Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Fc receptor-like protein 3

Gene

FCRL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation. Enhances activation of NF-kappa-B and MAPK signaling pathways in TLR9 stimulated B-cells (PubMed:23857366). Has inhibitory potentional on B-cell receptor (BCR)-mediated signaling, possibly through association with SH2 domain-containing phosphatases. Inhibits cell tyrosine phosphorylation, calcium mobilization and activation-induced cell death induced through BCR signaling (PubMed:19843936). Regulatory T-cells expressing FCRL3 exhibit a memory phenotype, are relatively nonresponsive to antigenic stimulation in presence of IL2 and have reduced capacity to suppress the proliferation of effector T-cells (PubMed:20190142, PubMed:19494275).4 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB

GO - Biological processi

  • negative regulation of B cell receptor signaling pathway Source: UniProtKB
  • negative regulation of immunoglobulin production Source: UniProtKB
  • positive regulation of B cell proliferation Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • regulation of B cell activation Source: UniProtKB
  • regulation of B cell differentiation Source: UniProtKB
  • regulation of calcium ion import Source: UniProtKB
  • regulation of toll-like receptor 9 signaling pathway Source: UniProtKB

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
Fc receptor-like protein 3Curated
Short name:
FcR-like protein 3Curated
Short name:
FcRL3Curated
Alternative name(s):
Fc receptor homolog 3Curated
Short name:
FcRH3Curated
IFGP family protein 3
Short name:
hIFGP3
Immune receptor translocation-associated protein 3
SH2 domain-containing phosphatase anchor protein 2
CD_antigen: CD307c
Gene namesi
Name:FCRL3Imported
Synonyms:FCRH3Imported, IFGP3Imported, IRTA3Imported, SPAP2Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000160856.20.
HGNCiHGNC:18506. FCRL3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 573ExtracellularSequence analysisAdd BLAST556
Transmembranei574 – 594HelicalSequence analysisAdd BLAST21
Topological domaini595 – 734CytoplasmicSequence analysisAdd BLAST140

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Rheumatoid arthritis (RA)9 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
See also OMIM:180300
Genetic variation in FCRL3 may influence susceptibility to autoimmune disorders, including Graves disease or multiple sclerosis. Graves disease is an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. Multiple sclerosis is an autoimmune/inflammatory neurodegenerative disease which mainly affects young adults and is characterized by destruction of myelin in the central nervous system.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi650Y → F: No effect on inhibition of cell death. No effect on interaction with INPP5D, PTPN6 and PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-662; F-692 and F-722. Alters binding with SYK and ZAP70; when associated with F-662. Decreases calcium influx inhibition; when associated with F-662 and F-722. Decreases calcium influx inhibition; when associated with F-692 and F-722. 2 Publications1
Mutagenesisi662Y → F: Reduces inhibition of cell death. Decreases interaction with INPP5D and PTPN6. No effect on interaction with PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-692 and F-722. Alters binding with SYK and ZAP70; when associated with F-650. Decreases calcium influx inhibition; when associated with F-650 and F-722. Increases calcium influx inhibition; when associated with F-650 and F-722. 2 Publications1
Mutagenesisi692Y → F: Partially reduces inhibition of cell death. Decreases interaction with INPP5D and PTPN11. No effect on interaction with PTPN6. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-662 and F-722. Alters binding with PTPN6 and PTPN11; when associated with F-772. Decreases calcium influx inhibition; when associated with F-650 and F-722. Increases calcium influx inhibition; when associated with F-650 and F-662. Decreases calcium influx inhibition; when associated with F-722. 2 Publications1
Mutagenesisi722Y → F: No effect on inhibition of cell death. No effect on interaction with INPP5D, PTPN6 and PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-662 and F-692. Alters binding with PTPN6 and PTPN11; when associated with F-692. Decreases calcium influx inhibition; when associated with F-650 and F-662. Decreases calcium influx inhibition; when associated with F-650 and F-692. Decreases calcium influx inhibition; when associated with F-692. 2 Publications1

Organism-specific databases

DisGeNETi115352.
MIMi180300. phenotype.
OpenTargetsiENSG00000160856.
PharmGKBiPA142671767.

Polymorphism and mutation databases

BioMutaiFCRL3.
DMDMi74761021.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000033164018 – 734Fc receptor-like protein 3Add BLAST717

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 82PROSITE-ProRule annotation
Disulfide bondi120 ↔ 163PROSITE-ProRule annotation
Disulfide bondi211 ↔ 260PROSITE-ProRule annotation
Disulfide bondi309 ↔ 358PROSITE-ProRule annotation
Disulfide bondi404 ↔ 451PROSITE-ProRule annotation
Disulfide bondi497 ↔ 544PROSITE-ProRule annotation
Glycosylationi561N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei650Phosphotyrosine1 Publication1
Modified residuei662Phosphotyrosine1 Publication1
Modified residuei692Phosphotyrosine1 Publication1
Modified residuei722Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated on cytoplasmic tyrosines; required for interaction with protein tyrosine phosphatases and protein tyrosine kinases.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ96P31.
PeptideAtlasiQ96P31.
PRIDEiQ96P31.

PTM databases

iPTMnetiQ96P31.
PhosphoSitePlusiQ96P31.

Expressioni

Tissue specificityi

Primarily expressed in secondary lymphoid tissues by mature subsets of B-cells. Low expression on transitional B cells which increases to higher surface expression on mature and memory B-cells with innate-like features (at protein level) (PubMed:23857366). Expressed a low levels in naive and germinal center B-cells but also expressed in NK cells (at protein level). Expressed in a population of thymically derived natrurally ocurring regulatory T-cells that exhibits a memory phenotype, specialized in suppressing immune response to self-antigens (PubMed:20190142). Detected in spleen, lymph node, peripheral blood lymphocytes, thymus, bone marrow, kidney, salivary gland, adrenal gland and uterus.7 Publications

Developmental stagei

In B-cells, expression increases as a function of differentiation and peaks on memory B-cells.1 Publication

Gene expression databases

BgeeiENSG00000160856.
ExpressionAtlasiQ96P31. baseline and differential.
GenevisibleiQ96P31. HS.

Organism-specific databases

HPAiHPA015508.

Interactioni

Subunit structurei

Interacts (via phosphorylated ITIM motifs) with phosphatases INPP5D, PTPN6 and PTPN11. Interacts (via ITIM motifs) SYK and ZAP70.2 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi125428. 6 interactors.
STRINGi9606.ENSP00000357167.

Structurei

3D structure databases

ProteinModelPortaliQ96P31.
SMRiQ96P31.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 98Ig-like C2-type 1Add BLAST78
Domaini99 – 182Ig-like C2-type 2Add BLAST84
Domaini192 – 270Ig-like C2-type 3Add BLAST79
Domaini284 – 369Ig-like C2-type 4Add BLAST86
Domaini383 – 470Ig-like C2-type 5Add BLAST88
Domaini476 – 563Ig-like C2-type 6Add BLAST88

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi648 – 653ITIM motif 16
Motifi660 – 665ITIM motif 26
Motifi690 – 695ITIM motif 36
Motifi720 – 725ITIM motif 46

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IH5T. Eukaryota.
ENOG410YF57. LUCA.
GeneTreeiENSGT00760000119130.
HOVERGENiHBG074073.
InParanoidiQ96P31.
KOiK06727.
OMAiTVTFSWH.
OrthoDBiEOG091G03OP.
PhylomeDBiQ96P31.
TreeFamiTF351107.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
PfamiView protein in Pfam
PF00047. ig. 1 hit.
PF13895. Ig_2. 4 hits.
SMARTiView protein in SMART
SM00409. IG. 6 hits.
SM00408. IGc2. 5 hits.
SUPFAMiSSF48726. SSF48726. 6 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 6 hits.

Sequences (7)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96P31-1) [UniParc]FASTAAdd to basket
Also known as: Spap2a

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.

« Hide

        10         20         30         40         50
MLLWLLLLIL TPGREQSGVA PKAVLLLNPP WSTAFKGEKV ALICSSISHS
60 70 80 90 100
LAQGDTYWYH DEKLLKIKHD KIQITEPGNY QCKTRGSSLS DAVHVEFSPD
110 120 130 140 150
WLILQALHPV FEGDNVILRC QGKDNKNTHQ KVYYKDGKQL PNSYNLEKIT
160 170 180 190 200
VNSVSRDNSK YHCTAYRKFY ILDIEVTSKP LNIQVQELFL HPVLRASSST
210 220 230 240 250
PIEGSPMTLT CETQLSPQRP DVQLQFSLFR DSQTLGLGWS RSPRLQIPAM
260 270 280 290 300
WTEDSGSYWC EVETVTHSIK KRSLRSQIRV QRVPVSNVNL EIRPTGGQLI
310 320 330 340 350
EGENMVLICS VAQGSGTVTF SWHKEGRVRS LGRKTQRSLL AELHVLTVKE
360 370 380 390 400
SDAGRYYCAA DNVHSPILST WIRVTVRIPV SHPVLTFRAP RAHTVVGDLL
410 420 430 440 450
ELHCESLRGS PPILYRFYHE DVTLGNSSAP SGGGASFNLS LTAEHSGNYS
460 470 480 490 500
CDADNGLGAQ HSHGVSLRVT VPVSRPVLTL RAPGAQAVVG DLLELHCESL
510 520 530 540 550
RGSFPILYWF YHEDDTLGNI SAHSGGGASF NLSLTTEHSG NYSCEADNGL
560 570 580 590 600
GAQHSKVVTL NVTGTSRNRT GLTAAGITGL VLSILVLAAA AALLHYARAR
610 620 630 640 650
RKPGGLSATG TSSHSPSECQ EPSSSRPSRI DPQEPTHSKP LAPMELEPMY
660 670 680 690 700
SNVNPGDSNP IYSQIWSIQH TKENSANCPM MHQEHEELTV LYSELKKTHP
710 720 730
DDSAGEASSR GRAHEEDDEE NYENVPRVLL ASDH
Length:734
Mass (Da):80,856
Last modified:December 1, 2001 - v1
Checksum:iB3411B73A35EC668
GO
Isoform 2 (identifier: Q96P31-2) [UniParc]FASTAAdd to basket
Also known as: Spap2b

The sequence of this isoform differs from the canonical sequence as follows:
     187-282: ELFLHPVLRA...SLRSQIRVQR → G

Show »
Length:639
Mass (Da):69,929
Checksum:iDEAD7AD4E64CA984
GO
Isoform 3 (identifier: Q96P31-3) [UniParc]FASTAAdd to basket
Also known as: Spap2c

The sequence of this isoform differs from the canonical sequence as follows:
     378-378: I → TLLSPSV

Show »
Length:740
Mass (Da):81,441
Checksum:i038AFA83A2909E46
GO
Isoform 4 (identifier: Q96P31-4) [UniParc]FASTAAdd to basket
Also known as: Spap2d

The sequence of this isoform differs from the canonical sequence as follows:
     187-189: ELF → GNG
     190-734: Missing.

Show »
Length:189
Mass (Da):21,441
Checksum:iE4A4CC249EBC65C9
GO
Isoform 5 (identifier: Q96P31-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     188-199: LFLHPVLRASSS → ARCPAAILPLQR
     200-734: Missing.

Show »
Length:199
Mass (Da):22,632
Checksum:iD51D6112E9DA5603
GO
Isoform 6 (identifier: Q96P31-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     725-734: VPRVLLASDH → ILNPRKNKVQDFPCLCNT

Note: No experimental confirmation available.
Show »
Length:742
Mass (Da):81,853
Checksum:iB0650200E7CA19B8
GO
Isoform 7 (identifier: Q96P31-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     698-707: THPDDSAGEA → EQSSRFSMSL
     708-734: Missing.

Show »
Length:707
Mass (Da):77,921
Checksum:iAC6D131F97359E8E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti244R → K in AK098122 (PubMed:14702039).Curated1
Sequence conflicti653V → A in AAK91779 (PubMed:11493702).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04292428N → D2 PublicationsCorresponds to variant dbSNP:rs7522061Ensembl.1
Natural variantiVAR_042925307L → F. Corresponds to variant dbSNP:rs12041673Ensembl.1
Natural variantiVAR_042926445H → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_042927660P → L. Corresponds to variant dbSNP:rs944627Ensembl.1
Natural variantiVAR_042928721N → S. Corresponds to variant dbSNP:rs2282284Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033300187 – 282ELFLH…IRVQR → G in isoform 2. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_033301187 – 189ELF → GNG in isoform 4. 1 Publication3
Alternative sequenceiVSP_033302188 – 199LFLHP…RASSS → ARCPAAILPLQR in isoform 5. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_033303190 – 734Missing in isoform 4. 1 PublicationAdd BLAST545
Alternative sequenceiVSP_033304200 – 734Missing in isoform 5. 1 PublicationAdd BLAST535
Alternative sequenceiVSP_033305378I → TLLSPSV in isoform 3. 1 Publication1
Alternative sequenceiVSP_033306698 – 707THPDDSAGEA → EQSSRFSMSL in isoform 7. 1 Publication10
Alternative sequenceiVSP_033307708 – 734Missing in isoform 7. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_033308725 – 734VPRVLLASDH → ILNPRKNKVQDFPCLCNT in isoform 6. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY043466 mRNA. Translation: AAK91779.1.
AF416901 mRNA. Translation: AAL13290.1.
AF416902 mRNA. Translation: AAL13291.1.
AF416903 mRNA. Translation: AAL13292.1.
AF416904 mRNA. Translation: AAL13293.1.
AF416905 mRNA. Translation: AAL13294.1.
EF064732 Genomic DNA. Translation: ABK41915.1.
AK098122 mRNA. No translation available.
AL356276 Genomic DNA. Translation: CAH73055.1.
AL356276 Genomic DNA. Translation: CAH73056.1.
AL356276 Genomic DNA. Translation: CAH73058.1.
CH471121 Genomic DNA. Translation: EAW52872.1.
CH471121 Genomic DNA. Translation: EAW52876.1.
CH471121 Genomic DNA. Translation: EAW52877.1.
BC028933 mRNA. Translation: AAH28933.1.
CCDSiCCDS1167.1. [Q96P31-1]
CCDS81385.1. [Q96P31-6]
RefSeqiNP_001307262.1. NM_001320333.1. [Q96P31-6]
NP_443171.2. NM_052939.3. [Q96P31-1]
XP_006711208.1. XM_006711145.1. [Q96P31-1]
UniGeneiHs.292449.

Genome annotation databases

EnsembliENST00000368184; ENSP00000357167; ENSG00000160856. [Q96P31-1]
ENST00000368186; ENSP00000357169; ENSG00000160856. [Q96P31-6]
ENST00000477837; ENSP00000433430; ENSG00000160856. [Q96P31-2]
ENST00000485028; ENSP00000434331; ENSG00000160856. [Q96P31-1]
ENST00000492769; ENSP00000435487; ENSG00000160856. [Q96P31-3]
GeneIDi115352.
KEGGihsa:115352.
UCSCiuc001fqz.5. human. [Q96P31-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFCRL3_HUMAN
AccessioniPrimary (citable) accession number: Q96P31
Secondary accession number(s): A0N0M4
, A8MTH7, D3DVD2, Q5VXZ8, Q8N6S2, Q96LA4, Q96P27, Q96P28, Q96P29, Q96P30
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: December 1, 2001
Last modified: October 25, 2017
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot