Alternative titles; symbols
HGNC Approved Gene Symbol: TREML1
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38) : 6:41,149,260-41,155,403 (from NCBI)
TREML1 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (605085) and TREM2 (605086), but it has distinct structural and functional properties. TREML1 enhances calcium signaling in an SHP2 (PTPN11; 176876)-dependent manner (Allcock et al., 2003; Barrow et al., 2004).
Washington et al. (2002) cloned and characterized mouse Treml1, which they called Tlt1. By sequence analysis they identified human TLT1, which encodes a 312-amino acid protein. TLT1 has an N-terminal leader sequence, followed by an IgV domain, a transmembrane domain, a polyproline-rich region, and an immunoreceptor tyrosine-based inhibitory motif (ITIM).
Allcock et al. (2003) constructed overlapping BAC/PAC clones from the TREM gene cluster on chromosome 6 and identified 3 complete Ig superfamily genes that they called TLT1, TLT2 (TREML2; 609715), and TLT3 (TREML3; 609716). They obtained a full-length TLT1 cDNA by PCR of monocyte cell line mRNA and 5-prime RACE. TLT1 has a calculated molecular mass of 33 kD. Unlike other TREM proteins, the IgV domain of TLT1 has no potential N-glycosylation sites. The transmembrane domain of TLT1 lacks charged residues, and the 127-amino acid cytoplasmic region has 2 tyr residues (Y245 and Y281), each in an ITIM. Allcock et al. (2003) also cloned a TLT1 splice variant lacking exon 5. They predicted that the truncation results in a membrane-bound form of TLT1 lacking the ITIMs. RT-PCR analysis detected weak expression of TLT1 in monocyte, B-cell, and T-cell lines. TLT1 expression could be upregulated by mitogen stimulation.
Barrow et al. (2004) noted that the short TLT1 splice variant encodes a 199-amino acid protein that differs from the full-length isoform in its cytoplasmic domain, which contains only 14 residues. Western blot analysis detected full-length TLT1 as a 35-kD protein and the short TLT1 isoform as a 20-kD protein in peripheral blood lymphocytes.
Using flow cytometry and confocal microscopy, Barrow et al. (2004) found that both TLT1 isoforms colocalized with CD62P (SELP; 173610) in alpha granules of resting platelets and, after platelet activation, were expressed with CD62P on the cell surface. Immunoprecipitation analysis of transfected cells showed interaction of TLT1 with SHP2 only in cells expressing the C-terminal classical ITIM of TLT1, Y281; no interaction occurred in cells expressing the nonclassical ITIM, Y245. The SHP2-Y281 ITIM interaction in turn led to enhanced FCER1 (see 147140)-mediated calcium signaling.
By genomic sequence analysis, Allcock et al. (2003) determined that all genes in the TREM cluster have an exon encoding the 5-prime UTR and leader peptide, a second exon encoding the IgV domain, and a variable number of downstream exons encoding the stalk, transmembrane, and cytoplasmic regions. TLT1 contains 6 exons. Exon 5 is subject to alternative splicing.
By genomic sequence analysis, Washington et al. (2002) and Allcock et al. (2003) mapped the TREML1 gene to chromosome 6p21.1, telomeric to the TREM2 gene within the TREM gene cluster. The mouse Treml1 gene maps to chromosome 17 in a region that shows homology of synteny to human chromosome 6.
Allcock, R. J. N., Barrow, A. D., Forbes, S., Beck, S., Trowsdale, J. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Europ. J. Immun. 33: 567-577, 2003. [PubMed: 12645956] [Full Text: https://doi.org/10.1002/immu.200310033]
Barrow, A. D., Astoul, E., Floto, A., Brooke, G., Relou, I. A. M., Jennings, N. S., Smith, K. G. C., Ouwehand, W., Farndale, R. W., Alexander, D. R., Trowsdale, J. Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2. J. Immun. 172: 5838-5842, 2004. [PubMed: 15128762] [Full Text: https://doi.org/10.4049/jimmunol.172.10.5838]
Washington, A. V., Quigley, L., McVicar, D. W. Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster. Blood 100: 3822-3824, 2002. [PubMed: 12393607] [Full Text: https://doi.org/10.1182/blood-2002-02-0523]