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HGNC Approved Gene Symbol: FCRL2
Cytogenetic location: 1q23.1 Genomic coordinates (GRCh38) : 1:157,745,733-157,777,132 (from NCBI)
Receptors for the Fc region (FcRs) of immunoglobulins (Igs) modulate cellular and humoral immunity by linking their antibody ligands with effector cells of the immune system. FcRs sense humoral concentrations of antibody, initiate cellular responses in host defense, and participate in autoimmune disorders.
By EST database searching for immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptor proteins, Xu et al. (2001) identified a cDNA encoding SPAP1A (SH2 domain-containing phosphatase anchor protein-1A). The deduced 255-amino acid transmembrane protein contains 2 ITIMs. Further searches and sequencing identified a 192-amino acid splice variant, SPAP1B, lacking the intracellular ITIMs, and a 144-amino acid isoform, SPAP1C, lacking the transmembrane segment. RT-PCR analysis detected SPAP1A expression in spleen, peripheral blood, bone marrow, and B-cell lines, but not in other tissues. SPAP1C was also detected in Jurkat and B-cell lines but SPAP1B was not detected in any samples tested. Western blot analysis showed expression of SPAP1A as a 38- and 40-kD doublet protein reduced to 32 kD or 28 kD by N-glycosidase or O-glycosidase treatment, respectively. Immunoblot analysis indicated that SPAP1A ITIMs recruit the SHP1 (PTPN6; 176883), but not the SHP2 (PTPN11; 176876), tyrosine phosphatase, a major negative regulator of hematopoietic cell signaling.
By database searching using a consensus sequence corresponding to the second Ig-like domains of FCGR1A (146760), FCGR2A (146790), and FCGR3A (146740) as well as the third Ig-like domain of the polymeric Ig receptor (PIGR; 173880), Davis et al. (2001) identified 2 BAC clones located at chromosome 1q21.1-q22. They found that one of these clones contained 3 novel putative Ig superfamily genes, which they designated FCRH1 (606508), FCRH2, and FCRH3 (606510), as well as 2 previously identified members of this family, FCRH4 (IRTA1; 605876) and FCRH5 (IRTA2; 605877). Sequence analysis predicted that the 508-amino acid type I transmembrane protein possesses a hydrophobic signal peptide, 4 extracellular C2 type Ig-like domains, 5 N-linked glycosylation sites, an uncharged transmembrane segment, and an 86-amino acid cytoplasmic tail with 1 ITAM (immunoreceptor tyrosine-based activation motif) and 2 ITIMs. Northern blot analysis revealed expression of approximately 3.0-, 4.4- and 5.5-kb transcripts chiefly in spleen and lymph nodes and a 2.4-kb transcript in kidney. RT-PCR analysis detected expression in mature B-cell lines. Davis et al. (2001) suggested that FCRH2 may have an activating/inhibitory or a fine-tuning role in regulation of immunologic function.
By genomic sequence analysis, Davis et al. (2001) determined that the FCRH2 gene contains 12 exons that span approximately 30 kb.
By BAC and genomic sequence analysis, Davis et al. (2001) mapped the FCRH2 gene to chromosome 1q21.2-q22, near the classic FCGR loci.
Davis, R. S., Wang, Y.-H., Kubagawa, H., Cooper, M. D. Identification of a family of Fc receptor homologs with preferential B cell expression. Proc. Nat. Acad. Sci. 98: 9772-9777, 2001. [PubMed: 11493702] [Full Text: https://doi.org/10.1073/pnas.171308498]
Xu, M., Zhao, R., Zhao, Z. J. Molecular cloning and characterization of SPAP1, an inhibitory receptor. Biochem. Biophys. Res. Commun. 280: 768-775, 2001. [PubMed: 11162587] [Full Text: https://doi.org/10.1006/bbrc.2000.4213]