Abstract] Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.
[8]	"Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)." Falini B., Tiacci E., Pucciarini A., Bigerna B., Kurth J., Hatzivassiliou G., Droetto S., Galletti B.V., Gambacorta M., Orazi A., Pasqualucci L., Miller I., Kueppers R., Dalla-Favera R., Cattoretti G. Blood 102:3684-3692(2003) [PubMed: 12881317] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Characterization of the recurrent translocation t(1;1)(p36.3;q21.1-2) in non-Hodgkin lymphoma by multicolor banding and fluorescence in situ hybridization analysis." Lestou V.S., Ludkovski O., Connors J.M., Gascoyne R.D., Lam W.L., Horsman D.E. Genes Chromosomes Cancer 36:375-381(2003) [PubMed: 12619161] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION.
[10]	"The inhibitory potential of Fc receptor homolog 4 on memory B cells." Ehrhardt G.R.A., Davis R.S., Hsu J.T., Leu C.-M., Ehrhardt A., Cooper M.D. Proc. Natl. Acad. Sci. U.S.A. 100:13489-13494(2003) [PubMed: 14597715] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF TYR-451; TYR-463 AND TYR-493, INTERACTION WITH PTPN6 AND PTPN11.
[11]	"T-bet-positive and IRTA1-positive monocytoid B cells differ from marginal zone B cells and epithelial-associated B cells in their antigen profile and topographical distribution." Joehrens K., Shimizu Y., Anagnostopoulos I., Schiffmann S., Tiacci E., Falini B., Stein H. Haematologica 90:1070-1077(2005) [PubMed: 16079106] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells." Ehrhardt G.R.A., Hsu J.T., Gartland L., Leu C.-M., Zhang S., Davis R.S., Cooper M.D. J. Exp. Med. 202:783-791(2005) [PubMed: 16157685] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]	"Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia." Polson A.G., Zheng B., Elkins K., Chang W., Du C., Dowd P., Yen L., Tan C., Hongo J.-A., Koeppen H., Ebens A. Int. Immunol. 18:1363-1373(2006) [PubMed: 16849395] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF343659 mRNA. No translation available. AF397452 mRNA. Translation: AAK93970.1. AF329490 mRNA. Translation: AAL23900.1. AF329492 mRNA. Translation: AAL23902.1. EF064731 Genomic DNA. Translation: ABK41914.1. CH471121 Genomic DNA. Translation: EAW52883.1. BC125173 mRNA. Translation: AAI25174.1. BC125174 mRNA. Translation: AAI25175.1.
IPI	IPI00044510. IPI00890728.
RefSeq	NP_112572.1.
UniGene	Hs.120260
3D structure databases
HSSP	HSSP built from PDB template 1F2Q based on UniProtKB P12319.
ModBase	Search...
Proteomic databases
PRIDE	Q96PJ5.
Genome annotation databases
Ensembl	ENSG00000163518. Homo sapiens. [Contig view]
GeneID	83417.
KEGG	hsa:83417.
Organism-specific databases
GeneCards	GC01M155811.
HGNC	HGNC:18507. FCRL4.
MIM	605876. gene.
PharmGKB	PA142671768.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q96PJ5.
HOVERGEN	Q96PJ5.
OMA	Q96PJ5. VKYTWNG.
Gene expression databases
ArrayExpress	Q96PJ5.
Bgee	Q96PJ5.
CleanEx	HS_FCRL4.
Family and domain databases
InterPro	IPR013151. Ig. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003598. Ig_sub2. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 4 hits.
Pfam	PF00047. ig. 3 hits. [Graphical view]
SMART	SM00409. IG. 3 hits. SM00408. IGc2. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 4 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	72310.
SOURCE	Search...

Entry information

Entry name

FCRL4_HUMAN

Accession

Primary (citable) accession number: Q96PJ5
Secondary accession number(s): Q96PJ3, Q96RE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)